bluuebunny/crossref_metadata_2025 huggingface dataset:
Primate kidney function in hemorrhagic shock as influenced by dibutyryl cyclic AMP
Authors: Selkurt EE
Published: December 2017

Standardized hemorrhagic shock was employed to study alterations in electrolyte and water handling in the owl monkey, either normally hydrated or moderately dehydrated. Increase in fractional clearance of osmolarity,sodium, and calcium occurred with retransfusion after the hypotensive phase. In the hydrated animals, free-water clearance became positive, and the urine-to-plasma osmolarity ratio [(U/P)osM] decreased below 1.0. In the dehydrated animals, free-water reabsorption (TCH2O) decreased but remained negative,while (U/P)osM remained above 1.0. Dibutyryl cyclic AMP (DBcAMP) was infused into the renal arterial supply in an attempt to correct a possible deficiency of cyclic AMP production. In the hydrated group, free-water clearance (CH2O) became more positive with infusion, and (U/P)osM decreased even further, with no effect on fractional sodium clearance. Effects were less or absent in the dehydrated group. Possible explanations for the observed effects of DBcAMP are considered. It was concluded that the loss of concentrating power seen in hemorrhagic shock occurs at a step beyond the production of cyclic AMP by adenylate cyclase.
Potassium flux in smooth muscle of frog stomach
Authors: Stephenson EW
Published: December 2017

In frog stomach muscle fibers, normal steady-state K flux, estimated directly from 42K uptake, was 0.17 pmol/cm2 per s at 5 degrees C and 0.63 pmol/cm2 per s at 15 degrees C. Influx characteristics were studied at 5 degrees C, where backflux and diffusional delay effects are minimized. Steady-state K influx was a saturating function of external [K] over the range 0.25-11 mM [K]o; influx at normal and higher [K]o did not differ significantly. Na loading (in K-free or low K solution) strongly stimulated influx, which showed altered saturation kinetics; maximal K influx was a quasilinear function of internal [Na]. Ouabain (10(-4) M) reduced normal and stimulated K influx markedly. Ethacrynic acid (10(-3) M) caused net K loss and Na gain, but increased K influx fourfold; ouabain inhibited the stimulated influx by 50%. These results indicate that K influx depends mainly on cycling of the Na-K pump and is normally limited by Na efflux. Ethacrynic acid may stimulate another mode of pump operation, K-K exchange, and uncouple the normal operation.
Renal excretion of uric acid in the rat: a micropuncture and microperfusion study
Authors: Roch-Ramel F , Diezi-Chomety F , De Rougemont D , Tellier M , Widmer J , Peters G
Published: December 2017

Free-flow micropuncture experiments were done in rats of three strains infused with small amounts of urate [plasma urate (P urate) = 95 +/- 8 muM]. Urate concentrations in tubular fluid were measured by an accurate chemical fluorometric ultramicromethod. In fluid from surface glomeruli, the glomerular fluid-to-plasma urate ratio [GF/P) urate] was 0.99 +/- 0.03 (n=11), i.e., lower than expected for total ultrafiltrability of plasma urate. Along proximal convolutions, net reabsorption of 55% of filtered urate was demonstrated. Small amounts of urate may have been reabsorbed between late proximal and early distal sites. Net transepithelial movements of urate did not occur in distal tubules or collecting ducts. In microperfusion experiments on proximal tubules, both a reabsorptive flow of urate (loss of perfused [2-14C]urate) and a secretory flow (entrance of cold urate into perfusate) of the same order of magnitude were demonstrated. Neither flow was influenced by simultaneous water movements. Microperfusion of Henle's loops indicated a significant but very small net reabsorption.
Increase in renin release after sionaortic denervation and cervical vagotomy
Authors: Yun JC , Delea CS , Bartter FC , Kelly G
Published: December 2017

The role of the vagi in the control of renin secretion was investigated in dogs maintained on a high-salt diet. Renal perfusion pressure was maintained relatively constant by the manipulation of a suprarenal aortic snare. Mean arterial blood pressure (MAP), plasma renin activity (PRA), and packed cell volume (PCV) increased after sinoaortic denervation and cervical vagotomy. Cooling of cervical vagi to 3-5 degrees C had the same effect as vagotomy. There was no change in MAP, PRA, and PCV in sham-operated animals. Propranolol prevented the increase in PRA following sinoaortic denervation and vagotomy, but not that in MAP or PCV. In splenectomized dogs, PCV still showed increases after sinoaortic denervation and vagotomy. It is suggested that the removal of sinoaortic and/or vagal inhibitory effects on the vasomotor center causes increases in sympathetic discharge to the adrenal medulla and the peripheral vessels, and that this in turn leads to the increase in MAP. The increase in sympathetic discharge to the adrenal medulla and the kidney causes the increases in PRA.
Intrarenal calcium in phosphate handling
Authors: Cuche JL , Ott CE , Marchand GR , Diaz-Buxo JA , Knox FG
Published: December 2017

