Showing papers in "American Journal of Physiology in 1976"
TL;DR: Affinity for a basic amino acid carrier system was demonstrated for arginine, ornithine, and lysine and a third, low-capacity independent carrier system transporting aspartic and glutamic acids was demonstrated.
Abstract: The percentages of 22 14C-labeled amino acids remaining in rat brain 15 s after carotid injection were measured relative to a simultaneously injected diffusible internal standard, 3HOH. The injected solution also contained a nondiffusible internal standard, [113mIn]EDTA to correct for incomplete brain blood compartment washout. Self-inhibition and cross-inhibition was demonstrated by inclusion of unlabeled amino acids and carboxylic acids. All amino acids tested, excluding proline, alanine, and glycine, could be assigned to one, and only one, blood-brain barrier carrier system. The neutral carrier system transported phenylalanine, leucine, tyrosine, isoleucine, methionine, tryptophane, valine, DOPA, cysteine, histidine, threonine, glutamine, asparagine, and serine. Affinity for a basic amino acid carrier system was demonstrated for arginine, ornithine, and lysine. A third, low-capacity independent carrier system transporting aspartic and glutamic acids was demonstrated.
585 citations
TL;DR: It appears probable that the cerebrovascular responses to norepinephrine are dependent on the integrity of the blood-brain barrier, and it is likely that the increase in cerebral blood flow, associated with norpinephrine when it bypasses the barrier, is secondary to an increase in cortex metabolism.
Abstract: The systemic administration of norepinephrine has minimal effects on the cerebral circulation, perhaps due to blood-brain barrier mechanisms. To test hypothesis, the cerebrovascular effects of norepinephrine beyond the blood-brain barrier were studied in anesthetized baboons, Intraventricular norepinephrine (40 mug/kg) resulted in significant increases in cerebral blood flow (40%), cerebral oxygen consumption (21%), and cerebral glucose uptake (153%). Intracarotid hypertonic urea opens the blood-brain barrier by osmotic disruption; Consequent to hypertonic urea, the intracarotid infusion of norepinephrine, 50 ng/kg-min, significantly increase cerebral blood flow (49%), cerebral oxygen consumption (21%), and cerebral glucose uptake (76%), It appears probable that the cerebrovascular responses to norepinephrine are dependent on the integrity of the blood-brain barrier; It is likely that the increase in cerebral blood flow, associated with norepinephrine when it bypasses the barrier, is secondary to an increase in cerebral metabolism.
281 citations
TL;DR: The decrease in muscle RNA on fasting was responsible for the reduced synthesis observed under controlled in vitro conditions, and reduced supply of glucose, insulin, and amino acids may account for the lower rate of synthesis per microgram of RNA demonstrable in vivo.
Abstract: The effects of food deprivation on protein turnover in rat soleus and extensor digitorum longus (EDL) were investigated. Muscles were removed from fed or fasted growing rats, and protein synthesis ...
276 citations
TL;DR: It is demonstrated that intravenous exogenous CCK suppresses feeding in rhesus monkeys and suggested that endogenous CCK has the same effect; they are consistent with the hypothesis that CCK is a satiety signal.
Abstract: Five rhesus monkeys were infused intravenously with partially purified cholecystokinin (CCK) Just prior to a test meal of solid food after overnight food deprivation; CCK produced large, rapid, dos...
269 citations
TL;DR: The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min-1.
Abstract: The extraction of 11C-labeled methanol, ethanol, and isopropanol, as well as 15O-labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by ext...
254 citations
TL;DR: ADH, MX, and AN exert potent yet differential vasoconstricting actions on peripheral beds, and the differential effects on coronary vascular resistance appeared to be due predominantly to a difference in chronotropic and inotropic actions.
Abstract: A comparison was made of the effects of vasopressin (ADH), methoxamine (MX), and angiotensin II (AN) on coronary and left ventricular dynamics, cardiac output, and regional blood flow distribution ...
