bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic clearance of renin after angiotensin blockade
Authors: Keiser J. A. , Opgenorth T. J. , Romero J. C.
Published: December 2017

Several investigators have reported that hepatic metabolism of renin can be altered in pathophysiological states (e.g., high-output heart failure, cirrhosis, acute metal toxicity). The hypothesis that circulating angiotensin II may play a role in regulating renin metabolism by the liver was tested in anesthetized dogs. Captopril (SQ 14255) or an angiotensin II-competitive antagonist [( Sar1-Ile8]angiotensin II) was used for blockade of the renin-angiotensin system in two separate groups of dogs. The administration of captopril resulted in a significant fall in the percent extraction of renin by the liver (P less than 0.01) and in the clearance of renin (P less than 0.05). The group receiving the competitive antagonist and time-control animals showed no significant change in renin extraction or renin clearance by the liver. Our data do not support a role for angiotensin II in the regulation of hepatic metabolism of renin, since experiments utilizing the antagonist failed to produce a change. The mechanism by which captopril alters renin metabolism appears to be independent of its blockade of angiotensin II.
Altered plasma insulin and glucose after obesity-producing bipiperidyl brain lesions
Authors: Berthoud H. R. , Powley T. L.
Published: December 2017

A single systemic injection of bipiperidyl mustard (BPM) in the adult rat produces brain lesions and associated obesity without hyperphagia. To characterize some endocrine-metabolic aspects of the BPM preparation we measured plasma insulin and glucose dynamics as well as glucoprivic feeding. BPM-treated animals with verified lesions of the medial portion of the solitary tract nucleus (NTS) and the medial pole of the dorsal motor nucleus of the vagus (DMNX), as well as small lesions affecting the arcuate nucleus and basomedial portion of the ventromedial nucleus of the hypothalamus, showed the following characteristics: normal basal glycemia and insulinemia, exaggerated plasma insulin responses to oral or intravenous glucose and to oral saccharin, increased plasma glucose levels after oral glucose, unimpaired feeding to 2-deoxy-D-glucose challenge, decreased short-term intake of highly palatable food, and 36% more body fat at the end of the experiment. None of these changes occurred in rats that failed to develop lesions after BPM administration. These results suggest that BPM lesions (which appear to overlap distributions of central insulin binding sites) both affect a central mechanism controlling the pancreatic beta-cells and possibly influence gastric emptying and/or intestinal glucose absorption.
Attenuation of postexercise ketosis in fasted endurance-trained rats
Authors: Beattie M. A. , Winder W. W.
Published: December 2017

Endurance-trained animals and human subjects have been reported to exhibit a lesser degree of postexercise ketosis than nontrained controls. We have studied the mechanism of this adaptation. Trained (2 h/day, 6 wk) and nontrained rats were fasted overnight and then run at 16 m/min up a 15% grade for 90 min. Trained rats had lower blood 3-hydroxybutyrate during exercise and during a 90-min postexercise period than nontrained rats. Liver malonyl coenzyme A (CoA), carnitine, and glycogen were not significantly different in the two groups at any time during and after exercise. Therefore these factors cannot be responsible for the difference in ketonemia. Plasma free-fatty acids and hepatic adenosine 3',5'-cyclic monophosphate were elevated in nontrained rats with respect to trained rats. These two differences could conceivably be responsible for a different ketogenic rate. In addition, 3-ketoacid CoA transferase activity of gastrocnemius muscle was increased by training. The increase in ketone oxidizing enzymes of muscle may also be partially responsible for the training-induced attenuation of postexercise ketonemia in these fasted rats.
Glucose transport by lobster hepatopancreatic brush-border membrane vesicles
Authors: Ahearn G. A. , Grover M. L. , Dunn R. E.
Published: December 2017

Epithelial brush-border membrane vesicles (BBMV) were made from lobster hepatopancreas by using Mg2+ precipitation. Alkaline phosphatase, Na+-K+-ATPase, and cytochrome c oxidase activities in these vesicles were enriched 15.0-, 1.0-, and 0.19-fold, respectively, compared with activities of a washed original homogenate pellet, indicating a relatively pure apical membrane preparation reduced in basolateral or organelle contamination. Complete vesicular closure was confirmed with electron microscopy and equilibrium [3H]D-glucose uptake experiments using various transmembrane osmotic gradients. Glucose uptake was stimulated by a transmembrane Na+ gradient but not by an identical K+ gradient or by a Na+ gradient in the presence of phloridzin. Electrogenicity of Na+-dependent glucose transport was confirmed in two ways. First, an anion permeability sequence indicated glucose uptake was stimulated in the following order: SCN- greater than Cl- greater than gluconate- greater than SO4(2-). Second, an outwardly directed valinomycin-induced K+ diffusion potential, rendering the vesicle interior electrically negative, enhanced glucose uptake compared with K+-loaded vesicles lacking the ionophore. Glucose influx occurred by a combination of carrier-mediated transfer, illustrating Michaelis-Menten kinetics, and nonsaturable “apparent diffusion.” pH (same on both sides) strongly influenced Na+-dependent glucose uptake according to the sequence: pH 6.0 greater than pH 7.4 greater than pH 8.0. Increased proton concentration lowered the Michaelis constant for glucose transport and increased the apparent diffusional permeability of the membrane to the sugar. Maximal carrier-mediated glucose transport rate was largely unaffected by pH.(ABSTRACT TRUNCATED AT 250 WORDS)
Endogenous renin-angiotensin system and drinking behavior in flounder
Authors: Balment R. J. , Carrick S.
Published: December 2017

