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Effect of pH on ammonia production by renal mitochondria

Tannen, Kunin — 1976-12-01

NH3 production by renal cortical mitochondria was studied under conditions of metabolic acidosis induced in vivo and with pH manipulations of the media bathing mitochondria from normal rats. A HCO3- medium equilibrated with O2 and CO2 was utilized with glutamine concentrations of either 10 or 0.5 mM. With chronic acidosis NH3 production increased significantly at either substrate concentration. Similar results were obtained with rotenone in the media, both with chronic acidosis and with acidosis of 3 h duration, indicating that increased glutamine entry and/or phosphate-dependent glutaminase (PDG) activity accounts for the increased ammoniagenesis. In contrast to acidosis induced in vivo, mitochondria from normal rats subjected to a diminution in medium pH, either by manipulation of HCO3 concentration or PCO2, significantly decrease NH3 production. Mitochondrial studies with rotenone, as well as studies of solubilized PDG, suggest that a low pH diminishes NH3 production by directly altering PDG activity. Furthermore, regardless of the specifics of the mechanism, these studies indicate that adaptation to metabolic acidosis is not the immediate, direct result of a change in pH.

Persistence of febrile response to pyrogens after PO/AH lesions in squirrel monkeys

Lipton, Trzcinka — 1976-12-01

Observation of a patient who developed fever in spite of severe CNS sarcoidosis led us to test the idea that febrile responses require mediation by neurons in the preoptic/anterior hypothalamic (PO/AH) region. Changes in rectal and skin temperatures and oxygen consumption were recorded after intravenous and intracerebroventricular injections of endotoxin, after intracerebroventricular prostaglandin E1 (PGE1), and after intravenous injections of leukocyte pyrogens in animals in which the PO/AH region had been destroyed. The capacity to develop fever persisted after PO/AH destruction, and the patterns of heat production and heat loss were unchanged. Pyrogens were still effective after intracerebroventricular 6-hydroxydopamine and intraperitoneal reserpine given to reduce brain amines in monkeys with PO/AH lesions. It is unlikely that a secondary control in the medulla oblongata is responsible for the persisting sensitivity to pyrogens, since multiple injections of endotoxin into this region did not cause fever either before or after the PO/AH region was destroyed. The results do not support the idea that control of fever is localized in the PO/AH region alone. Rather, it appears that in the brains of primates there is either multiple central representation of fever control or an inherent capacity to develop sensitivity to pyrogens and to produce coordinated febrile responses.

Ionic pathways of secretory membrane of frog gastric mucosa in Cl--free media

Holloman, Schwartz, Dinno, Carrasquer — 1976-12-01

Experiments were performed to determine the return ionic pathways of the secretory membrane of frog gastric mucosa associated with the electrogenic H+ pump in Cl--free media. The replacement of a 52 mM Na2SO4 secretory solution with a 52 mM K2SO4 secretory solution led to a decrease of resistance, an increase of the H+ secretory rate, and a reversal of the PD. The replacement of 52 mM Na2SO4 with 52 mM MgSO4 led to an increase of resistance and a decrease of the H+ rate. These results provided evidence for the existence of K+ and Na+ pathways, the former having a lower resistance than the latter. Short-circuiting the mucosa in Mg2+ solutions increased the H+ rate to the value in Na+ solutions, hence ruling out the possibility that Mg2+ might interfere with the H+ pump. The fact that the Mg2+ secretory solution, without K+ or Na+, did not abolish the H+ rate suggested the presence of at least a third ionic pathway. presumably SO42-, providing that Mg2+ does not penetrate the mucosa.

Glycogen levels and peripheral mechanisms of glucose-induced spppression of feeding

VanderWeele, Skoog, Novin — 1976-12-01

Rabbits deprived of food for 0, 2, 4, 6, 8, 16, and 24 h were assessed for glucose-induced feeding suppression, refeeding after deprivation, and liver glycogen. In previous research, we hypothesized a relationship between liver glycogen and the transition from duodenal to hepatic glucose suppression. In duodenally cannulated rabbits, the infusion of 10 ml of isotonic glucose in awake, free-feeding animals significantly suppressed food intake but did not do so in those food deprived for 2, 4, 6, 8, or 24 h. In hepatic-cannulated rabbits, similar amounts of glucose significantly suppressed food intake in 4-, 6-, 16-, and 24-h-deprived animals. Also, refeeding after deprivation increased as a function of continued deprivation until 6 or 8 h, when refeeding reached asymptote, or decreased through 24-h deprivations. In agreement with these observations, liver glycogen showed a sharp decline between 4, 6, and 8 h of deprivation (depending on circadian cycle). It is proposed that liver glycogen depletion, or some correlate, alters liver glucostatic regulation and determines refeeding after deprivation.