234 citations
TL;DR: The results suggest that hyperoxia induces an increase in lung "antioxidant" defense capabilities, and this apparent adaptive response may be important in decreasing the susceptibility of lung tissue to continued O2 toxicity.
Abstract: In studies directed at determining the activities of selected enzymes in lung tissue after in vivo exposure to hyperoxia, 70-day-old rats were exposed to 85% or 90% O2 for 1-14 days. After 7 days of exposure to 90% O2 (1atm), superoxide dismutase activities in mitochondrial and cytosolic fractions increased, respectively, to 245 and 145% of control; glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities increased, respectively, to 317, 175, and 413% of control. The levels of reduced glutathione and total nonprotein sulfhydryl compounds were elevated to 195% and 365% of control. Similar changes were observed in rats exposed to 85% O2 for up to 14 days, but to a lesser degree. The changes are interpreted as a reflection of the overall magnitude of oxidant-induced lung injury-reparative processes. The results suggest that hyperoxia induces an increase in lung "antioxidant" defense capabilities. This apparent adaptive response may be important in decreasing the susceptibility of lung tissue to continued O2 toxicity.
223 citations
TL;DR: Findings are consistent with the hypothesis that bile acids are taken up into the hepatocyte by Na+-dependent carrier-mediated transport.
Abstract: The uptake of 14C-labeled cholic, taurocholic, and chenodeoxycholic acid by the perfused rat liver was studied to characterize the mechanism responsible for hepatic uptake of bile acids. A rapid-injection multiple indicator-dilution technique and the three-compartment model of Goresky were employed. The kinetics of hepatic uptake of the three bile acids could be described by the Michaelis-Menten equation. The maximal uptake velocities (Vmax) were 24.9 +/- 2.2 (mean +/- SD), 20.8 +/- 1.2, 1.2, and 11.4 +/- 0.9 nmol/s-g liver for cholic, taurocholic, and chenodeoxycholic acid, respectively. The corresponding apparent half-saturation constants (Km) were 526 +/- 125, 258 +/- 43, and 236 +/- 48 nmol/g liver. Competitive inhibition could be demonstrated between cholate and taurocholate as well as between cholate and chenodeoxycholate. Substitution of 94% of the Na+ in the perfusion medium decreased the Vmax and the apparent Km of taurocholate uptake by 68 and 55%, respectively. These findings are consistent with the hypothesis that bile acids are taken up into the hepatocyte by Na+-dependent carrier-mediated transport.
221 citations
TL;DR: Despite marked falls in pi E during drug infusion, absolute proximal reabsorption was not reduced significantly, due, it is suggested, to the opposing effects of increases in efferent arteriolar plasma flow and interstitial hydraulic pressure.
Abstract: In 23 Munich-Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intra-arteria...
215 citations
TL;DR: It is concluded that the early prandial insulin release reflexly induced by food-related stimuli temporarily enhances the metabolic conditions which provoke feeding.
Abstract: Peripheral blood glucose and immunologically reactive insulin levels were determined in freely moving normal rats which were submitted either to a free oral glucose load or to a gastric administration of the glucose load. Identical determinations were performed in ventromedial hypothalamic nucleus-(VMH) lesioned and vagotomized rats after the same oral intake. It was demonstrated that: 1) a free oral glucose intake was immediately followed by two peaks of insulun release and a resultant decrease in blood glucose; 2) a gastric glucose load resulted in a single peak of insulin release and the concomitant decline in blood glucose; 3) the recorded blood glucose level was the resultant of the insulin-induced hypoglycemia and the postabsorptive hyperglycemia; and 4) the responses were largely exaggerated in VMH-lesioned rats and abolished by vagotomy. It is concluded that the early prandial insulin release reflexly induced by food-related stimuli temporarily enhances the metabolic conditions which provoke feeding.
212 citations
TL;DR: It is argued that the oral cavity plays a major role in the first phase of insulin release, which in its turn seems to be important in the homeostasis of the blood glucose and insulin levels.