The intrarenal role of plasma ionized calcium (Ca), on fractional phosphate excretion (FE PO4) was investigated in dogs with control of parathyroid hormone (PTH). In series 1, acute thyroparathyroidectomy was immediately followed by a constant infusion of bovine PTH (0.01 U/kg per min). Subsequent calcium chloride infusions increased Cai in plasma phosphate and decreased in the percentage of ultrafiltrable phosphate. A 20% increase in Cai significantly increased FE PO4 by +3.82 +/- 0.97% (P less than 0.01) when infused intravenously and by +2.62 +/- 1.06% (P less than 0.05) when infused in the renal artery. In contrast, a 75% increase in Cai did not significantly change FE PO4. In series 2, dogs were thyroparathyroidectomized 18 h before experiments, and no PTH infusion was initiated. A bolus of bovine PTH (30 U/kg) increased FE PO4 + 8.9 +/- 0.9% (P less than 0.001) in hypocalcemic dogs, +19.1 +/- 4.4% (P less than 0.001) in normolcalcemic dogs, and +15.5 +/- 1.5% (P less than 0.001) in hypercalcemic dogs. We conclude that increases in plasma calcium potentiate the phosphaturic effect of PTH. This potentiating effect is attenuated in marked hypercalcemia by superimposed hemodynamic and/or metabolic changes.
Intracellular pH of brain: alterations in acute respiratory acidosis and alkalosis
Authors: Arieff AI , Kerian A , Massry SG , DeLima J
Published: December 2017

To evaluate the metabolic adaptations of the brain to acute respiratory acid-base disturbances, a method was developed to measure intracellular pH (pHi) in the brain of dogs under conditions in which arterial pH is rapidly altered. Brain pHi was determined by measuring the distribution of 14C-labeled dimethadione (DMO) in brain relative to cortical CSF. Brain extracellular space (ECS) was evaluated as the 35SO4 = space relative to cortical CSF, and arterial Po2 was maintained at 82-110 mmHg. In normal dogs, brain (cerebral cortex) pHi was 7.05, and after 1 h of hypercapnia (arterial pH = 7.07) it fell to 6.93. However, after 3 h with arterial Pco2 maintained at 85 mmHg brain pHi was normal (7.06), and during this time brain bicarbonate had risen from 11.3 to 24.4 meq/kg H2O. These changes were not prevented by intravenous doses of acetazolamide,
Feeding behavior in monkeys with and without lesions of the hypothalamus
Authors: Hamilton CL , Ciaccia PJ , Lewis DO
Published: December 2017

In monkeys (Macaca mulatta) without hypothalamic lesions, food intake was found to increase with increasing age and body weight; however, food intake per kilogram body weight showed a decline over the same period of time. As the animals became older, the amount of food intake converted to body weight decreased dramatically (feeding efficiency). Water intake was shown to be closely coupled to food intake. Both daily food and water-intake data were highly reliable over a period of years. Monkeys with ventromedial hypothalamic lesions exhibited hyperphagia and increased feeding-efficiency ratios and eventual obesity. The obese animals developed symptoms of diabetes mellitus. Animals with lesions restricted primarily to the arcuate nucleus showed no hyperphagia but increased feeding efficiency. These animals exhibited decreased growth hormone release and a transitory elevation of serum insulin.
Inhibition of the CNA trigger process for arousal from hibernation
Authors: Beckman AL , Stanton TL , Satinoff E
Published: December 2017

Ground squirrels (Citellus lateralis) produced three distinct types of thermogenic response during hibernation. These responses were evoked spontaneously as well as after stimulation produced by brief handling, or after microinjection of acetylcholine into the midbrain reticular formation. Type I responses were characterized by small magnitude and a slow (mean rate, 0.03 degrees C/min), variable rising phase. Type II responses were characterized by a smooth, rapid rising phase with a mean rate of increase of 0.11 degrees C/min and by an abrupt reversal of the rising phase within a restricted ceiling temperature band with a mean value of 9.4 degrees C. The third type of response, full arousal, was characterized by a return of body temperature to euthermic (nonhibernating) levels and by an early rising phase that was indistinguishable from the rising phase of type II responses. This indicates that the rising phase of type II responses and the duplicate portion of full arousals are produced by a common neuronal mechanism that functions as the trigger for arousal from hibernation, and that this mechanism can be spontaneously inhibited when increasing internal temperature reaches a hibernation ceiling level.
Effect of an angiotensin II antagonist on autoregulation in the isolated dog kidney
Authors: Kaloyanides GJ , DiBona GF
Published: December 2017

The effect of the specific angiotensin II antagonist (AIIA), [1-sarcosine-8-alanine]angiotensin II, on autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF) in an isolated dog kidney was examined. Infusing the AIIA into the renal artery at 1.9 mug/min inhibited the renal vasoconstrictor action of angiotension II infused simultaneously at 1.15 mug/min. Under conditions of constant renal arterial pressure the AIIA had no significant effect on sodium excretion, GFR, RBF, cortical blood flow distribution (microsphere method), or renin secretion in non-renin-depleted kidneys. Similarly, no agonist properties were observed when the AIIA was infused into renin-depleted kidneys. This dose of the AIIA did not impair the capacity of the isolated kidney to regulate GFR or RBF when renal arterial pressure was increased from 100 to 150 mmHg. Efficiency of autoregulation of GFR and RBF was 77 and 82% of that predicted for perfect autoregulation. These values are not significantly different from those of the isolated kidney not infused with the antagonist. It is concluded that the angiotensin II antagonist, [1-sarcosine-8-alanine]angiotensin II, has no significant agonist properties, that it antagonizes the renal vascular effects of exogenously administered angiotensin II, but does not impair renal autoregulation. These data provide no support for the hypothesis that the renin-angiotensin system mediates the autoregulation of GFR and RBF.
Paradoxical increased feeding following glucose infusions in recovered lateral rats
Authors: Novin D , Gonzalez MF , Sanderson JD
Published: December 2017