Inhibition of transmembrane K transfer in ureter-ligated dogs infused with KCl

Hiatt, Chapman, Davidson, Sheinkopf, Miller — 1976-12-01

In anuric dogs loaded with K by infusion with 2 meq KCl/kg per h until prelethal hyperkalemic cardiotoxicity appears, the extent of transmembrane K transfer depends on the origin of the anuria. Animals with bilateral ureter ligation transfer a mean of 1.2 meq/kg to intracellular fluid, while those with bilateral nephrectomy transfer more than 2.5 times as much (3.1 meq/kg). Further, if dogs with functioning kidneys are ureter ligated or nephrectomized after approximately 45 min of K loading, K transfer ultimately falls as infusion continues. The fall is precipitate and over 90% in ligated animals; but it is gradual, and only 10% in those that are nephrectomized. Finally, K transfer, because of the absence of insulin, is negligible in K-loaded pancreatectomized dogs with bilateral ureter ligation, but fairly substantial in pancreatectomized animals with bilateral nephrectomy. The data suggest that ureter ligation and hyperkalemia activate a renal mechanism that interferes with the transfer of infused K to intracellular fluid. The mechanism may involve the renin-angiotensin II-aldosterone system to a limited degree.

Washout kinetics of red cells and plasma from the spleen

Levesque, Groom — 1976-12-01

Radioiodinated (125I) serum albumin was injected inttravenously in cats and allowed to equilibrate in the circulation. Red cell and plasma washout from the isolated spleens were enrom the isolated spleens were then compared during perfusion with oxygenated Ringer solution, the respective concentrations in the outflow being measured by celloscope and scintillation counters. Washout kinetics yielded three exponential components for cells (perfusate volumes for 50% washout (V1/2) being 0.067, 4.70, and 97 ml/g spleen) but only two for plasm (V1/2, 0.14 and 2.40 ml/g). There is no plasma counterpart to the slowly released cells, i.e., they do not represent a separate vascular space. This is an accord with a previous view that these are immature cells, delayed through adherence to fine structures of the red pulp. Compartment analysis indicates that the plasma and two remaining cell components represent washout from two separate vascular spaces, containing 0.09 ml/g blood at arterial hematocrit 37% and 0.42 ml/g blood at hematocrit 75%, perfused by 0.9 and 0.1 of the arterial inflow respectively. Evidence suggests these spaces are i) blood vessels, and ii) red pulp.

pH environmental of red cells in the spleen

Levesque, Groom — 1976-12-01

Intrasplenic pH in vivo was deduced from measurements on blood drained from cat spleen during contraction with the inflow occluded. The pH of blood in the red pulp is normally 7.20, but stasis or reduced flow through the pulp causes pH to fall toward 6.8. The splenic pulp contains blood of high hematocrit. To evaluate the role of buffering by the red cells themselves, intrasplenic p/ in red cell-free spleens was, therefore, estimated atering and leaving the spleen during red cell washout. At inflow pH less than 6.8 the outflow pH was raised, at inflow pH = 6.8 there was no change, b,t at inflow pH greater than 6.8 the outflow pH was lowered. These results indicate that the pH environment of red cells in the spleen results indicate that the pH environment of red cells in the spleen results from the interplay of two separate factors: i) pH-determining elements of the splenic tissue that buffer at 6.8, and ii) buffering provided by red cells passing through the pulp.

Relationships between resting tension and mechanical properties of papillary muscle

Templeton, Adcock, Willerson, Nardizzi, Wildenthal, Mitchell — 1976-12-01

The influence on mechanical properties of changes in resting tension over a range from 0.5 to 4.5 g was investigated in 12 isolated cat papillary muscles. At each resting tension, the muscles contracted isometrically with the exception of an externally applied sinusoidal stretch of 0.5% Lmax (deltaL) and 20 Hz. Stiffness (deltaT/deltaL) was determined from deltaL and the peak amplitudes (deltaT) of the individual cycles from the sinusoidal component of tension. Assuming that the muscle and experimental apparatus behaved as a linear second-order mechanical system, it was possible to divide stiffness into its elastic and viscous components. During rest, total stiffness and its components were linearly related to tension. During contraction, stiffness and its elastic component were linearly related to tension. Furthermore, increasing resting tension increased the intercept and decreased the slope of this linear stiffness-tension relationship. The relationship between viscous stiffness and tension during contraction is more complex in that it is a direct relationship at low resting tensions, but an inverse one at high resting tensions.

Contributions of pressure and flow sensitivity to autoregulation in mesenteric arterioles

Johnson, Intaglietta — 1976-12-01

The relative influence of presence and flow on dilation of arterioles with pressure reduction was examined in preparations of cat mesentery. Erythrocyte velocity and diameter were measured in individual arterioles during stepwise reduction in mesenteric arterial pressure. Volume flow was calculated from velocity and diameter data. Approximately half of the arterioles which dilated with pressure reduction also showed an increase in volume flow. In a second series of experiments, a graded reduction of flow in single arterioles was produced by local downstream occlusion. Graded occlusion caused dilation. In a third series, flow in single arterioles was completely stopped by downstream occlusion, and arterial pressure was then lowered. Most arterioles dilated with pressure reduction. In a fourth series, flow in the total preparation was completely stopped and static intravascular pressure set by a reservoir. Elevation of static pressure typically produced arteriolar constriction. We conclude from these studies that the mesenteric arteriole is sensitive both to intravascular pressure and flow, with the former probably more important than the latter in the phenomenon of autoregulation.