Abstract: Blood glucose and insulin levels were measured in undisturbed and free-moving rats. The insulin level rose in the 1st min after the start of food intake; the glucose level began to increase only in the 3rd min if a fluid carbohydrate-rich food was eaten. The insulin release followed a biphasic pattern. If the same quantity of food ingested orally was injected into the stomach in the same time as the animals needed to complete oral ingestion, delayed insulin release could be seen and the second phase of insulin release was exaggerated. The glucose level, which started to rise in the 3rd min, increased much more than during oral ingestion. With respect to insulin release the same phenomena could be observed if carbohydrate-free fluid food was used instead of carbohydrate-rich fluid food. It is argued that the oral cavity plays a major role in the first phase of insulin release, which in its turn seems to be important in the homeostasis of the blood glucose and insulin levels.
TL;DR: Emperor penguins breed during the cold antarctic winter; the males incubate the single egg while fasting for up to 4 mo and losing some 20 kg of their body mass, higher than predicted from general metabolic equations for birds.
Abstract: Emperor penguins breed during the cold antarctic winter. The males incubate the single egg while fasting for up to 4 mo and losing some 20 kg of their body mass. Fasting captive birds under outdoor conditions lost from 0.145 to 0.434 kg day -1. Mean resting metabolic rate, 49.06 W for 24.8 kg body mass, is 7 and 27%, respectively, higher than predicted from general metabolic equations for birds. Minimal thermal conductance, 1.31 W m-2 degrees C-1, is within the range for other birds. The lower critical temperature is about -10 degrees C; this can be related to large body size (20-40 kg) and to body shape, giving a smaller relative surface area than for other birds. Rigidity of the feathers explains why winds of moderate speed (up to 5 m s-1) have little effect on heat loss. At very low temperatures the behavior of huddling close together is essential in reducing metabolic rate. Without this behavior, survival during the long fast (up to four mo) at winter temperatures would be impossible.
TL;DR: Regardless of loading, delta L occurs within the confines of the contractile state-dependent isovolumic force-L relation and where the latter is equivalent to the end-systolic force-length relation.
Abstract: To determine the interrelationships between ejecting and isovolumic force-length relations and the extent to which the left ventricle will shorten, data obtained in 27 isolated, servo-regulated hearts were examined. For each heart a series of contractions, variably loaded (delta L) were derived for a thickwalled sphere and normalized by the cross-sectional area of muscle and length at zero end-diastolic pressure. It was found that within the physiological range examined total and active force were essentially a linear function of initial L with respective increments or reductions in slope produced by positive or negative shifts in contractile state. The force-L relations obtained isovolumically and at end ejection were virtually identical. For a given ejection pressure, end-systolic L was constant, despite variations in filling and therefore independent of initial L and deltaL; moreover, the L to which the ventricle shortened was determined by the course of the systolic force L-relation. Thus, irrespective of loading, delta L occurs within the confines of the contractile state-dependent isovolumic force-L relation and where the latter is equivalent to the end-systolic force-length relation.
TL;DR: The genetic factors are of great importance in the development of stroke as well as hypertension in the SHR, and the genetic factors associated with A3-gene concentration rather than with the level of blood pressure are suggested.
Abstract: Hypertension and stroke in spontaneously hypertensive rats (SHR) were investigated genetically using stroke-prone SHR (A3), stroke-resistant SHR (C) and their hybrids, hybrid of A3 and C (F1), offspring of F1 X F1 (F2), and those of backcrossing of F1 to the respective parental strains, BC(F1 X A3) and BC(F1 X C). The average blood pressure measured without anesthesia increased in the following order during the experimental period: C less than BC (F1 X C) less than F1 approximately F2 less than BC(F1 X A3) less than A3. The F2 represented a wider spread of variation than the F1, with some of the pressure extending into the range of both parental strains. When the drinking water was replaced with a 1% salt solution, the blood pressure increased and the onset of stroke markedly accelerated in all groups of SHR. Under the hypertensive conditions, the incidence of stroke was associated with A3-gene concentration rather than with the level of blood pressure. Similar but less dramatic effects of salt were observed in another series of hybrid groups derived from A3 and normal Wistar-Kyoto rats. These findings suggest that the genetic factors are of great importance in the development of stroke as well as hypertension in the SHR.
