bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein turnover in skeletal muscle of suckling rats
Authors: Davis T. A. , Fiorotto M. L. , Nguyen H. V. , Reeds P. J.
Published: December 2017

To determine the normal changes in protein turnover of skeletal muscle in vivo during the suckling period of rats, protein synthesis was measured in soleus, plantaris, anterior tibialis, and extensor digitorum longus (EDL) muscles of 1- to 28-day-old rats using a flooding dose of L-[4-3H]phenylalanine. Protein mass of hind-limb muscles increased nearly 100-fold, and RNA increased approximately 20-fold between 1 and 28 days of age. The total amount of protein synthesized per day increased 34-fold. Fractional protein synthesis rates (Ks) decreased two- to threefold between 1 and 28 days postpartum as a result of a decrease in protein synthetic capacity (RNA/protein). Protein synthetic efficiency (total protein synthesized/RNA) increased during this period. Ks were similar among the four muscles at 1-10 days. At 16 days, Ks increased in soleus and plantaris as a result of increases in protein synthetic efficiency; Ks did not increase in anterior tibialis and EDL. These data suggest that, during the suckling period, protein synthetic capacity in skeletal muscles of rats declines, while protein synthetic efficiency increases. The increase in translational efficiency occurred earlier in weight-bearing muscles (soleus, plantaris) than in non-weight-bearing muscles (anterior tibialis and EDL) and was associated with the appearance of mobility.
Renal potassium transport: morphological and functional adaptations
Authors: Stanton B. A.
Published: December 2017

Maintenance of K+ homeostasis in mammals and amphibians depends primarily on the kidneys which excrete 95% of K+ ingested in the diet. The amount of K+ in the urine is determined by the rate of K+ secretion or absorption by the distal tubule and the collecting duct. When K+ intake is increased, K+ secretion rises. The mechanisms of K+ secretion by the distal tubule and collecting duct are so efficient that K+ intake can increase 20-fold with little or no increase in body K+ content or in plasma K+ concentration. Elevated K+ secretion by the distal tubule and collecting duct occurs in part because of an increase in the quantity of Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) and amplification of the basolateral membrane of principal cells. When dietary K+ intake is reduced, urinary K+ excretion falls, because K+ secretory mechanisms are suppressed and K+ absorptive mechanisms, residing in the distal tubule and collecting duct, are activated. Because a low-K+ diet is associated with hypertrophy of intercalated cells, it has been suggested that this cell type absorbs K+, possibly by an H+-K+-ATPase. In this review, I discuss the functional and morphological evidence that supports the view that principal cells secrete K+ and that intercalated cells absorb K+. In addition, some of the hormones and factors that are responsible for these changes in cell structure and function are discussed.
Effect of atriopeptin on blood flow to cerebrum and choroid plexus
Authors: Schalk K. A. , Williams J. L. , Heistad D. D.
Published: December 2017

The goal of this study was to determine whether atriopeptin alters blood flow to cerebrum and choroid plexus. In anesthetized rabbits, blood flow (microspheres) to cerebrum and choroid plexus under control conditions was 36 +/- 3 (mean +/- SE) and 573 +/- 78 ml.min-1.100 g-1, respectively. Infusion of atriopeptin (75, 225, 1,150 ng.kg-1.min-1 iv) increased blood flow to choroid plexus by 22 +/- 11, 53 +/- 26, and 51 +/- 13%, respectively. In contrast, blood flow to cerebrum was not altered by atriopeptin, presumably because the blood-brain barrier prevented access to cerebral vascular smooth muscle. Because a major role of atriopeptin may be to modulate responses to angiotensin II, we examined effects of atriopeptin on vasoconstrictor responses to angiotensin II in the choroid plexus. Angiotensin II was infused in the presence or absence of atriopeptin (300 ng.kg-1.min-1 iv). Angiotensin II (100 ng.kg-1.min-1 iv) decreased blood flow to choroid plexus by 49 +/- 12% and by 47 +/- 14% during simultaneous infusion of atriopeptin. In summary, atriopeptin 1) increases blood flow to choroid plexus, but not cerebrum, and 2) does not appear to attenuate vasoconstrictor effects of angiotensin II in the choroid plexus.
Effects of corticotropin-releasing factor on energy balance in rats are sex dependent
Authors: Rivest S. , Deshaies Y. , Richard D.
Published: December 2017