Nephron function of the isolated perfused rat kidney

De Mello, Maack — 1976-12-01

Nephron functions of an improved isolated perfused rat kidney preparation were studied by micropuncture techniques. Single-nephron glomerular filtration rate (SNGFR), intratubular pydrostatic pressures (IP), transit time (TT), and the reabsorption (R) of H2O, Na, Cl, and K were measured in superficial proximal (PT) and distal tubules (DT) of the preparation. Mean SNGFR was 27.2 nl/min and 25.2 nl/min when measured in PT and DT, respectively. The PT transport functions were well maintained throughout the perfusion (mean values were: IP, 14.3 mmHg; TT, 17.7 s; fractional (F) RH2O, 64%; absolute RH2O, 15.4 nl/min; FRNA, 66.5%; FRK, 71%, and tubular fluid-to-perfusate tf/p) ratio of Cl, 1.37). The short loops of Henle reabsorbed less than 10% of the load of H2O and Na delivered to them and the TF/P ratio of electrolytes in the earliest DT segments were high (TF/P)Na = 0.88, (TF/P)Cl = 1.27, and (TF/P)K = 1.11). This deficiency in function of Henle's loop explains, at least in part, the degree of natriuresis of the preparation (overall FRNa = 97.5%). Transit time to end DT was prolonged (82.3 S) and IP in DT elevated (14.9 mmHg). The DT was able to compensate, in part, for the overload from Henle's loop by reabsorbing 36% of the fluid load and 54% of the Na load delivery to it. We concluded that the improved isolated perfused rat kidney is a suitable preparation with which to study several aspects of renal function, particularly proximal tubules transport functions.

Sustained pressore responsiveness to prolonged hypothalamic stimulation in awake rats

Bunag, Riley, Montello — 1976-12-01

Whether or not pressor responsiveness changes in unanesthetized rats during recurrent sympathetic excitation was determined by recording blood pressure and heart rate continuously while the posterior hypothalamus was stimulated repeatedly with constant currents. Because preliminary tests showed that telestimulation with a radio-controlled stimulator produced erratic responses, awake rats were routinely stimulated in a conventional manner by connecting them through wires to a square-wave stimulator. Although tachycardia was the most common chronotropic effect, bradycardia also occurred, and both responses were occasionally seen in the same rat at different times. Inhibition of chronotropic responses by combined pharmacologic blockage with propranolol and atropine did not affect corresponding pressure responses in normotensive rats. Renal and spontaneously hypertensive rats always had larger pressor responses than normotensive ones, and, in spite of individual variations, responsiveness generally remained unaltered during 3-6 h of repeated hypothalamic stimulation. These results indicate that in awake normotensive or hypertensive rats cardiovascular responses to posterior hypothalamic stimulation continue unabated even when stimulation is repeated for hours.

Glucose transport in isolated perfused proximal tubules of snake kidney

Barfuss, Dantzler — 1976-12-01

Glucose transport was studied in isolated, perfused snake (Thamnophis spp.) renal tubules. When 14C-labeled and unlabeled glucose concentrations for bath and perfusate were identical, net transepithelial glucose transport occurred from lumen to bath. Maximum rates of transport were 1.24 X 10-12 and 2.17 X 10-12 mol min-1 mm-1 in proximal-proximal and distal-proximal segments, respecitvely. Glucose concentration in cells of perfused tubules of both segments was less than that of bath and lumen when tubules spontaneously stopped transporting glucose. Transepithelial glucose permeability ath leads to lumen) was about 0.25 X 10-5 cm sec-1 for both segments. Peritubular membrane permeability (bath leads to cell) was about 0.50 X 10-5 cm sec-1 for both segments. Luminal membrane permeabilities (cell leads to lumen) were 0.29 X 10-5 and 0.65 X 10-5 cm sec-1 for proximal-proximal and distal-proximal segments, respectively. Luminal membrane permeability in opposite direction (lumen leads to cell) was about 10.0 X 10-5 cm sec-1 for both segments. These results indicate that, during maximum glucose absorption, glucose enters cells down concentration gradient across luminal membrane by a mediated process and is transported out of the cells against concentration gradient at peritubular membrane.