Glucose infusions increased feeding in recovered lateral hypothalamic (LH) lesioned rats in constrast to its suppressant effect in sham-lesioned rats and in rats with lesions unilateral, asymmetrical or anterior to LH. This paradoxical enhancement of eating by glucose was predicted from similar effects seen in vagotomized rabbits and general parallels observed in ingestive behavior after LH lesions and vagotomy. We conclude that an important component in the short-term control of food intake is a vagal-LH circuit and that a modification of the classic notion of the LH as an excitatory "feeding center" is needed.
Effects of maleate on carbohydrate metabolism in rats
Authors: Rogulski J , Pacanis A , Strzelecki T , Kaminska E , Angielski S
Published: December 2017

Intraperitoneal administration of maleate produced an increase in blood alpha-ketoacid, acetoacetate, and free fatty acids. The effect of this treatment on blood glucose levels depended on whether the rats were fed or fasted. In fed rats it was accompanied by slight, transient hyperglycemia connected with depletion of liver glycogen stores. In fasted animals moderate hypoglycemia was observed. The in vivo conversion of various precursors into blood glucose was not inhibited, suggesting that maleate does not affect hepatic gluconeogenesis. Neither was a direct effect on liver glycogenolysis observed. On the other hand, maleate inhibited renal gluconeogenesis from various substrates and stimulated anerobic glycolysis in kidney cortical alices. The data are interpreted in terms of increased utilization and decreased production of glucose by the kidney followed by secondary changes in liver carbohydrate metabolism.
Ouabain-mediated sodium uptake and bile formation by isolated perfused rat liver
Authors: Graf J , Peterlik M
Published: December 2017

Ouabain exhibits a dose-dependent choleretic effect in the isolated perfused rat liver. Its uptake from the perfusate into the liver is maintained against a concentration gradient and becomes clearly saturated at higher perfusate concentrations. A low extracellular sodium concentration inhibits the rate of ouabain transfer into liver cells, resulting in a marked decrease of the maximal transport rate. Dibucaine completely abolishes the uptake of the glycoside by the isolated liver. Determination of Na-22 tracer fluxes suggests that ouabain uptake is accompanied by a net flux of sodium into the cell, which seems to be due to a cotransport of sodium with ouabain rather than to the inhibition of the sinusoidal Na+ -K+ -ATPase. Sodium introduced into the cell in this way apparently is extruded into the bile canaliculi. The increase of isotonic bile flow, which is simultaneously observed, points to a dilution of the canalicular sodium gradient by water and electrolytes through an intercellular pathway. Our results present further evidence that bile secretion is controlled by transcellular sodium movements.
Interaction of interval-force relationship with aortic pressure and stroke volume
Authors: Powers ER , Foster  , Powell WJ
Published: December 2017

The modification by aortic pressure and stroke volume of the response in cardiac performance to increases in heart rate (interval-force relationship) has not been previously studied. To investigate this interaction, 30 adrenergically blocked anesthetized dogs on right heart bypass were studied. At constant low aortic pressure and stroke volume, increasing heart rate (over the entire range 60-180) is associated with a continuously increasing stroke power, decreasing systolic ejection period, and an unchanging left ventricular end-diastolic pressure and circumference. At increased aortic pressure or stroke volume at low rates (60-120), increases in heart rate were associated with an increased performance. However, at increased aortic pressure or stroke volume at high rates (120-180), increases in heart rate were associated with a leveling or decrease in performance. Thus, an increase in aortic pressure or stroke volume results in an accentuation of the improvement in cardiac performance observed with increases in heart rate, but this response is limited to a low heart rate range. Therefore, the hemodynamic response to given increases in heart rate is critically dependent on aortic pressure and stroke volume.
Biliary secretion in elasmobranchs. II. Hepatic uptake and biliary excretion of organic anions
Authors: Boyer JL , Schwarz J , Smith N
Published: December 2017

[35S]Bromosulfophthalein ([35C]BSP), [14C]sodium taurocholate ([14C]NaTC), AND 10 MG OF UNLABELED BSP.and of phenol-3,6-dibromophthalein disulfonate (DBSP) per kilogram body weight were injected in the caudal artery of free-swimming dogfish sharks (Squalus acanthias) and small skates (Raja erinacea). Twenty-four hours later, 85.8 +/- 15.7% of [35S]BSP was recovered in bile and liver in dogfish and 78.4 +/- 9.9% in skates. Similar results were obtained for [14C]NaTC. Unlabeled BSP or DBSP (10 mg/kg body wt) were also selectively excreted in bile over a 4-day period and at comparable rates in both species. More than 85% of [35S]BSP, BSP, and DBSP in bile was in unconjugated form. Selective hepatic clearance of BSP occurred despite nonselective binding to liver homogenates and very low concentrations of binding proteins in liver cytosol. Analysis of the organic anion plasma disappearance curves suggest that the clearance of anions into bile in elasmobranchs is delayed disproportionately relative to hepatic uptake. Albumin-BSP infusions did not prevent selective hepatic uptake of [35S]BSP, although biliary excretion was delayed further. These studies demonstrate that transport systems for biliary excretion of organic anions evolved prior to migration of marine life from the sea and relatively independently of intrahepatic conjugation and organic anion-binding proteins.
Hypophysectomy and regulation of body weight in the genetically obese Zucker rat
Authors: Powley TL , Morton SA
Published: December 2017