The purpose of this study was to investigate the effects of a chronic intracerebroventricular administration of corticotropin-releasing factor (CRF) on energy balance of male and female rats. One week after their delivery to the laboratory, both male and female rats were divided into two groups. One group in each sex was treated with human/rat CRF, while another group was infused with the vehicle. Chronic administration of CRF was accomplished by means of miniosmotic pumps connected to a cannula that was stereotaxically directed into the third ventricle. Food intake and body weight were measured each day during the study. After 14 days of treatment, the rats were killed by decapitation. Energy, fat, and protein contents of the carcasses were quantified. Serum testosterone and estradiol were assayed in males and females, respectively. Administration of CRF significantly reduced body weight gain and food intake in male rats. No significant difference in those variables was observed between female rats treated with CRF and their controls infused with saline. Similarly, metabolizable energy intake and body energy gain were reduced in male rats infused with CRF, whereas no difference was observed between female animals treated with CRF and those infused with saline. In male rats, body fat and body protein contents were lower in CRF-treated than in saline-infused rats. In female rats, CRF did not affect body composition. Serum testosterone in male rats and serum estradiol in female animals were reduced after chronic infusion of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)
Different hemodynamic effects of atrial natriuretic factor and nitroglycerin in rats with congestive heart failure
Authors: Chien Y. W. , Trippodo N. C. , Frohlich E. D.
Published: December 2017

Atrial natriuretic factor (ANF) decreases cardiac filling pressure, suggesting that diminished venous return is an important mechanism for the associated reduction in cardiac output. To determine whether ANF reduces cardiac preload through venodilation in congestive heart failure (CHF), we compared the hemodynamic effects of ANF-(99-126) with those of the venodilator nitroglycerin in conscious rats with CHF induced by coronary artery ligation previously. Depending on the extent of myocardial infarction, rats were subdivided into two groups: 1) mild or 2) severe CHF. Incremental intravenous infusions of ANF (0.1, 0.25, 0.5 micrograms.kg-1.min-1) or nitroglycerin (2, 5, 10 micrograms.kg-1.min-1) were administered for 20 min at each dose. Both agents reduced cardiac filling pressures. There was no change in cardiac output or arterial pressure at any dose of ANF in rats with severe CHF, but cardiac output decreased at higher ANF doses in rats with mild CHF. In contrast, nitroglycerin produced no change in cardiac output at any dose in either CHF group, although it decreased arterial pressure at the higher doses in rats with severe CHF. ANF increased whereas nitroglycerin decreased hematocrit in both CHF groups. The ANF-induced hematocrit increase also occurred in those rats with vesicovenous shunts designed to prevent volume contraction induced by diuresis. These data suggest that ANF and nitroglycerin decreased cardiac filling pressure through different hemodynamic mechanisms. The known venodilator action of nitroglycerin was associated with decreased hematocrit, suggesting enhanced transcapillary fluid migration. However, ANF produced an opposite effect on fluid migration as demonstrated by an increased hematocrit, suggesting a mechanism other than venodilation must be operative in reducing cardiac filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of spinal cord transection on sympathetic discharge in decerebrate-unanesthetized cats
Authors: Weaver L. C. , Stein R. D.
Published: December 2017

Previous experiments in our laboratory have shown that discharge of splenic, mesenteric, and splanchnic nerves is well maintained after spinal cord transection in chloralose-anesthetized cats (8, 9, 11). The primary purpose of this investigation was to determine if maintained sympathetic discharge could be observed after spinal transection in the absence of chloralose anesthesia. In cats anesthetized with alphaxalone-alphadolone, changes in splanchnic discharge, blood pressure, and heart rate caused by decerebration and removal of the forebrain were observed. This procedure decreased blood pressure, increased heart rate, and had no immediate effect on sympathetic discharge or its rhythm (assessed by power density spectral analysis). One hour after decerebration and termination of anesthesia, splanchnic discharge had increased by approximately 36%. Next, effects of spinal cord transection on discharge of splanchnic, mesenteric, and renal nerves were observed in the decerebrate-unanesthetized cats. Splanchnic discharge decreased by 50%, mesenteric nerve discharge was unchanged, and renal nerve discharge decreased by 97%. Therefore, splanchnic nerve discharge was not as well maintained in decerebrate-unanesthetized cats as it had been in chloralose-anesthetized animals, and the remaining splanchnic discharge appeared to affect mesenteric nerves preferentially. Finally, spectral analysis of the splanchnic discharge demonstrated that before cord transection, most of the signal was in the 0- to 6-Hz frequency range, whereas after transection the proportion of signal in this frequency range was significantly reduced and the proportion in higher frequencies (7-25 Hz) was significantly increased. This loss of low-frequency rhythmicity is consistent with findings in our previous studies in chloralose-anesthetized cats.
Fetal swallowing: response to systemic hypotension
Authors: Ross M. G. , Sherman D. J. , Ervin M. G. , Day L. , Humme J.
Published: December 2017