A role for glucose in hypothermic hamsters

Resch, Musacchia — 1976-12-01

Hamsters undergo hypothermia when exposed to a mixture of 80% helium and 20% oxygen at low ambient temperatures. The hypothermic hamster, rectal temperature (Tre) 7 degrees C, becomes hypoglycemic, and reversal of hypoglycemia is effected with glucose infusion. Hypothermic hamsters at Tre 7 degrees C showed a fivefold increase in survival times from 20 to 100.5 h when infused with glucose which maintained a blood level at about 45 mg/100 ml. A potential role for osmotic effects of the infusion was tested and eliminated. There was no improvement in survival of 3-O-methylglucose or dextran 40-infused animals. The fact that death eventually occurs even in the glucose-infused animal after about 4 days and that VO2 undergoes a slow decrement in that period suggests that hypothermic survival is not wholly substrate limited. Radioactive tracer, [U-14C]glucose, showed that localization of the 14C, was greatest in brain tissue and diaphragm, intermediate in heart and kidney, and lowest in skeletal muscle and liver. The significance of the label at sites important to respiration and circulation was presented.

Na-K-ATPase localization in teleost urinary bladder by [3H]ouabain autoradiography

Renfro, Miller, Karnaky KJ, Kinter — 1976-12-01

Previous studies on the urinary bladder of the seawater-acclimated winter flounder (pseudopleuronectes americanus) demonstrated that active Na and Cl transport were ouabain sensitive. This suggested a relationship between the Na pump and Na-K-ATP-ase. The specific binding of [H]ouabain to Na-K-ATPase provides a means of localizing the site of active Na transport. In isolated bladders, a positive linear correlation (r= 0.89) was found between the active Na transport rate and the Na-K-ATPase activity. Ouabain binding by the bladder surface appeared to be saturable and relatively specific, e.g., was reduced by a high K concentration. When only the mucosal side of the bladder was exposed to 5 muM ouabain, both inhibitory effects and binding were small and are explained by finite permeability of the bladder to ouabain. In contrast, binding and inhibitory effects from the serosal side were much greater. Autoradiographs demonstrated that [3H]ouabain was bound only to the serosal side of the epithelial cells. Ultrastructural examination revealed that the area of ouabain binding coincided with the basal and lateral plasma membranes.

Tubuloglomerular feedback: effect of dietary NaCl intake

Kaufman, Hamburger, Flamenbaum — 1976-12-01

Response to angiotensins I and II and to AI-converting-enzyme inhibitor in a shark

Opdyke, Holcombe — 1976-12-01

The spiny dogfish shark, which does not have renal juxtaglomerular cells, exhibits a strong pressor response to both angiotensin I and II. A nonapeptide, angiotensin I-converting-enzyme inhibitor, blocks the pressor response to angiotensin I in this fish. The pressor response to both angiotensin II and norepinephrine is completely blocked by the adrenergic blocking drug phentolamine.

Lithium-induced diuretic effect of antidiuretic hormone in rats

Dousa, Barnes — 1976-12-01

The effect of a low dose of lithium (1 meq/kg per day) on renal function and its response to antidiuretic hormone (ADH) was studied in unanesthetized rats. This dose of lithium itself had no influence on renal water and electrolyte excretion, but lithium-treated rats responded paradoxically to exogenous ADH by increases in urinary volume, excretion of total solutes, sodium, potassium, and phosphate. Administration of ADH in the presence of lithium led to a lowering of urine osmolality, but free water clearance was not significantly reduced. Adenylate cyclase from the renal medulla of animals treated with ADH and lithium had a lower response to synthetic vasopressin in vitro than in animals treated with lithium alone. The results suggest that exogenous ADHis diuretic in the presence of a low concentration of lithilm. The predominant mechanism for this diuresis is probably inhibition of electrolyte and isomotic water reabbsorption in various nephron segments, including those proximal to the collecting ducts. ADH also markedly increased urinary excretion of lithium and appears to promote accumulation of lithium in the renal medulla.

Effect of graded doses of cortisol on total body calcium in rats

Yasumura, Ellis, Fairchild, Brook, Cohn — 1976-12-01

Male rats with an average body weight of 250 g were injected (sc) daily for 4 wk with 0.05, 0.20, 0.75, or 3.00 mg of cortisol acetate. Intact and adrenalectomized control animals were injected daily with 0.1 ml of vehicle (corn oil). Total body calcium (TBCa) was measured weekly in each rat by in vivo neutron activation analysis. The gain is body weight of rats treated with 0.75 mg cortisol was significantly less than controls, and the animals treated with 3.00 mg cortisol lost weight. In spite of these differences in body weight, the TBCa of all rats increased to an equal degree from an average of 1.93 g to 2.81 g in 4 wk. In addition, there were no significant differences in tibial ash calcium. However, calcium (mg) per unit length (mm) of tibia was increased in rats treated with the higher doses of cortisol; thus bone density was increased. These results demonstrate that the TBCa increases even when rats are subjected to cortisol. This is explained in part by the normal rate of intestinal calcium absorption in cortisol-treated rats.