Genetically obese Zucker "fatty" rats (fa/fa) and nonobese siblings were weighed regularly from 7 to 150 days of age to determine the onset and time course of the excessive weight gain that characterized the fatty rat. At 150 days of age, male and female fatties and their lean littermates were sham operated or hypophysectomized to examine the role of the pituitary in the fatty obesity. The operated animals were then weighed until sacrifice at 220 days of age, when adrenal weights, gonadal weights, uterine weights, and the Lee Index were determined. Fatty rats were significantly heavier than their nonobese littermates even in the 2nd wk of life (day 7-13). Complete hypophysectomy blocked the continued development of the fatty obesity but did not eliminate the adiposity established prior to hypophysectomy. It is concluded that the pituitary and the major endocrine pathways it controls are not the locus of the primary genetic lesion responsible for maintaining the Zucker fatty rat obesity.
Ultrastructure, calcium accumulation, and contractile response in smooth muscle
Authors: McGuffee LJ , Bagby RM
Published: December 2017

After removing extracellular Ca2+ with [ethylene bis(oxyethylenenitrilo)]tetraacetic acid, we found that the guinea pig vas deferens (VD) was mechanically responsive to electrical stimulation for a significantly greater length of time than was guinea pig taenia coli (TC). An obvious explanation for these findings is that the VD has more intracellular calcium available for contraction than does the TC. To determine if this explanation is plausible, the volume of internal storage structures within the two muscles was compared. It was found that the volumes of potential sequestering structures in the VD and TC are not significantly different. Next, the affinities of the storage structures for calcium were compared. The VD was found to accumulate approximately twice as much 45Ca as did the TC, as determined by 45Ca autoradiography. Calcium-45 was present to a greater extent in association with surface vesicles, sarcoplasmic reticulum (SR), and mitochondria than in the unassociated state within the cytoplasmic matrix. Based on the results of these experiments, we suggest that the VD and the TC of the guinea pig differ in the affinity of their storage sites for calcium.
Neuromuscular function at hyperbaric pressures: pressure-anesthetic interactions
Authors: Kendig JJ , Cohen EN
Published: December 2017

Hydrostatic pressure and anesthetic agents exert mutually antagonistic effects, including pressure reversal of anesthesia and anesthetic amelioration of the high-pressure nervous syndrome. To clarify the cellular basis for these phenomena, twitch tension and electromyogram (EMG) were monitored in the indirectly stimulated isolated rat diaphragm. Compression to 137 atm increased twitch tension without changing EMG amplitude. Partial phrenic nerve block accompanied EMG depression induced by methoxyflurane and chloroform; pressure antagonized these effects. To examine subthreshold pressure effects, calcium concentration was decreased from 2.5 to 0.5 mM. Compression to 137 atm then reversibly decreased EMG amplitude, while enhancing twitch tension. In 0.5 mM calcium, methoxyflurane and chloroform depressed EMG amplitude before blocking phrenic nerve conduction; pressure to 137 atm produced additional depression. These results suggest that pressure enhances twitch tension by acting on excitation-contraction coupling or on the contractile mechanism. They also indicate that pressure may inhibit transmission at the neuromuscular junction, and they do not support synaptic transmission as a site of pressure-anesthetic antagonism.
Evidence for active chloride transport in dogfish rectal gland
Authors: Siegel NJ , Schon DA , Hayslett JP
Published: December 2017

To evaluate the characteristics of the transport process for Na and C1 by the rectal gland of the dogfish shark, experiments were performed with an in vitro perfused model. Changes in glandular secretion rate and net electrical potential difference (PD) were measured during independent alterations of the Na and C1 concentrations of the perfusate solution. The rate of net secretion was enhanced by increasing the concentration of either Na or Cl in the perfusate, demonstrating a substratedependent process. When tetramethyl-ammonium was substituted for Na, the rate of secretion fell in association with a rise in net PD from -8 mV to -17 mV (lumen negative). When SO4 was substituted for Cl, secretion rate also fell, but in association with a fall in net PD. Despite almost complete replacement of Cl with SO4, net PD was not reversed. Although the mechanism responsible for Na secretion remains unclear, these data suggest that chloride is transported by an active process in the dogfish rectal gland.
Intestinal calcium absorption: differences in transport between duodenum and ileum
Authors: Behar J , Kerstein MD
Published: December 2017

The interaction of calcium with sugar, sodium, and water absorption was studied in rats fed laboratory chow and in vitamin D-deficient and -repleted rats with the use of intestinal loops in vivo. Calcium absorption in the duodenum was enhanced by D-glucose only in the vitamin D-deficient state. In both vitamin D-deficient and -repleted ileum, calcium absorption decreased when NaCl was replaced by mannitol; however, it remained unchanged when NaCl was replaced by choline chloride or urea. Calcium absorption was enhanced by actively transported sugars and by increasing net water flow generated by differences in osmotic pressure and urea. Under all experimental conditions there was a strong association between net water and calcium absorption in the ileum. These findings suggest that calcium absorption is enhanced by solvent drag, although the role of sodium cannot be excluded entirely.
De novo synthesis of alanine by the perfused rat hindlimb
Authors: Grubb B
Published: December 2017