High rates of drinking in seawater-adapted, compared with freshwater (FW)-adapted, flounder were associated with raised plasma chloride and osmotic concentrations. Hypotension in FW-adapted fish, after papaverine administration, gave rise to greatly elevated rates of drinking. This dipsogenic response apparently relied on activation of the endogenous renin-angiotensin system (RAS) and was abolished by simultaneous administration of the converting enzyme inhibitor, captopril. Exogenous angiotensin II was shown to be dipsogenic and vasopressor in the FW-adapted fish. The physiological importance of the activation of the RAS in the control of drinking behavior in euryhaline fish is discussed.
Differential effects of food restriction on pituitary-testicular function in mice
Authors: Blank J. L. , Desjardins C.
Published: December 2017

The reproductive responses of two species of wild rodents, house mice and deer mice, were evaluated following a 30% reduction in food intake for 5 wk. These animal models were chosen as prototypes of other rodent species because each employs unique functional adjustments when confronted with reduced resources in their natural habitats. Modest inanition failed to alter pituitary-testicular function in house mice; neither spermatogenesis nor plasma concentrations of luteinizing hormone (LH) and testosterone were modified. In sharp distinction, deer mice exposed to restricted food intake showed significant reductions in plasma LH and testosterone and an accompanying loss in spermatogenesis. Reduced food intake also caused pronounced shifts in the temporal organization and amount of wheel-running activity in both animal models, albeit in a dichotomous fashion. House mice exhibited the same amount of wheel-running activity throughout inanition, but the diel periodicity of locomotor behavior was shifted from the dark to the light period. Deer mice, in comparison, significantly curtailed wheel-running activity during the dark hours but ran in precise phase relationship with the light-dark cycle. Taken together, our results establish that the male reproductive system and its supporting neuroendocrine and behavioral correlates can be disrupted by modest levels of food restriction in certain animal models.
Activation of hypothalamo-hypophysial-interrenal system by urophysectomy in goldfish
Authors: Woo N. Y. , Hontela A. , Fryer J. N. , Kobayashi Y. , Lederis K.
Published: December 2017

Plasma cortisol, pituitary adrenocorticotropin and arginine vasotocin (AVT) contents, and hypothalamic urotensin I (UI) and AVT contents were determined in urophysectomized goldfish (1 wk) with and without dexamethasone injections. Urophysectomy produced marked increases in plasma cortisol. These marked increases could not be observed in urophysectomized fish that received dexamethasone injections. These findings suggest that the hypothalamo-pituitary-interrenal axis is activated after urophysectomy. This activation may be due to the enhanced secretion of U I from the goldfish hypothalamus, suggesting that U I may be a fish corticotropin-releasing factor.
Extraretinal photoreception in the lizard Sceloporus occidentalis: phase response curve
Authors: Underwood H.
Published: December 2017

All submammalian vertebrates have extraretinal photoreceptors (ERR) that can mediate entrainment of circadian rhythms to 24-h light-dark (LD) cycles. Phase response curves (PRC) for 6-h fluorescent light pulses were generated for lizards (Sceloporus occidentalis) previously subjected to sectioning of both optic nerves (ONX). The PRC for ONX lizards (only ERRs present) shows a threefold increase in the amplitude of both the advance and delay portions of the PRC compared with a PRC previously generated for sighted S. occidentalis. Also, in contrast to sighted lizards the area of the advance part of the PRC of ONX lizards is greater than the delay portion. Consistent with the shape of the respective PRCs in ONX vs. sighted lizards are the following facts. 1) The range of entrainment to LD cycles is greater in ONX lizards; some sighted lizards free-ran when exposed to LD 6:21.5 or LD 6:23.5 but entrained after ONX lizards reentrained to an 8-h shift in the phase of a LD 6:18 cycle significantly faster than sighted lizards. 3) Forty-two percent of ONX lizards showed a shorter free-running period (tau) in LL than DD, whereas 90% of sighted lizards showed a longer free-running period in LL than in DD. In those lizards in which tau LL greater than tau DD, the the average tau change in ONX lizards in was significantly less than that observed in sighted lizards. These results are consistent with the hypothesis that the eyes have an "inhibitory" role in the circadian system of S. occidentalis.
Glucose kinetics and body temperature after lethal and nonlethal doses of endotoxin
Authors: Lang C. H. , Bagby G. J. , Spitzer J. J.
Published: December 2017

Rats were injected with doses of endotoxin ranging from 1,000 [lethal dose approximately 50% (LD50)] to 0.01 microgram/100 g, and alterations in hemodynamics, glucose kinetics, and body temperature were studied over the subsequent 4 h. Doses of 10 micrograms/100 g or less were consistently nonlethal over 72 h. Decreases in arterial blood pressure and cardiac output were evident in rats receiving 1,000-10 micrograms/100 g endotoxin. Doses of endotoxin between 1,000 and 10 micrograms produced an early hyperlactacidemia evident by 1 h, whereas the lower doses (1 and 0.1 microgram) induced elevations that exhibited a delayed temporal response. The rates of glucose appearance (Ra) and disappearance (Rd) were increased early and transiently by the higher doses of endotoxin. Lower doses increased glucose Ra and Rd between 2 and 4 h after endotoxin. A febrile response was elicited by 10, 1, and 0.1 microgram/100 g endotoxin, while hypothermia was seen in animals receiving higher doses. Thus high doses of endotoxin induced metabolic and hemodynamic alterations that were temporally associated. Very low nonlethal doses of endotoxin (up to 4 orders of magnitude less than LD50) induced metabolic changes that appeared to be independent of hemodynamic disturbances but were temporally associated with the observed hyperthermia.
Renal response to atrial natriuretic factor in conscious dogs with caval constriction
Authors: Freeman R. H. , Davis J. O. , Vari R. C.
Published: December 2017