Acid-base regulation in pregnancy

Lim, Katz, Lindheimer — 1976-12-01

Plasma bicarbonate decreases during normal pregnancy. To assess what roles increased extra cellular volume or alterations in parathyroid hormone levels (iPTH) have in the maintenance of this decrement, we evaluated acid-base metabolism in eleven 3rd-trimester women. Base-line pH and PCO2 were 7.44 and 27.3 mmHg, respectively. Mean tubular reabsorption of phosphate was 93% and baseline iPTH levels were similar to those of nonpregnant subjects. During the slow infusion of hypertonic NaHCO3, a urinary threshold of HCO3- (THCO3) appeared at a mean plasma level of 18.9 meq/liter, but as plasma HCO3- increased progressively, its renal reclamation was almost complete and there was no evidence of either splay or tubular maximum, even when filtered loads of HCO3- reached 5 meq/min. Urine acidification was normal and distal [H+] secretory ability( deltaidification was normal and distal [H+] secretory ability (delta urinary PCO2) was similar to that reported in nongravid subjects. In metabolic balance studies blood pH and plasma HCO3- increased (P less than .01 and less than .02, respectively) when the women changed from a high- to a low-sodium diet. Mechanisms by which decreased plasma bicarbonate levels are maintained during gestation are discussed.

Effect of hypermagnesemia on rat jejunal sodium and water transport

DiBona, Sawin — 1976-12-01

Hypermagnesemia decreases sodium and water reabsorption in the rat renal proximal tubule. To further understand this action, the effect of hypermagnesemia on sodium and water transport in the in vivo perfused rat jejunum was studied. The rat jejunum was chosen as another transporting epithelial tissue in the same species with unidirectional sodium flux characteristics similar to the rat renal proximal tubule, i.e., leaky as opposed to tight. Hypermagnesemia decreased net jejunal sodium and water reabsorption. This decrease was due to a reduction in unidirectional sodium efflux from lumen to blood and not to an increase in unidirectional sodium influx from blood to lumen. Hypermagnesemia did not change the jejunal permeability to inulin. The effect of hypermagnesemia on jejunal sodium and water transport is similar to that renal proximal tubule sodium and water transport. This similarity suggests that the mechanism of action of magnesium of these two transporting epithelial tissues is similar.

Hemodynamic pulmonary edema in dogs with acute and chronic lymphatic ligation

Magno, Szidon — 1976-12-01

The effect of lymphatic ligation on relative lung water (g H2O/g dry lung) was studied in dogs. Raising left atrial pressure to 20 mmHg for 2 h in chronically lymphatic-ligated dogs (4 days) caused a significantly greater increase in relative lung water than the same hemodynamic challenge did in sham-operated and acutely lymphatic-ligated dogs. There was no significant difference in relative lung water between the acutely lymphatic-ligated and sham-operated dogs. At normal left atrial pressures, there was no significant difference in relative lung water between the sham-operated and chronically lymphatic-ligated dogs. Since the combined effects of chronic lymphatic ligation and left atrial hypertension is greater than the sum of the individual effects, it appears that chronic lymphatic ligation increases the susceptibility of the lung to hemodynamic edema, we suggest that chronic lymphatic ligation may have produced increases in the interstitial volume and protein mass that are undetectable by our technique. These increases, in turn, could lead to a reduction in tissue safety factors against hemodynamic pulmonary edema.

Ion transport across isolated antral mucosa of the rabbit

Fromm, Schwartz — 1976-12-01

Isotopic fluxes of Na, Cl, and K were measured across isolated antral mucosa under short-circuit conditions. HCO3 fluxes were also measured with either isotopic and/or pH-stat methods. Net secretion of all four ions was observed. HCO3 secretion is due to a transmural process requiring metabolic energy. Secretion of endogenous HCO3 was not observed, and the unidirectional mucosal-to-serosal flux of HCO3 was negligible. There appears to be a close relationship between HCO3 secretion and the unidirectional mucosal-to-serosal Cl flux, but not relationships were observed between the unidirectional serosal-to-mucosal flux or either unidirectional Na flux. The bulk of HCO3 secretion is independent of the unidirectional Cl fluxes, but there is a fraction of HCO3 transport that is dependent on unidirectional Cl transport. However, HCO3 transport is not measurably influenced by inhibition of net Cl (and Na) transport per se.

Dietary self-selection following subdiaphragmatic vagotomy in the white rat

Fox, Kipp, VanderWeele — 1976-12-01

Nineteen female Wistar rats were employed in a self-selection-of-diet study assessing the effects of vagotomy on macronutrient consumption. Nutrients offered were a 30% sucrose solution, a 15% casein hydrolysate solution, and olive oil. In addition, noncaloric bulk, vitamins, and water were allowed. Bilaterally, subdiaphragmatically vagotomized rats showed a significant decrement in carbohydrate ingestion and daily total caloric intake (P less than .05 in both comparisons). Fat and protein intakes were unreliably altered. It is hypothesized that the vagus nerve relays glucose absorption and/or storage information from the periphery to the brain (perhaps lateral hypothalamusy, and hence, vagotomy produces carbohydrate-intake decrements, specifically. The decrement could also be explained as resulting from efferent effects of vagotomy such as decreased gut hormonal release.