TL;DR: Recovery of contractile force lagged behind the decrease in lactate; a given concentration of muscle lactate was associated with a higher contractiles force early during development of fatigue than late during recovery.
Abstract: The relationship between lactic acid concentration and twitch tension was reevaluated in electrically stimulated frog sartorius muscle. In muscles stimulated under anaerobic conditions at a rate of 30 stimuli/MIN CONTRACTILE FORCE DECREASED TO 36% OF THE INITIAL VALUE IN 15 MIN, Concomitantly lactate increased from 3.3 to 18.7 mumol/g of muscle. The correlaiton between the increase in lactate and the decrease in contractile force was significant (r = -0.99, P less than 0.000001). Recovery occurred in two phases. A rapid increase in contractile force, which represented 20% of the total recovery, took place during the first 15 s and occurred concomitantly with an increase in ATP from 3.9 to 4.6 mumol/g. Lactate concentration did not change significantly during this period. The second phase of recovery of contractile force was complete in 50 min. Lactate concentration and contractile force were significatly correlated during recovery (r = -0;92, P less than 0.00001). However, recovery of contractile force lagged behind the decrease in lactate; a given concentration of muscle lactate was associated with a higher contractile force early during development of fatigue than late during recovery.
TL;DR: The less nutritionally balanced the infusion, the less the reduction in food intake, which suggests that some of the residual oral feeding may be due to a specific appetite for missing elements.
Abstract: Unrestrained rats received continuous and discontinuous intravenous infusions of nutritive substances over long periods, and the effects on energy regulation were examined. Oral food intake was decreased by all glucidic infusions, but by less than the theoretical (caloric) value of the infused substances. A residual oral food intake thus persisted when the energy needs were supplied intravenously, and rats with the greater residual intakes gained excessive body weight. The less nutritionally balanced the infusion, the less the reduction in food intake, which suggests that some of the residual oral feeding may be due to a specific appetite for missing elements. The reduction of oral intake became equal to the calories infused when exogenous insulin was coinfused, and results from discontinuous infusions showed a similar trend. A model for the metering of nutrients at the systemic level was proposed; only when substances are metabolized is there a direct effect on feeding control mechanisms.
TL;DR: It is shown that two different types of osmosensitive afferent fibers exist in the hepatic vagus; one is characterized by increasing the frequency of spike discharges responding to higher osmotic pressure, while the other shows the same response to lower osmosis pressure.
Abstract: Rat liver was perfused with Ringer solution through the portal vein by use of a perfusion system which was designed to switch from standard Ringer solution to hypertonic or hypotonic Ringer solution. Neural responses to the osmotic change in the perfusion solutions were analyzed. They showed that two different types of osmosensitive afferent fibers exist in the hepatic vagus; one is characterized by increasing the frequency of spike discharges responding to higher osmotic pressure, while the other shows the same response to lower osmotic pressure. Behavioral changes caused by hepatic vagotomy were also observed. Though no differences could be detected in routine behavior (e.g., daily intakes of food and water, body-weight increase) between the vagotomized and the sham-operated rats, the former lost the ability to adjust urine concentration immediately in response to osmotic changes in the internal environment. These results provide evidence for the hypothesis that hepatic osmoreceptors exist in the rat.
TL;DR: These experiments suggest that central norepinephrine can influence the cerebral circulation primarily through noradrenergic effects on brain metabolism.
Abstract: The influence of brain norepinephrine on cerebral metabolism and blood flow was examined because exogenous norepinephrine, administered in a way that the blood-brain barrier is bypassed, has been s...
TL;DR: Changes in resting myocardial fiber length are of fundamental importance in fetal cardiovascular homeostasis and, within physiologic limits, it is quite clear that the Frank-Starling mechanism is operative and effective in the fetal lamb.