Due to the disproportionately large production of alanine by muscle, it has been suggested that part of the alanine released by muscle is synthesized de novo by the transamination of glucose-derived pyruvate. This glucose-alanine conversion was quantitated in the isolated rat hindlimb perfused with a solution of bicarbonate buffer containing 2% albumin, 2.4% dextran, 2.5-15.9 mM glucose, 32-34% dog erythrocytes, and 0.05 muCi/ml [14C]glucose. Measurement of labeled alanine production allowed quantitation of de novo alanine synthesis. De novo derived alanine accounted for an average of 33% of the total alanine released by the perfused tissue (perfusate glucose concentration 8.3 mM), concurrently 2.7% of the glucose taken up by the limb was converted to alanine. By increasing the glucose concentration perfusing the muscle, both the rate of glucose uptake and de novo alanine release were increased. Addition of insulin to the perfusate (700 muU/ml) resulted in a significant increase in the rate of glucose uptake and de novo alanine production, but the rate of total alanine release was significantly decreased by the hormone. It was concluded that de novo alanine production accounts for a sizeable portion of the total alanine released by muscle, nevertheless a comparatively small fraction of the glucose carbons are actually transformed to alanine.
Sympathetic innervation of guinea pig uterus and ovary
Authors: Kulkarni PS , Wakade AR , Kirpekar SM
Published: December 2017

The relative contribution of the ovarian nerves and hypogastric plexus in the innervation of the guinea pig uterus and ovary was assessed. Chronic section of the hypogastric nerve did not reduce norepinephrine (NE) concentration in either organ. Localization of the hypogastric plexus in female guinea pigs was unsuccessful. Crushing the ovarian nerves 1) lowered the NE concentration in the ovary (70%) and in all portions of the uterus (86%), 2) decreased by 80-90% the uterine retention of [3H]NE, and 3) decreased the intensity of fluorescent adrenergic fibers in the uterus. However, the denervated uterus failed to exhibit supersensitivity to NE. In conclusion, sympathetic innervation of the guinea pig uterus and ovary is predominantly via the ovarian nerves, and a minor pathway of innervation may come from hypogastric plexus.
Influence of blood rheology on intrarenal blood flow distribution
Authors: McDonald KM
Published: December 2017

This study examined the effects of hematocrit and colloid-induced changes in blood rheology on renal blood flow (RBF) distribution. Blood viscosity, measured by coneplate viscometry, was raised 65% in anesthetized dogs either by increasing hematocrit or giving isoncotic dextran 500. Blood volume was kept constant and arterial pressure was unchanged. An increase in hematocrit caused either no change in RBF or a slight increase at each cortical level (zones 1-4). However, dextran hyperviscosity caused decreases in all four zones, the most pronounced in zone 1 (8.03-5.19 ml min(-1) g(-1)) and the least in zone 4 (1.63-1.46 ml min(-1) g(-1)). These data suggest either that increased hematocrit has less effect on "apparent viscosity" of blood within the kidney than does plasma colloid or that increased hematocrit causes renal vasodilatation while colloid hyperviscosity does not cause it. Since GFR remained constant in both types of hyperviscosity, it is possible that GFR is the autoregulated variable and the observed changes in RBF distribution and vascular resistance resulted from the changes in afferent and efferent arteriolar resistance required to preserve GFR.
Repetitive extrasystole as an index of vulnerability to ventricular fibrillation
Authors: Matta RJ , Verrier RL , Lown B
Published: December 2017

The assessment of ventricular vulnerability by inducing ventricular fibrillation (VF) presents limitations when neural activity is being investigated, especially in the unanesthetized animal. As repetitive extrasystoles (RE) have been observed to precede the occurrence of VF, it was relevant to determine whether the RE threshold provides a reliable index of cardiac susceptivility to fibrillation. The RE and VF threshold relationships were studied in 32 chloralose-anesthetized dogs during left stellate ganglion stimulation, vagus nerve stimulation, and beta-adrenergic blockage with practolol. The vulnerable period was scanned at 1-ms intervals and at 2-mA increments with a single, 2-ms, constant-current cathodal stimulus; RE and multiple RE were induced reproducibly when 66% and 82%, respectively, of the fibrillatory current was administered. The nadirs for RE and multiple RE were coincident in the cardiac cycle with the vulnerable-period threshold for VF. Stellate and vagal stimulation and beta-adrenergic blockade resulted in comparable changes in RE and VF thresholds and produced equivalent shifts in the cardiac cycle of the RE and VF vulnerable-period nadirs. These observations suggest that RE and VF phenomena share a common electrophysiologic basis and that the RE threshold can be used as an end point for measuring ventricular vulnerability to VF.
Effects of limited food intake on the obese-hyperglycemic syndrome
Authors: Dubuc PU
Published: December 2017

In ob/ob mice a 12-wk period of food restriction led to a reduced rate of somatic growth and a decreased lean body mass, along with small but reliable reductions in systemic immunoreactive insulin levels and evidence of increased insulin sensitivity. However, no effects of limited access to food were noted on the basal hyperglycemia, the elevated percent carcass lipid, or on the significantly higher levels of serum corticoids that occur in obese animals. These data indicate that hyperphagia alone is not responsible for the maintenance of many of the commonly reported characteristics of the obese-hyperglycemic syndrome, but do not exclude the contribution of factors secondary to the quantity of ingested food. Additionally, the present data lend support to recent work suggesting that chronic hyperinsulinemia or an elevated set point of total carcass lipid may be instrumental in the development of this syndrome.
Analysis of inhibitory effect of dopamine on carotid body chemoreceptors in cats
Authors: Sampson SR , Aminoff MJ , Jaffe RA , Vidruk EH
Published: December 2017