The fetal swallowing and endocrine responses to systemic hypotension were studied in five chronically instrumented ovine fetuses (125 +/- 2 days). Fetuses were prepared with bipolar electrodes inserted in the thyrohyoid muscle, nuchal esophagus, and thoracic esophagus, a flow probe surrounding the thoracic esophagus, and arterial and venous catheters. In response to an intravenous infusion of sodium nitroprusside, fetal mean arterial blood pressure decreased from 50.8 +/- 3.6 to 41.7 +/- 3.8 mmHg. Fetal plasma renin activity (5.0 +/- 1.4-25.1 +/- 10.3 ng.ml-1.h-1) and arginine vasopressin (5.6 +/- 4.5-26.3 +/- 21.0 pg/ml) increased, while fetal swallowing electromyogram activity (7.3 +/- 1.1-1.9 +/- 0.3 swallows/10 min) and esophageal flow (5.5 +/- 3.1-1.2 +/- 0.9 ml/10 min) significantly decreased during the nitroprusside infusion. These results indicate a suppression of fetal swallowing in response to systemic hypotension despite stimulation of the renin-angiotensin system.
Sympathetic modulation of cholinergic transmission in cat vesical ganglia is mediated by alpha 1- and alpha 2-adrenoceptors
Authors: Keast J. R. , Kawatani M. , De Groat W. C.
Published: December 2017

Modulation of transmission in cat vesical ganglia by exogenous catecholamines or short periods of hypogastric nerve stimulation (HGS) was examined in vivo. HGS (30 Hz, 30 V, 10- to 20-s train) initially caused inhibition of ganglionic transmission, followed by a period of facilitation. The inhibition could be evoked by lower stimulus intensities than the facilitation. The biphasic effect was mimicked by norepinephrine (2-10 micrograms) injected into the inferior mesenteric artery, whereas phenylephrine (5-10 micrograms) usually caused only facilitation. The administration of specific adrenoceptor antagonists showed that the inhibitory responses were mediated by alpha 2-receptors and the facilitatory responses by alpha 1-receptors. The effects of HGS and norepinephrine were also tested on pelvic nerve-evoked bladder contractions. Both caused a brief reduction in contraction amplitude which, for the HGS effect, was mediated mainly by alpha 2-receptors. Noradrenergic inhibition of bladder contractions was mediated by both alpha 2- and beta-adrenoceptors. These studies have shown that sympathetic modulation of ganglionic transmission in the bladder can be either inhibitory or facilitatory, each mediated by a specific receptor type. These two actions may be important during different stages of bladder storage or voiding.
AVP and dDAVP in rabbit cortical collecting tubule: a comparative time-course study
Authors: Leite M. , Suki W. N.
Published: December 2017

The V2-selective analogue of arginine vasopressin (AVP), dDAVP, has been used to distinguish between the effects of V1- and V2-receptor activation by AVP in different cell types of the kidney. Based on studies showing different effects of AVP and dDAVP on prostaglandin secretion, and also on cytosolic Ca2+, we designed a comparative time-course study of both agonists on rabbit microdissected cortical collecting tubules (CCT) microperfused in vitro at 38 degrees C. Plots of the effects of AVP (10 microU/ml or 2.2 x 10(-11) M and 100 microU/ml or 2.2 x 10(-10) M) and dDAVP (10 microU/ml or 0.8 x 10(-11) M) on osmotic water permeability (Pf) at comparable antidiuretic activities, revealed an increase of Pf that was maintained for as long as 170 min of hormone exposure. Also the magnitude of increase in Pf and the time required to achieve the more sustained phase of response were comparable, with no significant difference between the two agonists. These results clearly demonstrate a stable response of rabbit CCT to AVP and dDAVP at physiological temperature, and they reveal no evidence for a difference between the native hormone AVP and its V2 selective analogue on the net hydrosmotic response of the CCT.
Diazepam inhibits stimulating effect of cooling preoptic area on antibody production
Authors: Banet M. , Brandt S.
Published: December 2017