Abstract: The importance of the Frank-Starling mechanism was evaluated in seven chronically instrumented fetal lambs (128-141 days gestation). Continuous determinations of left ventricular (LV) internal dimensions and pressures were obtained while LV end-diastolic diameter (LVEDD) was reduced by superior vena cava occlusion and increased by infusion of fetal blood into left atrium. A highly significant relationship was found to exist between stroke volume and LV extent of shortening (delta D) (r = + 0.99, P less than 0.001). Altering LVEDD from 10,5 to 13mm or LV end-diastolic pressure from 2.5 to 8 mmHg resulted in a 68% augmentation, in delta D. Spontaneous respiratory efforts resulted in frequent beat-to-beat variations in LVEDD and delta D, which maintained cardiac output constant over a wide range of respiratory rates. Moreover, LV output determined by indicator-dilution techniques remained unchanged over a wide range of spontaneous heart rates (114-180 beats/min) as a result of changes in delta D appropriate to alterations in LVEDD. Thus, changes in resting myocardial fiber length are of fundamental importance in fetal cardiovascular homeostasis and, within physiologic limits, it is quite clear that the Frank-Starling mechanism is operative and effective in the fetal lamb;
TL;DR: The osmoregulatory importance of the free amino acid pool in erythrocytes and muscle was a particularly prominent feature in both species and regulation of muscle cell volume was associated with sharp declines in cellular concentrations of total amino acids (ninhydrin-positive materials) and urea.
Abstract: Little skates, Raja erinacea, and stingrays, Dasyatis americana, were gradually transferred over a period of 4-5 days from full strength to approximatley 50% seawater. Plasma and muscle osmolarity ...
TL;DR: Utilization of betaHB by the brain was signficantly governed by permeability, hence the increased permeability in ketotoc states should contribute to glucose sparing and eventually to protein sparing.
Abstract: Transport of beta-hydroxybutyrate (betaHB) into rat brain was estimated from the early rise in brain/serum 14C ratio after subcutaneous injection of [14C]betaHB. Permeability of the D isomer exceed...
TL;DR: 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.
Abstract: The assessment of ventricular vulnerability by inducing ventricular fibrillation (VF) presents limitations when neural activity is being investigated, especially in the unanesthetized animal. As re...
TL;DR: It was concluded that skeletal muscle exhibits a diurnal variation in glycogen content, and that, contrary to accepted belief, fating significantly alters muscle glycogen concentration.
Abstract: To test whether skeletal muscle glycogen concentration is related to food consumption, glycogen content was determined in red (R) and white (W) vastus lateralis and in soleus (S) muscles from six groups of ad libitum-fed rats killed at 4-h intervals and from 24-h-fasted animals killed at 0800 and 1600 h. The animal quarters were illuminated between 0700 and 1900 h. Glycogen values exhibited a peak at 0800 h and a nadir at 2000 h. These changes bore no relationship to blood glucose and lactate or plasma free fatty acids, glucagon, insulin, and corticosterone concentrations. Fasting resulted in reductions of glycogen content of 49% (S), 47% (R), and 29% (W) in animals killed at 0800h, but at 1600h changes were only 23% (RY), 17% (W), and 8% (S). The smaller changes at 1600 h were apparently due to lower glycogen levels in the tissues of the fed animals. It was concluded that skeletal muscle exhibits a diurnal variation in glycogen content, and that, contrary to accepted belief, fating significantly alters muscle glycogen concentration.
TL;DR: The present results are consistent with the possibility that adenosine relaxes vascular smooth muscle by directly altering Ca2+ permeability and/or membrane potential; they do not support a role for cAMP in theadenosine-induced relaxation of vascular smoother muscle.
Abstract: Adenosine relaxed hog carotid media strips contracted with norepinephrine (NE) and potassium (K+). Adenosine (3 X 10(-6)M) was more effective in relaxing the NE contractures than those produced by ...