Constriction of the thoracic inferior vena cava to decrease venous return and atrial filling markedly elevates plasma renin activity (PRA) and plasma aldosterone concentration (PAC) and produces chronic sodium retention and ascites in the dog. Infusion of a synthetic atrial natriuretic factor into conscious dogs with caval constriction and ascites at doses of 175 and 350 ng X kg-1 X min-1 for 30 min each produced striking increases (P less than 0.05) in creatinine clearance, diuresis, and kaliuresis but failed to increase urinary sodium excretion. Infusions of atrial natriuretic factor at these doses into conscious normal dogs, however, produced a striking increase in sodium excretion from 41 +/- 14 and 55 +/- 19 mu eq/min to 150 +/- 58 and 181 +/- 49 mu eq/min (P less than 0.05 for both values). Creatinine clearance and urine flow also increased in these normal dogs, but potassium excretion remained unchanged during the infusion periods. Atrial natriuretic factor produced parallel suppression (P less than 0.05) of the elevated levels of PRA and PAC in the caval dogs but failed to significantly decrease either PRA or PAC in the normal animals. Arterial pressure, heart rate, and PAH clearance were unchanged in both groups of dogs during infusion of atrial natriuretic factor. These results suggest that the pattern of renal electrolyte excretion elicited in response to the acute infusion of atrial natriuretic factor is dependent, at least partially, on the preexisting status of the renal tubules to facilitate sodium reabsorption and potassium excretion. The results also are consistent with the concept that atrial natriuretic factor might function to tonically inhibit the renin-angiotensin-aldosterone system.
Oxygen transport in invertebrates
Authors: Mangum C. P.
Published: December 2017

The distribution of the O2 carrying proteins suggests that the original transport system was a hemoglobin similar to the alpha-chain of hemoglobin A and packaged in a nucleated red blood cell. These molecules, which occur in large open fluid compartments, function as O2 stores for regular periods of hypoxia as well as carriers between sites of gas exchange. When the closed circulatory system first arose, the red blood cell was abandoned in favor of extracellular heme proteins, and the O2 storage function became less important. Alternative O2 carriers, hemerythrins, appear in the blood at about the same phylogenetic level as the intracellular hemoglobins, and their respiratory functions appear to be similar. The presence of hemoglobins instead of hemerythrins in the vertebrates may be an evolutionary accident. Still other O2 carriers, hemocyanins, arose separately in two specialized groups that left no descendants. Their O2 binding has all the adaptive features of vertebrate hemoglobin O2 binding, with unique features also. The respiratory function of the hemocyanins is largely limited to O2 transport, which makes a far greater contribution to aerobic metabolism than the O2 carriers found in simpler systems.
Endotoxin alters biochemical and morphological responses to pneumonectomy in adult rats
Authors: Sosenko I. R. , Frank L.
Published: December 2017

Adult rats treated with endotoxin, like untreated neonatal rats, are resistant to O2 toxicity and manifest very similar lung biochemical responses. We hypothesized that endotoxin might also alter the adult pneumonectomy response to resemble the accelerated response of younger animals. Adult and 19-day rats underwent pneumonectomy, followed in 24 h by endotoxin or saline injection. Pneumonectomized rats, shams, and controls were killed 72 h after surgery for lung biochemistry and morphometry. Compared with adult saline-pneumonectomized rats, adult endotoxin-pneumonectomized rats, adult endotoxin-pneumonectomized rats demonstrated a significantly greater growth response and a lung biochemical response pattern (increased RNA, markedly increased RNA/DNA) similar to 19-day rats. Morphologically, endotoxin-pneumonectomized rats showed a different pattern of lung regrowth (significantly larger air spaces). Saline pressure-volume curves were not different between the two groups. We conclude that endotoxin administration to pneumonectomized adult rats resulted in accelerated lung regrowth, a lung biochemical response pattern similar to 19-day rats, but a paradoxical morphological pattern resembling more closely that of the adult than the neonatal animal.
Pulmonary vascular resistance during unilateral pulmonary arterial occlusion in ducks
Authors: Powell F. L. , Hastings R. H. , Mazzone R. W.
Published: December 2017

We measured mean pulmonary arterial pressure (Ppa) during temporary unilateral pulmonary arterial occlusion (TUPAO) in 10 ducks. Ppa increased from 11.4 +/- 0.8 mmHg during control conditions to 18.8 +/- 1.8 during TUPAO. In 5 of the 10 ducks we also measured mean left atrial pressure (Pla) and cardiac output (Q). In these ducks Ppa significantly increased with TUPAO from 13.9 +/- 0.4 to 22.0 +/- 1.2 mmHg, whereas Pla and Q did not change significantly. Pulmonary vascular resistance (PVR) increased from 10.6 +/- 1.3 to 24.1 +/- 5.3 mmHg X min X 1(-1) on TUPAO. By assuming equal vascular resistance in either lung it can be calculated that the vascular resistance in only one lung was 22.5 +/- 3.5 mmHg X min X 1(-1) during control conditions. Thus doubling flow resulted in no significant change in one lung's vascular resistance. A morphometric study of both lungs of a domestic goose that were rapidly frozen during TUPAO indicated very little compliance in pulmonary blood capillaries. The relative volume of exchange tissue occupied by blood capillaries was 0.28 in the occluded lung and 0.36 in the perfused lung. Surface-to-volume ratios of blood capillaries were 12,524 cm-1 in the occluded lung and 11,056 cm-1 in the perfused lung. We conclude that PVR in birds is relatively insensitive to changes in Q, in contrast to mammals.
Food intake in diabetic rats: isolation of primary metabolic effects of fat feeding
Authors: Friedman M. I. , Ramirez I. , Edens N. K. , Granneman J.
Published: December 2017