The inhibitory effect of dopamine on carotid body chemoreceptors was studied in anesthetized cats to determine whether it was dependent on changes in blood flow in the vicinity of the receptors. The blood supply to the carotid body was isolated, and flow was controlled with a perfusion pump. Single- or few-fiber recordings were made from the peripheral end of the cut carotid sinus nerve in seven cats. The rate of discharge of 68 chemoreceptor strands increased when flow through the carotid body was stopped. This response was reduced or abolished by dopamine in animals ventilated with either room air (15 strands) or a gas mixture of 95% O2 and 5% CO2 (53 strands). These results suggest that dopamine exerts its inhibitory effect primarily through a direct action on the chemoreceptors rather than by a vasomotor effect in the carotid body.
Coronary vascular sympathetic beta-receptor innervation
Authors: Hamilton FN , Feigl EO
Published: December 2017

Recent studies indicate that coronary vessels have alpha- and beta-2-adrenergic receptors and that the alpha receptors are functionally innervated. We studied whether the beta-2-vasodilator receptors are functionally innervated, using a dog in situ modified Langendorff preparation with constant coronary perfusion pressure. The beating, nonworking heart and systemic circulation were supported with a pump oxygenator. Stimulation of the left stellate ganglion increased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values. After beta-1-receptor blockade (practolol, 10 mg/kg), stellate stimulation decreased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values, revealing alpha-receptor vasoconstriction. After the addition of alpha-receptor blockade (Dibozane, 5 mg/kg), stellate stimulation increased coronary blood flow and coronary sinus oxygen tension a small amount from prestimulation values. Finally, after the addition of beta-2-receptor blockade (propranolol, 2 mg/kg), stellate stimulation increased flow and coronary sinus oxygen tension slightly from prestimulation control values. Direct intracoronary injections of isoproterenol, norepinephrine, and epinephrine gave results consistent with the presence of beta-1 myocardial receptors and alpha and beta-2 coronary receptors. We conclude that there is little functional innervation of coronary vascular beta-2 receptors. Intracoronary injections of isoproterenol and epinephrine activated beta-2-receptor coronary vasodilation after beta-1-receptor blockade, but norepinephrine did not.
Insulin kinetics after portal and peripheral injection of [125I] insulin: II. Experiments in the intact dog
Authors: Navalesi R , Pilo A , Ferrannini E
Published: December 2017

Insulin metabolism in man is usually investigated by peripheral injection of the hormone, whereas native insulin undergoes hepatic extraction prior to mixing in the general circulation. To quantify this difference, in 10 dogs [125I] insulin was injected into a peripheral vein, and the initial distribution volume (IDV), the metabolic clearance rate (MCR), and the mean transit time (t) were computed from the plasma disappearance curve of the immunoprecipitable activity. The splenic vein was then cannulated under pentobarbital anesthesia, and the parameters were again computed from the peripheral activity after portal introduction of the tracer. The MCR after portal injection [15.1 +/- (SE) 1.1 ml/min per kg] was greater (P is less than 0.001) than the MCR after peripheral administration (13.4 +/- 0.9 ml/min per kg). Also, IDV was larger (P is less than 0.01) after portal injection (167 +/- 12 vs. 138 +/- 10 ml/kg). Mean transit times did not change significantly. Insulin secretion rate (0.29 +/-0.04 mU/min per kg) and body insulin mass (7.03 +/- 1.5 mU/kg) were also measured. An estimate of hepatic extraction was obtained from the difference between the clearance rate values calculated following portal and peripheral injection. Under our experimental conditions, hepatic retention of insulin was found to be 19.6% (range 9.6-36.2%). The method is recommended for investigations in man.
Effect of substance P on proximal tubular reabsorption in the rat
Authors: Arendshorst WJ , Cook MA , Mills IH
Published: December 2017

Micropuncture and clearance techniques were used simultaneously to determine the effect of substance P on proximal tubular and overall renal function in anesthetized rats. This polypeptide, infused in saline at 50 pg/min into the abdominal aorta above the renal arteries, produced increases in urine flow, 2.7-3.7 mul/min.g kidney wt (P is less than 0.005); urinary sodium concentration, 32-61 meq/liter (P is less than 0.01); and sodium excretion, 89-223 neq/min (P is less than 0.005). Tubular fluid to plasma inulin concentration ratio measured in the last accessible proximal convolution fell from 2.21 to 1.80 (P is less than 0.001), and thus fractional reabsorption was reduced from 54 to 44% (P is less than 0.001). Absolute reabsorption by the proximal convoluted tubule was also reduced 15.5-12.5 nl/min (P is less than 0.025). In a control series of animals, saline alone infused at the same rate did not produce any statistically significant changes in the measured parameters over the same time period. The intrerenal mechanism responsible for the reduction in proximal reabsorption appears to be a tubular one since no consistent or significant changes were observed in kidney or single nephron glomerular filtration rate, renal plasma flow, or intrarenal hydrostatic pressures. No evidence was found to indicate redistribution of filtration rate, or plasma flow, or a reduction in filtration fraction.
Effects of hypoxia and Freon 12 on mechanics of cardiac contraction
Authors: Kilen SM , Harris WS
Published: December 2017