Central antihypertensive effects of inhibitors of the renin-angiotensin system in rats

Sweet, Columbo, Gaul — 1976-12-01

The possibility that mean arterial pressure (MA) might be maintained by an effect of angiotensin II or its precursors on the central nervous system in rats made hypertensive by occluding the aorta between the renal arteries was investigated. Aortic coarctation produced severe hypertension (MAP greater than 150 mmHg) and plasma renin activity values (radioimmunoassay) at least 10 times normal within 2-6 days after surgery. [Sar1, IIe8]angiotensin II, an angiotensin II antagonist administered centrally via an intracerebroventricular (icv) injection (10-100 mug), lowered the MAP in a dose-dependent manner. Peripheral administration of [Sar1, IIe8]angiotensin II (bolus injection) at 100 mug intra-arterially was ineffective, but the antagonist did lower arterial pressure when infused intravenously for 1 h at 4 times this dose. Less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, a converting enzyme inhibitor, and pepstatin, a renin inhibitor, were ineffective via an icv injection. These results suggest that angiotensin II is in part responsible for the elevation in blood pressure following aortic coarctation in rats. Both central and peripheral administration of [Sar1, Ile8]-angiotensin II lowered mean arterial pressure but the antagonist lowered arterial pressure at lower doses and produced a more rapid decline in arterial pressure when administered into the central nervous system then when administered intra-arterially or intravenously.

Influence of oxygen and glucose on the water and ion content of swine aorta

Harrrison, Massaro — 1976-12-01

The swelling properties of isolated swine arterial tissue have been studied to determine their effect on diffusion and hydraulic permeability measurements. Tissue potassium and sodium content were also measured to obtain an index of tissue metabolic activity. When oxygen and glucose were present in the incubation medium, a 5% decrease in tissue water content was observed over an incubation period of approximately 3.5 h. Under these conditions the tissue potassium content was higher and the sodium content was lower than when oxygen and/or glucose were omitted from the medium. When both oxygen and glucose were omitted, the potassium and sodium levels were significantly altered, suggesting a disturbance in the sodium-potassium transport system due to depletion of necessary metabolities.

Extracellular space of swine aorta measured with [14C]inulin and [14C]sucrose

Harrison, Massaro — 1976-12-01

Measurements of the extracellular space (ECS) of the isolated swine thoracic aorta were performed with both [14C]inulin and transient measurements and appeared to have better access to available tissue water than the [14C]sucrose gave more consistent results in available tissue water than the [14C]inulin. With [14C]sucrose as the tracer, no significant difference in the ECS was found when the tissue was incubated for 1.5 h in the presence of oxygen and glucose as compared to an incubation in which both oxygen and glucose were absent. However, the ion contents were markedly altered by this change in incubation medium. When oxygen and glucose were present tissue K+ was significantly higher and tissue Na+ was significantly lower than when these metabolites were deleted from the medium. Thus, significant alteration in ion content did not lead to substantial cell damage or bursting.

In vivo control of mitochondrial enzyme concentrations and activity by oxygen

Mela, Goodwin, Miller — 1976-12-01

Newborn and adult dog heart mitochondria were prepared from animals chronically adjusted to varying arterial oxygen tensions. Similarly, rat liver and heart mitochondria were isolated from animals acutely exposed to lowered inspired oxygen. After isolation, all mitochondrial samples were assayed under normoxic conditions. These experiments illustrated the following effects of oxygen on mitochondrial function: 1) respiratory activity in State 3 or in the uncoupled state increased after hypoxia and decreased after increased in vivo oxygenation; 2) similarly, the turnover of cytochrome oxidase increased in hypoxia and decreased after increased oxygenation; 3) after chronic hypoxia cytochrome oxidase, cytochrome c and b concentrations decreased per miligram of mitochondrial protein; 4) all mitochondrial preparations were well coupled and exhibited normal capabilities to perform oxidative phosphorylation. The data are interpreted to indicate sensitive control of mitochondrial respiratory capacities by oxygen in vivo.