The effects of varying dietary fat content on food intake and metabolism in streptozotocin-diabetic rats were examined. The metabolic consequences of fat feeding were separated from the marked adjustments in voluntary food consumption that occur when diabetic rats are fed diets containing different amounts of fat by feeding rats a fixed ration of food in which either fats or carbohydrates were reduced by equicaloric amounts, or in which only the concentration of fat, but not other dietary nutrients, was varied systematically. Resulting changes in metabolism and subsequent ad libitum food intake on refeeding were then measured. Rats did not increase their food intake after a prior reduction in carbohydrate consumption but did so after an equicaloric reduction in fat consumption. Urinary glucose excretion during rationing was a function of carbohydrate consumption and was not predictive of changes in food intake during refeeding. The more fat that rats consumed during rationing, the higher their levels of plasma triglycerides and ketone bodies were at the time of refeeding and the less they ate when allowed to eat ad libitum. The orderly changes in food consumption and in plasma triglycerides and ketones observed with variations in fat intake suggest that the effects of fat feeding on food intake in diabetic rats are mediated through the oxidation of ingested fat.
Isolated perfused head of rainbow trout. I. Gas transfer, acid-base balance, and hemodynamics
Authors: Perry S. F. , Booth C. E. , McDonald D. G.
Published: December 2017

Branchial gas transfer, acid-base balance, and hemodynamics were critically evaluated and compared in Ringer-perfused and blood-perfused heads of rainbow trout. Blood perfusion stimulated O2 uptake and CO2 excretion across the gills to values more representative of intact fish. The stimulatory effect of blood on gas transfer was due to increased O2 carrying capacity (O2 uptake) and the presence of erythrocytic carbonic anhydrase (CO2 excretion). Adding carbonic anhydrase to Ringer enhanced CO2 excretion in a manner similar to blood. During Ringer perfusion, arteriovenous pH gradients were abnormal (arterial pH less than venous pH). Perfusion with blood or addition of carbonic anhydrase to Ringer reversed the pH gradients to typical in vivo levels. Branchial vascular resistance to flow was abnormally high in both Ringer- and blood-perfused preparations, primarily as a result of low dorsal aortic pressure. Input pressure increased during blood perfusion and was similar to ventral aortic pressure in vivo. Perfusion with Ringer may have caused irreversible deterioration of gill function as indicated by decreased arterial Po2 and O2 extraction effectiveness after a rapid switch from Ringer to blood perfusion. The results are discussed with reference to the suitability of perfused trout head preparations for studying gill gas transfer, acid-base balance, and hemodynamics. Comparisons are made between the perfused head preparation and intact fish as well as with other types of perfused gill preparations.
Effect of pregestational sialoadenectomy of nursing mothers on eyelid opening of pups
Authors: Okamoto S. , Oka T.
Published: December 2017

The eyelid opening of pups born to and nursed by normal mice occurred by the 15th day of birth, whereas pregestational sialoadenectomy (removal of submandibular glands) of nursing mice delayed eyelid opening of their pups by as much as 5 days. Parotidectomy, however, had no effect on eyelid opening. Cross-foster nursing experiments indicated that the cause for delayed eyelid opening of pups was to be found in sialoadenectomized mothers, not their pups. Sialoadenectomized mothers had underdeveloped mammary glands that produced approximately 50% less milk than controls, and the amount of epidermal growth factor in their milk was similarly reduced. When epidermal growth factor, a polypeptide produced by the submandibular gland, was injected daily at a dose of 5 micrograms into sialoadenectomized pregnant mice, the eyelid opening of the pups nursed by their mothers occurred normally. These results are discussed with regard to the possible role of the submandibular gland and epidermal growth factor in neonatal eyelid opening.
Metabolic mapping of a cardiac reflex mediated by sympathetic ganglia in dogs
Authors: Kostreva D. R. , Armour J. A. , Bosnjak Z. J.
Published: December 2017

The hypothesis tested was that some cardiac reflexes can be mediated by the neural mechanisms in thoracic sympathetic ganglia in addition to those existing in the spinal cord or brain stem. In mongrel dogs anesthetized with pentobarbital sodium the left stellate (SG) and middle cervical (MCG) ganglion were decentralized, and the left thoracic vagosympathetic trunk was cut cranial to the MCG and caudal to the MCG but above the heart. The left thoracic vagosympathetic trunk below the MCG was then stimulated afferently. A single bolus of 2-[14C]deoxyglucose was injected intravenously and the stimuli repeated periodically toward the decentralized ganglia for 45 min. The heart and ganglia were then removed, frozen, and sectioned for autoradiography. Significant increases in glucose utilization were found in both the SG and MCG compared with ganglia from nonstimulated control animals. Significant increases in the glucose utilization of the endocardial third of the left ventricle were also observed in the reflexly stimulated hearts. Neural mechanisms in the acutely decentralized SG and MCG could modify cardiac glucose utilization within specific areas of the heart. In addition, such ganglionic mechanisms may be concentrated within the caudal half of the SG. These data suggest that many neurons in the thoracic autonomic ganglia may be involved in local cardiac reflexes.
Propagation of pressure pulse in kangaroo arterial system
Authors: Avolio A. P. , Nichols W. W. , O'Rourke M. F.
Published: December 2017