Data are presented which indicate that the mechanism of tension depression and subsequent recovery from dichlorodifluoromethane (Freon 12), an aerosol gas recently described as a potent cardiac depressant agent, differs from that of hypoxia. To analyze these differences, 22 rat papillary muscles, contracting isometrically in a myograph, were studied during and subsequent to 15-min interventions of of hypoxia. Freon 12 with adequate oxygenation, or Freon 12 combined with hypoxia. During each of the three interventions the developed force (F) was markedly depressed, while peak shortening velocity (Vpm) was selectively more depressed by Freon and Freon combined with hypoxia than by hypoxia alone. While hypoxia shortened the time to peak force (TTP) and one-half relaxation time (RT1/2) markedly, Freon 12 with adequate oxygenation slightly shortened RT1/2 (P is less than 0.001) but failed to shorten TTP significantly. In contrast, Freon 12 administered during hypoxia shortened TTP and RT1/2 significantly (P is less than 0.001), more than did hypoxia or Freon 12 alone. Posthypoxic prolongation of TTP and RT1/2 was not seen during recovery from Freon 12. This prolongation was depressed during recovery from Freon 12 given either during hypoxia or during recovery from hypoxia. The results indicate that Freon 12 and hypoxia act synergically, although the mechanisms through which they mediate their actions on myocardial tissue are not identical.
Effect of stretch on passive transport in toad urinary bladder
Authors: Lief PD , Mutz BF , Bank N
Published: December 2017

In order to gain further information about the effect of stretch on the urinary bladder of the toad, transepithelial movement of radioactive sucrose, chloride, and urea was measured across bladder sacs during acute changes in the internal volume. Short-circuit current (SCC) and total tissue conductance (Kt) were also measured in each experiment. It was found that sudden large increases or smaller graded increases in volume resulted in a consistent fall in the tracer permeability (P*) of all three isotopes. However, this fall was due entirely to the larger area term in the calculation of P* rather than any real change in isotope movement. When total diffusion (TD) of each isotope was calculated by a method that eliminated the changes in surface area, it was apparent that stretch produced no significant effects on the transepithelial movement of any of these three molecules. Large stretch also resulted in parallel increases in SCC and Kt in most bladders. We conclude from these observations that the intercellular pathway for sucrose and chloride and the transcellular pathway for urea are unaltered by degrees of stretch that enhance SCC and sodium transport. By inference, the observed increases in Kt appear to represent changes in specific active pathway conductance (Ka), and may relate importantly to the changes in sodium transport.
Function of pituitary-gonadal axis in zinc-deficient rats
Authors: Lei KY , Abbasi A , Prasad AS
Published: December 2017

The role of zinc in gonadal function was investigated in rats. The increases in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were assayed after intravenous administration of synthetic luteinizing-hormone-releasing hormone (LHRH) to zinc-deficient and restricted-fed control rats. Body weight gain, zinc content of testes, and weight of testes were significantly lower in the zinc-deficient rats compared with the controls. The serum LH and FSH response to LHRH administration were higher in the zinc-deficient rats but serum testosterone response was lower in comparison with the restricted-fed controls. These studies indicate a specific effect of zinc on testes and suggest that gonadal function in zinc-deficient state is affected through some alteration of testicular steroidogenesis.
Ionic requirements of proximal tubular sodium transport. I. Bicarbonate and chloride
Authors: Green R. , Giebisch G.
Published: December 2017

Page 1205: R. Green and G. Giebisch. "Ionic requirements of proximal tubular sodium transport. I. Bicarbonate and chloride." Page 1206: Table 1, the sixth column, NaH2PO4, should read "1.55"; the seventh column, Na2HPO4, should read "7.25." Page 1207: Table 2, in the seventh column of values (Normalized change in concn, K), for series j, delete the zero; this was not measured. Page 1209: Table 3, in the third column of values (Flux, K), series j, delete the zero; this was not measured. Pages 1209–1211: in Figs. 3–6, the phosphate composition of the fluids, given on the insets, should read "8.8."
Isohemic blood volume expansion in normal and areflexive dogs
Authors: Cevese A , Guyton AC
Published: December 2017

The hemodynamic and renal responses to rapid intravascular volume expansion (VE) were studied in normal and areflexive dogs. "Isohemic" expansion was performed by infusing autologous blood (averaging 453 ml) thoroughly mixed with the circulating blood. In areflexive dogs cardiac output and arterial pressure doubled immediately after VE and fell back to control within 70 min; in normal dogs the circulatory response was less than one-third as great, but arterial pressure failed to return to control within 120 min. In the areflexive dogs, water, electrolyte, and total osmolar urinary output rose three- to fivefold after VE and declined thereafter, roughly following arterial pressure. In normal dogs the urine flow increased 40% immediately and rose further up to 70% in 60 min. No evidence for a natriuretic hormone was seen. It is concluded that mechanical factors are mainly responsible for the increased excretion of water and solutes after VE. Direct nervous reflexes to the kidney seemed to play a quantitatively minor role in the renal response.
Mitochondria-rich cells of frog skin in transport mechanisms: morphological and kinetic studies on transepithelial excretion of methylene blue
Authors: Ehrenfeld J , Masoni A , Garcia-Romeu F
Published: December 2017