Characterization of leucine transport by toadfish liver in vivo

Persell, Haschemeyer — 1976-12-01

Kinetic analysis of L-leucine uptake by toadfish liver at 20 degrees C in vivo has been carried out after pulse injection of L-[14C]leucine into the hepatic portal vein. D-[3H]mannitol, which is taken up slowly by toadfish liver, is used as a marker for extracellular space and space accessible by simple diffusion. At normal plasma leucine concentration (0.1 mM), leucine uptake occurs rapidly (t1/2 = 0.25 min), representing a flux of 0.6 mumol/min for the liver as a whole. Analysis of the distribution of radioactive leucine among intracellular and extracellular free pools and protein-bound form at times of 30 s to 5 min after injection is consistent with operation of a concentrative or uphill transport system accounting for 40% of uptake at normal plasma concentration. Saturation of uptake occurs at increasing leucine loads; calculation of intracellular pool dilution from protein synthesis data indicates that 20-30% of liver intracellular space is occupied by incoming leucine during the first 2 min after portal injection. Maximal flux (V max) is 4.1 mumol/min per 7-g liver as a whole with Km = 0.6 mM. Competitive inhibition of leucine uptake is afforded by isoleucine and phenylalanine with lesser effects by aspartic acid, cysteine, methionine, threonine, tyrosine, and valine. No effect is observed with alanine, glycine, histidine, lysine, and proline.

Mechanism of pellet egestion in great-horned owls (Bubo virginianus)

Duke, Evanson, Redig, Rhoades — 1976-12-01

To study the mechanism of oral pellet egestion in great-horned owls, bipolar electrodes and strain-gauge transducers were chronically implanted in the esophagus, muscular stomach, and duodenum of six owls. Recordings from conscious owls plus simultaneous radiographic observations revealed characteristic gastrointestinal motility patterns associated with egestion. Beginning at about 12 min before egestion, gastric contractions formed the final shape of the pellet and pushed it into the lower esophagus. The pellet was moved out of the esophagus by antiperistalsis during the last 8--10 s before egestion. During pellet egestion, contractions of abdominal muscles were not detected. Pellet egestion appears to be unlike either emesis in mammals with a simple stomach or regurgitation in ruminants.

Regulation of avian insulin secretion by isolated perfused chicken pancreas

King, Hazelwood — 1976-12-01

Chicken insulin secretory responses to glucose, glucagon, tolbutamide, and lack of Mg2+ were measured using isolated perfused in situ chicken pancreata. Although elevating perfusate glucose concentration from 100 to 250 mg/100 ml failed to increase insulin release, 500 mg glucose/100 ml provoked a transient 5-min insulin response. Additionally, 700 mg glucose/100 ml resulted in both a transient response and subsequent elevation in secretory rate that continued throughout the following 50-min stimulatory period. Glucagon (500 microgram/ml) and omission of perfusate Mg2+ potentiated glucose-stimulated insulin output by 6 and 25%, respectively. A faster release of insulin (less than 1 min) occurred during tolbutamide infusion (0.13 mg/ml) than with either 500 or 700 mg glucose per 100 ml (2-3 min); however, secretory rates declined to near basal levels within 5 min. Mammalian-like insulin responses to glucose, glucagon, Mg2+ lack, and tolbutamide suggest similarities between avian and mammalian beta-cell insulin secretory mechanisms. Nevertheless, the relatively high chicken insulin release threshold and low insulin output to glucose indicate that chicken pancreata are relatively glucose insensitive.

Relationship of cerebral oxygen uptake to EEG frequency in isolated canine brain

Fitzpatrick, Gilboe, Drewes, Betz — 1976-12-01

Cerebral oxygen uptake was correlated with electroencephalographic (EEG) frequency and amplitude in 87 isolated canine brains. Group I (71 brains) was perfused with diluted blood and Group II (16 brains) was perfused with whole blood equilibrated with oxygen at various partial pressures. The EEG's were classified as follows: A, highest frequency greater than or equal to 17 Hz, alpha (8-13 Hz) amplitude less than 50 muv, delta (less than or equal to 3.5 Hz), amplitude less than 100 muv; B, highest frequency greater than or equal to 17 Hz, alpha amplitude greater to or equal to 50 muv, and/or delta amplitude greater than or equal to 100 muv. C, highest frequency 8-16 Hz, alpha amplitude greater than or equal to 25 muv, and delta amplitude greater than 100 muv, D, highest frequency 0.5-16 Hz, alpha, if present, amplitude less than 25 muv, and/or delta amplitude less than 100 muv, and E, highest frequency 0-16 Hz, alpha, if present, amplitude less than 10 muv, and/or delta amplitude less than 15 muv. The Group I oxygen uptakes in ml/100 g of brain per min+/-SE for the five EEG classifications were A, 4.39+/-0.06, B, 4.13+/-0.08, C, 3.76+/-0.09, D, 3.40+/-0.12, and E, 2.55+/-0.06, whereas the corresponding Group II values were A, 4.64+/-0.22, B, 4.28+/-0.15, C, 3.82+/-0.24, D, 3.39+/-0.40, and E, 1.38+/-0.42. As the EEG deteriorates, cerebral oxygen uptake tends to decrease in a significant and parallel manner in both the diluted and whole blood groups.