The pressure pulse contour in the ascending aorta of kangaroos is markedly different from that seen in other species, but the changes undergone by the pulse propagating along the aorta are quite similar. Alteration of wave contour and progressive amplification of the pulse in the distal aorta and peripheral arteries of other mammals have been attributed to elastic nonuniformity of the aorta and to peripheral wave reflection. In kangaroos the aorta approximates a uniform tube with essentially constant viscoelastic properties, whereas wave reflection from the lower body appears to be unusually intense and to emanate from a single functionally discrete reflecting site; this appears to be the result of arterial terminations in the muscular lower body. Intense wave reflection from the lower body is the dominant mechanism responsible for changes in the pressure pulse of kangaroos between the ascending aorta and peripheral arteries. Contour of the pulse in the ascending aorta is attributable to this and to close proximity of reflecting sites in the upper body.
Direction of uterine contractions during estrus in ewes: a reevaluation
Authors: Toutain P. L. , Marnet P. G. , Laurentie M. P. , Garcia-Villar R. , Ruckebusch Y.
Published: December 2017

In four ewes direction of propagation of uterine contractions was evaluated using an electromyographic technique during 15 entire estrous periods; 120,101 propagations were analyzed. When horns were considered separately 89.9% of all propagations were classified into three main modes: ascending (34.3%), descending (59.85%), and divergent (5.85%). When both horns were analyzed simultaneously, horn's synchronicity was observed in most instances; on this basis, eight modes of propagation were identified of which three accounted for two-thirds of all propagation: synchronous descending (24.9%), reciprocal propagation (descending on one horn and then ascending on contralateral horn) (22.1%), and isolated descending propagation (18.0%). A time-dependent pattern of propagation throughout estrus was clearly identified, the percentage of ascending propagations reaching a minimum (16.5%) and the percentage of descending propagation reaching a maximum (77%) at peak uterine motility level. By considering both direction of uterine propagation and cervical mechanical activity, a new hypothesis concerning two aspects of sperm transport (speed and mechanism) was formulated. It is hypothesized that the high prevalence of descending propagations is important to reduce sperm cell population by selecting the most vigorous spermatozoa; such selection is possible when the mechanical cervical activity is low or absent (cervix open); when cervical mechanical activity is high (cervix closed), it is suggested that both descending and ascending propagations participate in sperm transport by back and forth motion of luminal fluid within the uterine lumen.
Nutrient control of cardiac rate in infant rats: role of arterial baroreceptors
Authors: Hofer M. A.
Published: December 2017

A surgical procedure is described for the deafferentation of carotid sinus (CS) and aortic depressor (AD) baroreceptors in 2-wk suckling rats. Baroreflex testing in unanesthetized pups showed that cardiac rate responses to acute elevations of blood pressure were reduced to less than 9% of controls after combined denervation (CSAD), 28% after AD and 47% after CS denervation at 4 h. After 24 h of nutrient deprivation, resting cardiac rates of sham operated controls fell a mean of -148 beat/min, significantly more than CS, AD, or CSAD groups (P less than 0.01). Baroreflex test responses in individuals correlated significantly with their later responses to nutrient deprivation (r = 0.67, P less than 0.01). There were no significant differences in base-line cardiac rate, systolic blood pressure, or cardiac rate during 24 h intragastric milk infusion between deafferented and control pups. These experiments suggest that arterial baroreceptors are important in the cardiovascular adjustments after nutrient deprivation in suckling rats.
Ketone body metabolism in a ground squirrel during hibernation and fasting
Authors: Krilowicz B. L.
Published: December 2017

Hibernating Belding's ground squirrels (Spermophilus beldingi) are ketotic relative to fed nonhibernators. Muscles from torpid individuals, when incubated in media containing physiological concentrations of glucose and ketone, show reduced uptake of glucose in the presence of ketone. The magnitude of the reduction is dependent on ketone concentration and reaches 60% in heart and 100% in pectoralis at 1.4 mM ketone. Fasted squirrels are also ketotic. However, ketone does not reduce glucose uptake in muscles from fed or fasted animals. Glucose utilization by muscles decreases during a long-term fast, but the reduction is independent of ketone. Thus both a long-term fast and hibernation lead to changes in muscle tissues that decrease their reliance on glucose as an energy source. Ketosis leads to glucose sparing during hibernation, whereas muscle glucose utilization is decreased independently of ketone during a fast. The glucose sparing achieved in both hibernation and fasting leads to conservation of body protein, the major source of gluconeogenic precursors in fasting mammals.
Restriction of gut-derived endotoxin impairs DNA synthesis for liver regeneration
Authors: Cornell R. P.
Published: December 2017