TL;DR: During exercise there is an increase in levels of glucose-6-phosphate, fructose 6-ph phosphate, and fructose 1,6-diphosphate that, along with the decrease in ATP levels, can account for the increase in glycolytic flux by activation of phosphofructokinase and pyruvate kinase.
Abstract: Concentrations of key metabolites were determined in carp white muscle before exercise and after maximal activity. It was found that the concentration of ATP decreases by about 65%, ADP decreases s...
TL;DR: The data suggest that walking 200 km (from the sea to the rookery and back) requires less than 15% of the energy reserves of a breeding male emperor penguin initially weighing 35 kg.
Abstract: During the antarctic winter emperor penguins (Aptenodytes forsteri) spend up to four mo fasting while they breed at rookeries 80 km or more from the sea, huddling close together in the cold. This breeding cycle makes exceptional demands on their energy reserves, and we therefore studied their thermoregulation and locomotion. Rates of metabolism were measured in five birds (mean body mass, 23.37 kg) at ambient temperatures ranging from 25 to -47 degrees C. Between 20 and -10 degrees C the metabolic rate (standard metabolic rate (SMR)) remained neraly constant, about 42.9 W. Below -10 degrees C metabolic rate increased lineraly with decreasing ambient temperature and at -47 degrees C it was 70% above the SMR. Mean thermal conductance below -10 degrees C was 1.57 W m-2 degrees C-1. Metabolic rate during treadmill walking increased linearly with increasing speed. Our data suggest that walking 200 km (from the sea to the rookery and back) requires less than 15% of the energy reserves of a breeding male emperor penguin initially weighing 35 kg. The high energy requirement for thermoregulation (about 85%) would, in the absence of huddling, probably exceed the total energy reserves.
TL;DR: The intracellular pH of giant barnacle muscle fibers was measured with glass microelectrodes and also calculated from the distribution of 5,5-dimethyl-2,4-oxazolidinedione and methylamine, and a detailed study of the apparent dissociation constant of DMO as affected by temperature, and ionic strength and composition is included.
Abstract: The intracellular pH (pHi) of giant barnacle muscle fibers was measured with glass microelectrodes and also calculated from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO) and methylami
TL;DR: Placental AIB uptake previously has been shown to increase with preincubation of tissue in vitro, but this increase has now been found to be limited to the A system, demonstrating that the transport pathways are separately regulated.
Abstract: The human placenta is known to concentrate nearly all amino acids intracellularly for transfer to the fetus. To clarify the mechanism and regulation of this process we have determined the specifici...
TL;DR: It is concluded that kininogenases are secreted into the urine at the level of the distal nephron by either the tubule itself or by a specialized structure located at this part of the nephrons, such as the macula densa.
Abstract: We determined the site of kininogenase secretion in the nephron by performing stop-flow studies in dogs. Kininogenase activity, inulin, sodium, and potassium were measured in the same fractions. The highest kininogenase concentration was found in the fractions with the lowest sodium concentration corresponding to urine samples that must have been trapped in the distal nephron. Kininogenases in these urine fractions were 5-17 times higher than in fractions from the proximal nephron or from the free-flow sample. The ratio of kininogenase increase to inulin increase was always higher than 3.0, thus indicating that the increase in kininogenase concentration was mainly due to secretion and not to water reabsorption. When a peak of potassium was present, it occurred 1-2 ml before the peak of kininogenases. We concluded that kininogenases are secreted into the urine at the level of the distal nephron by either the tubule itself or by a specialized structure located at this part of the nephron, such as the macula densa.
TL;DR: In experiments with increasing concentrations of Galactose in hepatocyte water and approximately saturated elimination rates, the concentrations of galactose 1-phosphate, UDPgalactose, and UDPglucose remained essentially constant, indicating that the phosphorylation of galACTose to galactOSE 1- phosphate is the rate-determining process.
Abstract: The relation between galactose elimination rates and blood concentrations in the isolated perfused pig liver was analyzed by a mathematical kinetic model. It assumes that the substrate, under stead...