The following study combines histological observations on the localization and density of mitochondria-rich cells with a kinetic study of the part played by these cells in transport phenomena. In the ventral skin, mitochondria-rich cells and granular cells are equally abundant in the first living cell layer. The mitochondria-rich cells were shown to excrete methylene blue [3,9-bis-(dimethylamino)-phenozathionum chloride]. A kinetic study of this excretion across the isolated epithelium of Rana esculenta skin showed that the mechanism of the excretion was a saturable one. An important fraction of methylene blue excretion depends on the absorption of sodium; the absence of this ion, or the inhibition of its transport by ouabain or amiloride, inhibits the excretion of the organic base. The mitochondria-rich cells, however, do not appear to play a determining role in sodium transport.
Thermoregulatory effects of monoamine potentiators and inhibitors in the rat
Authors: Francesconi R , Mager M
Published: December 2017

Exogenously administered monoamines may elicit variable thermoregulatory responses dependent on dosage, species, site of administration, ambient temperature, etc. In an attempt to reconcile several inconsistencies, we have undertaken a series of studies related to monoaminergic control of temperature regulation. Thus, intraventricular administration of serotonin (2.64-26.4 mug) and norepinephrine (3.3-32.8 mug) in rats evoked acute (15-60 min) dose-dependent hypothermic responses (delta Tre = 2 degrees C) that were gradually superseded by significant, more persistent hyperthermia (delta Tre = 1 degreee C). Administration of chlorimipramine or imipramine (total dose 40 mug), even in monoamine-depleted animals, caused long-lasting hyperthermic responses, presumably by the prevention of reuptake of serotonin and norepinephrine at nerve terminals involved in thermoregulation. Pretreatment with the serotonin inhibitor cyproheptadine (4o mug) attenuated the hyperthermia achieved by central administration of chlorimipramine alone. We conclude that both monoamines can act as thermogenic agents under the conditions of these experiments.
Rise in plasma alpha-amino nitrogen concentration in rats eviscerated after colure regulation
Authors: Smith OK
Published: December 2017

Rats were exposed to 4 or 25 degrees C for 6, 12, and 24 h or for longer periods up to 2 wk, then eviscerated. The hourly changes in plasma alpha-amino nitrogen were followed for 4 h after operation, which because of functional removal of the liver allows amino acids released from the extrahepatic tissues to accumulate in the blood. Although cold exposure of tissues to accumulate in the blood. Although cold exposure of 24-h-fasted rats for 6 h before eviscerated resulted in an increased rate of rise of plasma alpha-amino nitrogen postoperatively, the rise was not significantly greater than warm controls until after 12 h of exposure. Thereafter, similar results were obtained whether cold was 12, 24, or 48 h or 14 days duration. Fasting in the cold produced an immediate sharp rise after evisceration so that the concentration was 2 times the control value in 2 h. By contrast, animals allowed to eat adlibitum showed the rise after evisceration but it was progressively smaller in amount as the exposure extended beyond the 1st day. After 5 days there were no longer significant differences from control values. The reduction in rate of rise in plasma alpha-amino nitrogen coincided with cold-induced increases in food intake. The findings support the view that protein metabolism of muscle, the predominant extrahepatic tissue, may participate in thermogenesis when other sources of energy in the body have been depleted.
Influence of medium tonicity on respiration by suspensions of human platelets
Authors: Pickett WC , Cohen P
Published: December 2017

We describe the use of graded decrements of medium osmolarity to progressively unmask respiratory capacities of whole human platelets in suspension. This departure led to the first demonstration that human platelet mitochondria are capable of tightly coupled respiration that responds to addition of mitochondrial substrates, ADP, and inhibitors in a way that other mammalian mitochondria are expected to behave. In 300 mosM media added alpha-glycerophosphate (G3P), succinate, or ADP effected only slight stimulation of base-line O2 consumption. At 180 mosM O2 consumption peaked and was not significantly affected by succinate or ADP. At 80 mosM base-line O2 consumption fell precipitously and was restored by G3P or succinate prior to being raised to its highest levels by ADP. Added NADH had no effect on O2 consumption at 80 mosM but sharply stimulated it when platelet suspensions were exposed to 60 mosM media by pretreatment with distilled water. At 80 mosM, selected compounds that inhibit or uncouple oxidative phosphorylation of isolated mammalian mitochondria from a variety of cells exerted similar influences on while platelets.
Hyperpolarization of thyroid cells in vitro by thyrotropin and cyclic AMP
Authors: Batt R , McKenzie JM
Published: December 2017

With the use of microelectrodes, membrane potential (MP) was measured in mouse thyroid glands in vitro. A basal resting MP of about -39 mV was confirmed. The initial effect of feeding a low-iodine diet (6-12 days) was hyperpolarization, up to -47 m V; chronic low-iodine diet led to depolarization. Low concentrations of thyrotropin (less than 3 mU/ml superfusate) caused hyperpolarization and high ones (greater than 10 mU/ml) led to depolarization. Cyclic AMP (10(-3) M), dibutyryl cyclic AMP (1.2 X 10(-4) M or 1.2 X 10(-3) M) and theophylline (10(-2) or 10(-3) M) caused similar hyperpolarization: D- and DL-propranolol (5 X 10(-5) -5 X 10(-4) M) produced depolarization and inhibited hyperpolarization by thyrotropin. Conclusions are that hyperpolarization is a consequence of short-term increased secretion of thyrotropin in vivo or of low (near physiological) concentrations in vitro; these effects are probably mediated by cyclic AMP. The relationship to and mechanism of depolarization resulting from chronic enhanced endogenous secretion or high in vitro concentrations of thyrotropin are unknown.