The influence of restricting gut-derived endotoxin availability on liver regeneration after partial hepatectomy was evaluated. Partial hepatectomy was performed by 67% liver resection of ether-anesthetized rats. Liver regeneration was quantified after partial hepatectomy by [3H]thymidine incorporation into hepatic DNA; endotoxemia due to absorption of endogenous endotoxin from the gut into the portal circulation was determined by qualitative lysate assay of perchloric acid-extracted plasma samples, and plasma levels of the hepatotrophic factors insulin and glucagon were measured by radioimmunoassay. Treatments to restrict gut-derived endotoxin included chronic gavage with neomycin and cefazolin for gut sterilization, chronic gavage with cholestyramine to bind endotoxin within the gut, subcutaneous administration of polymyxin B to neutralize the lipid A portion of circulating endotoxin, intraperitoneal induction of endotoxin tolerance by progressively higher doses of endotoxin, and experimentation with isolator-reared defined flora Fisher rats that were Gram-negative bacteria deficient and therefore endotoxin deficient. All treatments to restrict endogenous endotoxin impaired DNA synthesis in regenerating livers particularly 21 h posthepatectomy when replication was increasing most rapidly in normal rats. We hypothesize that impairment of DNA synthesis after partial hepatectomy in endotoxin-restricted animals was due to the observed lack of normal systemic endotoxemic as well as hyperinsulinemic and hyperglucagonemic responses to 67% liver resection.
Formulating and evaluating quantitative models of control of sodium stores
Authors: Daniels F. H. , Cortell S. , Leonard E. F.
Published: December 2017

Numerous factors that influence sodium handling have been identified, and many have been studied in minute detail; however, relatively little information is available regarding either the steady-state relationship between dietary sodium intake and sodium stores or the transient response of intact animals to challenges to sodium homeostasis. In this paper the principles of elementary feedback control theory have been used both to obtain and analyze quantitative models of the feedback control of sodium stores. It has been assumed that the sodium content of the body determines the rate of urinary sodium excretion, and a mass balance has been used to obtain differential equations that describe the dynamics of sodium stores. Both first- and second-order models are considered, and their predictions for both steady states and transients are compared critically with observations from the literature, using data from human studies whenever possible. The results indicate that a relatively simple proportional feedback controller describes most available data well; however, gaps in the available information are identified, and opportunities for future experimental investigation are described.
Glucose transport and metabolism in the brain
Authors: Robinson P. J. , Rapoport S. I.
Published: December 2017

A model is proposed for the uptake and metabolism of cold and radiotracer glucose that takes into account the concentration profiles of the cold and tracer glucose as they pass through the capillary bed of the brain. The model incorporates capillary blood flow, nonlinear transport between blood and brain, and Michaelis-Menten kinetics for incorporation of glucose into the brain metabolic pool. Analytical equations are derived for the conditions of normoglycemia and hypoglycemia. In normoglycemia, cold glucose uptake is determined solely by metabolic demand and is relatively independent of fluctuations in plasma glucose levels. At lower glucose levels, transport of glucose across the blood-brain barrier becomes a progressively more important factor in determining uptake. Uptake of radiotracer glucose depends primarily on transport parameters. Functional heterogeneity of the capillary bed is considered both in relation to glucose uptake and parameter estimation.
Brain temperature changes coupled to sleep states persist during interleukin 1-enhanced sleep
Authors: Walter J. , Davenne D. , Shoham S. , Dinarello C. A. , Krueger J. M.
Published: December 2017

The effects of human interleukin 1 (IL 1) on the architecture of rabbit sleep-wake cycles and brain temperature (Tbr) changes coupled to states of vigilance were examined. Cerebral intraventricular infusion of IL 1 induced increased slow-wave sleep (SWS), increased electroencephalographic slow-wave (0.5-4 Hz) amplitudes, and fever. Heat-inactivated IL 1 failed to elicit these responses. IL 1 also significantly inhibited rapid-eye-movement (REM) sleep; however, inactivated IL 1 also reduced REM sleep; thus some of the IL 1-induced REM reduction may be related to the infusion process. The duration and number of sleep cycles (REM-to-REM interval) were unaffected by IL 1. Similarly, Tbr changes that normally occur during the transition from one arousal state to another remained unchanged after IL 1 infusion, even though rabbits were simultaneously febrile. We conclude that IL 1 selectively enhances SWS while leaving sleep cycles and Tbr changes coupled to states of vigilance undisturbed.
Mechanisms of adrenergic control of blood pressure in developing rats
Authors: Mills E. , Smith P. G.
Published: December 2017

The rat is a species in which the sympathetic nervous system (SNS) is highly immature at birth. Blood pressure was measured directly in anesthetized preparations starting on the first postnatal day (days 1, 5, 9, 20, 40, 55, and 85), and pharmacological tests were used to evaluate the functional development of the vasomotor nerves (maximum pressor response to tyramine), the sensitivity of the vasculature to direct stimulation of alpha 1-adrenoceptors (maximum and 50% effective dose of methoxamine pressor response), and relative magnitude of the SNS contribution to resting blood pressure (hypotensive response to ganglionic blockade divided by resting blood pressure). The SNS contribution was not significant on postnatal day 1, but the relative magnitude was comparable to the adult by the end of the first postnatal week. During week 1 the vasomotor nerves were functionally immature (tyramine response was 48% of mature value on day 5), and the vasculature was supersensitive to alpha 1-adrenoceptor stimulation (154% of mature value). Conversely, in postnatal weeks 2 and 3, when the developing SNS is known to be hyperactive, the vasculature was subsensitive to noradrenergic stimulation (60-70% of adult). The net effect was to attenuate the SNS contribution to resting blood pressure during this period (55% of adult value). We conclude that there is an inverse relation between the level of tonic SNS activity and vascular sensitivity to noradrenergic stimulation in the developing rat. Supersensitivity may be critical for cardiovascular adjustments to asphyxia perinatally when the vasomotor nerves are functionally immature; subsensitivity may act homeostatically to prevent hypertension during the developmental period when SNS is hyperactive.
Effects of atriopeptin infusion versus effects of left atrial stretch in awake dogs
Authors: Goetz K. L. , Wang B. C. , Geer P. G. , Sundet W. D. , Needleman P.
Published: December 2017