Independent secretion of different digestive enzymes by the pancreas

Rothman — 1976-12-01

Pancreatic secretion was collected from the cannulated duct of anesthetized rabbits during the perfusion of the upper duodenum with a balanced salt solution with or without 5 mM glucose. The secretion of amylase, chymotrypsinogen, trypsinogen, and total protein was measured. While glucose did not increase overall digestive enzyme secretion, it did change the proportions of the enzymes in secretion. In addition, the following was observed: 1) non-0,0 intercepts when the output of one enzyme was plotted against that of another (an enzyme-pair plot), 2) changes in the variance of the slope and intercept of enzyme-pair plots, and 3) an increase in the variance around the slope of an enzyme-pair plot, concurrent with a decrease in the variance around the slope of a plot for another enzyme pair that contained a common member. These observations suggest that different digestive enzymes can be secreted independently of each other.

Coronary intercapillary distance during growth: relation to PtO2 and aerobic capacity

Henquell, Odoroff, Honig — 1976-12-01

Intercapillary distance (ICD) was measured in left ventricles of rats beating in situ. Between 40 and 400 days of age, left ventricular weight increased threefold and ICD increased from 12.5-19.5 mum. ICD could be decreased by at least 2 mum at all ages studied. The number of capillaries which must be recruited to reduce ICD by 2 mum fell from 1,200/mm2 at 40 days to 280/mm2 at 400 days. Ventricular growth did not affect the O2 sensitivity of precapillary sphincters or the uniformity of capillary spacing. Calculations indicate that under basal conditions tissue PO2 (Pto2) in subepicardium is about the same at 40 and 400 days, even though VO2 per gram, capillary density, and ICD change twofold, twofold, and 7 mum, respectively. Nevertheless, as the ventricle grows, capillary recruitment becomes progressively less effective in defending Pto2 under conditions of stress. Diminished coronary capillary compensation for stress may, in part, account for the effect of age on the maximum aerobic capacity of the whole animal.

Parallel secretion of digestive enzymes by the in vitro rabbit pancreas

Steer, Glazer — 1976-12-01

Nonparallel discharge of digestive enzymes by the in vitro rabbit pancreas has been previously reported and this observation has been used to challenge the mass transport theory of enzyme synthesis and secretion by the exocrine pancreas. The current investigation reexamines the pattern of enzyme secretion from the in vitro rabbit pancreas. Secretion of alpha-amylase, trypsinogen, and chymotrypsinogen was studied from the unstimulated gland and from glands stimulated with either methacholine, cholecystokinin-pancreozymin, or the active octapeptide of cholecystokinin-pancreozymin. In all cases, only parallel discharge of alpha-amlyse, trypsinogen, and chymotrypsinogen was noted. These observations are consistent with the mass-transport theory.

Transepithelial transport kinetics and Na entry in frog skin: effects of novobiocin

Cruz, Biber — 1976-12-01

Na+ entry across the outer surface of frog skin and transepithelial Na transport were studied simultaneously at different [Na] in either the presence or absence of novobiocin by direct measurements of J12 (unidirectional uptake) and Io (short-circuit current). J12 consisted of two components: one linear, the other saturable. The kinetic parameters of the saturating components in controls were close to the kinetic parameters of overall transepithelial transport (Jm12 = 1.68+/-0.13 mleq cm-2h-1; Io =1.80+/-0.14 mueq cm-2h-1. K12 = 6.02+/-1.27 mM;Kio=6.12+/-1.33 mM). Novobiocin significantly augmented net transepithelial Na transport by increasing J13. J31 remained unaffected. A 1:1 relationship between the saturating component of J12 and Io was observed in both treated and untreated skins at all [Na] tested. (Jm12Iom, k12, and Kio were significantly larger in treated skins, but despite very drastic changes in transport rates, a close correlation between kinetic parameters of entry step and transepithelial transport was maintained. This suggests that the kinetics of transepithelial transport may simply reflect those of the rate-limiting step: the Na entry across the outer barrier of the skin. The results indicate that the linear component of J12 is not involved in transepithelial transport kinetics.

Effect of glycodihydrofuisidate on sulfobromophthalein transport maximum in the hamster

Delage, Dumont, Erlinger — 1976-12-01

The effect on sulfobromophathalein transport maximum (Tm) and biliary lipid secretion of sodium glyco-24,25-dihydrofusicate, a micelle-forming compound secreted into bile, has been studied in the hamster and compared to that of a physiological bile salt, sodium taurocholate. Biliary phospholipid and cholesterol secretion increased both during glycodihydrofusidate and taurocholate administration, an observation which suggest that both compounds increased th biliary secretion of micelle-forming compounds. In contrast, only taurocholate increased sulfobromophthalein Tm into bile, while glycodihydrofusidate administration decreased it. This observation suggests that the increase in sulfobromophthalein Tm observed during taurocholate administration is not the result of micellar sequestration. It could rather be the consequence of a specific effect of bile salts on the dye transport system.

Permeability of erythrocyte membranes

Hunter — 1976-12-01

Estimation of ENa from current-voltage curve

Li — 1976-12-01