We infused synthetic atriopeptin III intravenously into 10 conscious dogs while monitoring renal function and systemic hemodynamics. The results obtained from these infusion experiments were compared with results from other experiments in which left atrial distension was performed in the same dogs. Both atriopeptin infusion and left atrial distension caused significant increases in urine flow, sodium excretion, potassium excretion, and free water reabsorption and a significant decrease in renal blood flow. On the other hand, the pattern of systemic hemodynamic responses to atriopeptin infusion were quite different from the hemodynamic responses elicited by left atrial distension. However, there was a striking concordance between the renal effects of atriopeptin and those of left atrial distension. We therefore hypothesize that the renal response to left atrial distension in the conscious dog is mediated largely by the release of natriuretic peptides from the atria.
Studies on avian erythrocyte metabolism. XIV. Effect of CO2 and pH on P50 in the chicken
Authors: Isaacks R. , Goldman P. , Kim C.
Published: December 2017

The O2 affinity (P50) of erythrocyte suspensions from 18-day chick embryos, from 2-, 5-, 8-, and 14-day chicks, and from mature chickens decreased with increasing concentrations of either CO2 or H+, particularly at a pH near 7.4 and at 37 degrees C. A greater effect on delta P50's was observed from increasing H+ concentration from pH 8.0 to 6.8 in cell suspensions from 18-day embryos (28.8 Torr at 0% CO2) and adult chickens (55.1 Torr at 0% CO2) than from increases in CO2 concentration at any given pH. The Bohr effect (delta log P50/delta pH) in the absence of CO2 was -0.508 and -0.479 for cell suspensions from 18-day chick embryos and adult birds, respectively. The specific effect of CO2 on the Bohr effect, regardless of the CO2 concentration, indicates that the delta P50/0.1 pH is approximately 1.35 and 2.45 Torr for the embryo and adult chicken blood. These results indicate that increasing H+ and CO2 concentrations markedly affect the P50 of chicken blood and that even subtle changes in either could play a significant role physiologically in regulating blood P50 in birds.
Water and nonelectrolyte permeability in brain synaptosomes isolated from normal and uremic rats
Authors: Verkman A. S. , Fraser C. L.
Published: December 2017

Water and nonelectrolyte permeabilities of synaptosomes isolated from the brain of normal and uremic rats were measured by stopped-flow light scattering. Intensity of scattered light (550 nm) increased linearly with decreasing synaptosome size in the range of normal size to 30% of normal size. In response to a 250-mM inwardly directed gradient of an impermeant solute (mannitol or sucrose), there was a 100- to 500-ms time course of increased light scattering resulting from osmotic water efflux. In response to an inwardly directed urea gradient, light scattering first increased (water efflux) and then decreased (urea influx) over a 2- to 10-s time course. Based on an average synaptosome surface-to-volume ratio of 86,000 cm-1, determined by electron microscopy, the permeability coefficient for osmotic water transport (Pf) is 4.5 X 10(-3) cm/s and for urea transport (Purea) is 1.5 X 10(-6) cm/s (23 degrees C); temperature-dependent studies gave an activation energy for Pf of 18 (greater than 16 degrees C) and 3 kcal/mol (less than 16 degrees C) and for Purea of 9.8 kcal/mol (10-55 degrees C). Osmotic water and urea transport were not inhibited by 2 mM p-chloromercuribenzene sulfonate, 120 microM phloretin, and 10 microM phenylurea or by exposure to high-energy radiation (0-10 Mrad). Diffusional water permeability coefficient is approximately 4 X 10(-4) cm/s based on the time course of light scattering after mixture of synaptosomes in D2O buffer with isosmotic H2O buffer. Water and urea transport properties of synaptosomes isolated from uremic rats were not significantly different from those of normal rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Endogenous hormones and regulation of uterine blood flow during pregnancy
Authors: Caton D. , Kalra P. S.
Published: December 2017

Fourteen pregnant sheep were prepared for measurements of blood flow through a major uterine artery (UBF) and of arterial concentrations of estrone, estradiol, and progestagen. Five of the animals were ovariectomized. Measurements were made daily (n = 12) or every 4 h for 24 h (n = 4). Statistically significant (P less than 0.01) correlation coefficients were detected between UBF and hormone, either alone or in combination; the closest and most consistent associations were those in which estrogen and progestagen concentrations were summed or multiplied. Ewes with higher hormonal concentrations were those that had the higher rates of UBF. Correlation coefficients were statistically significant more often among ovariectomized animals. No associations were detected within one animal that delivered a growth-retarded fetus nor from any of the 24-h data. Estrogens and progestagen accounted for as much as 25% of the daily variation of UBF among and within sheep during the last half of pregnancy.
Resetting of mammalian respiratory rhythm: existence of a phase singularity
Authors: Paydarfar D. , Eldridge F. L. , Kiley J. P.
Published: December 2017

The purpose of this study was to use topological methods of analysis to determine if a phase singularity exists for the neural respiratory oscillator. We studied resetting behavior of central respiratory rhythm, measured as phrenic nerve activity, by using brief stimulations of the superior laryngeal nerve in anesthetized paralyzed adult cats. The strength and timing of stimuli were varied, and the times of onset of subsequent breaths were measured. Two distinct types of phase resetting were identified: type 1 resetting for weak stimuli and type 0 resetting for strong stimuli. With stimuli of intermediate strength, we obtained a series of phase-resetting curves that defined a helicoid-resetting surface having a phase singularity near the transition between late expiration and early inspiration. In this domain resumption of breathing occurred at highly variable resetting times. The mammalian respiratory oscillator thus has qualitative characteristics of response to brief stimuli that are similar to those of other biological oscillators.
Effects of human atrial natriuretic peptide on renal function and vasopressin release
Authors: Kimura T. , Abe K. , Shoji M. , Tsunoda K. , Matsui K. , Ota K. , Inoue M. , Yasujima M. , Yoshinaga K.
Published: December 2017

To assess the effects of atrial natriuretic peptide (ANP) on the renal function, cardiovascular system, renin-angiotensin-aldosterone system, and vasopressin release, synthetic human ANP (alpha-hANP) was administered at a dose of 0.08 microgram X kg-1 X min-1 iv for 40 min into anesthetized dogs (n = 6). In the control study (n = 6), saline alone was infused. alpha-hANP brought about a significant increase in renal plasma flow, urinary Na and K output, urine flow, and osmolar clearance and a significant decrease in urinary osmolality, free water clearance, and filtration fraction (FF), with no changes in glomerular filtration rate. Plasma Na concentrations and osmolality did not change significantly, but plasma K concentrations fell progressively. Mean arterial blood pressure decreased without any changes in heart rate. Plasma renin activity (PRA), plasma aldosterone concentrations (PAC), and plasma vasopressin concentrations did not rise, but rather PRA and PAC tended to fall during alpha-hANP infusion. In the control study, there were no changes in these parameters except a progressive fall in FF and plasma K concentrations. These results indicate that the alpha-hANP-induced increase in renal blood flow plays an important role in producing natriuresis, but vasopressin may not be involved in the process of diuresis.
Interaction of bradykinin and prostaglandin E1 on cardiac pressor reflex and sympathetic afferents
Authors: Nerdrum T. , Baker D. G. , Coleridge H. M. , Coleridge J. C.
Published: December 2017

Bradykinin applied to the epicardium stimulates cardiac sympathetic afferents and evokes a reflex increase in arterial blood pressure. In anesthetized cats we examined the potentiation of these effects by prostaglandin E1 (PGE1) applied to the ventricular epicardium. We recorded cardiac afferent impulses from the second to the fifth left thoracic sympathetic rami. PGE1 (0.1 microgram/ml) alone had little effect on blood pressure, but it significantly increased the pressor response to bradykinin, and it reduced or abolished tachyphylaxis to repeated applications of bradykinin. Both mechanosensitive and chemosensitive sympathetic cardiac afferents were stimulated by bradykinin. Indomethacin (intravenous) caused a small reduction in the afferent response to bradykinin. Epicardial application of PGE1 significantly increased the response (magnitude and duration) of chemosensitive endings to bradykinin but not that of mechanosensitive endings; however, PGE1 abolished the tachyphylaxis of both chemosensitive and mechanosensitive endings to repeated applications of bradykinin. Because both bradykinin and prostaglandins are released in the ischemic myocardium, their interactive effect on cardiac sympathetic afferents could play a part in the sensory and reflex responses to myocardial ischemia.
Effect of fasting interval on CCK-8 suppression of food intake in the baboon
Authors: Stein L. J. , Porte D. , Figlewicz D. P. , Woods S. C.
Published: December 2017

Baboons were infused intravenously for 5 min with the octapeptide of cholecystokinin (CCK-8) after either a 16.5- or 3.5-h fast. After a 3.5-h fast, food intake was significantly suppressed over the ensuing 30 min by 2 micrograms/kg of CCK-8 (-156 +/- 34 kcal compared with control days, P less than 0.02) and by 4 micrograms/kg of CCK-8 (-257 +/- 31 kcal, P less than 0.01). In contrast, CCK-8 had no reliable effect on food intake after the same baboons had been fasted for 16.5 h (2 micrograms/kg: -93 +/- 40 kcal, P greater than 0.05; 4 micrograms/kg: -30 +/- 82 kcal, P greater than 0.05). There was no reliable effect of 1 microgram/kg of CCK-8 on food intake at either deprivation interval. CCK-8 infusions resulted in a small increase of fasting plasma immunoreactive insulin (IRI); this effect was not related to either dose or deprivation length. Postprandial IRI and glucose concentrations were significantly suppressed by CCK-8 independently of its effect on food intake. Thus, after a 16.5-h fast, 4 micrograms/kg of CCK-8 decreased postprandial IRI from 145 +/- 65 to 29 +/- 4 microU/ml (P less than 0.01) and glucose from 101 +/- 5 to 80 +/- 3 mg/dl (P less than 0.02), despite no concomitant effect on food intake. Similar suppression of plasma IRI and glucose were observed after infusions of 1 and 2 micrograms/kg in 16.5-h-fasted animals. All doses of CCK-8 (1, 2, and 4 micrograms/kg) suppressed postprandial IRI and glucose after a 3.5-h fast.(ABSTRACT TRUNCATED AT 250 WORDS)