To clarify the mechanism of the stimulating effect of fever on the primary antibody response, rats were immunized with sheep erythrocytes, and a fever-like response was induced by cooling the preoptic area for five days. Diazepam, 0.5 mg/kg, given daily during the cooling time, did not affect the normal antibody response of the control animals nor did it prevent the rise in body temperature elicited by cooling the preoptic area but it did, nevertheless, strongly reduce the stimulating effect of this procedure on antibody production. A smaller reduction of this effect was also seen in adrenalectomized rats in which a physiological and stable plasma level of corticosterone was maintained. Because diazepam suppresses some sympathetic and endocrine responses to stress, these data suggest that the effect of cooling the preoptic area on the primary antibody response, and, by inference, that of fever, is to a large extent mediated by the adrenal and other stress response or responses to the cold stimulus. The results do not, however, exclude the possibility of an additional, direct effect of the elevated body temperature on immunocompetent cells.
Generation of vasoactive substances in trout and rat plasma by trypsin and kallikrein
Authors: Lipke D. W. , Meisheri K. D. , Olson K. R.
Published: December 2017

In the preceding study we demonstrated kallikrein-like enzymatic activity in trout tissues and showed that kallikrein incubated with trout plasma (T60K) produces a vasopressor substance(s). The present study further examines the effects of T60K in fish and mammals in vitro and in vivo. T60K produced a dose-dependent pressor response in both trout and rats, whereas kallikrein-activated rat plasma (R60K) was pressor in trout and depressor in rats. Captopril did not affect the response of rats to T60K or R60K. Phenoxybenzamine attenuated the T60K response in trout but not in rats, thus T60K effects in trout are partially mediated through catecholamines. Blockade of angiotensin II (ANG II) receptors in rats with [Sar1,Ala8]-ANG II abolished the pressor effects of T60K. T60K produced dose-dependent contractions in isolated trout and rabbit arteries; ANG II was ineffective in trout arteries. T60K-contracted trout arteries were relaxed by atrial natriuretic peptide and forskolin, whereas diltiazem and sodium nitroprusside were without effect. [Sar1,Ala8]ANG II inhibited T60K-induced contractions of rabbit arteries and relaxed rings previously contracted with T60K. The active component of T60K has a molecular weight less than 10,000, is heat stable, and is inactivated by peptidases. It is immunologically different than mammalian angiotensins but binds to and displaces radiolabeled ANG II from ANG II receptors. These results suggest that kallikrein forms a vasoactive substance(s) in trout plasma that is neither bradykinin nor ANG II but is similar to the latter in its pharmacological effects.
Somnogenic, pyrogenic, and hematologic effects of experimental pasteurellosis in rabbits
Authors: Toth L. A. , Krueger J. M.
Published: December 2017

Previous work has demonstrated that intravenous inoculation of rabbits with various microorganisms induces complex time-dependent alterations in sleep as well as other pathophysiological effects typically associated with infectious disease. To evaluate the effects of bacterial challenge that more closely resembles naturally developing disease, we inoculated rabbits with Pasteurella multocida, a common pathogen of this species, using routes of administration that mimic normal routes of exposure. Biphasic sleep alterations characterized initially by enhanced slow-wave sleep and later by decreased slow-wave sleep occurred after intravenous, intramuscular, subcutaneous, or intranasal inoculation. Rapid-eye-movement sleep was inhibited for most of the 48-h period after inoculation. Inoculation by all four routes also induced fever and qualitatively similar hematologic changes. However, the magnitude and specific temporal patterns of both somnogenic changes and other pathophysiological effects varied with the route of inoculation.
Ultradian adrenocortical and circulatory oscillations in conscious dogs
Authors: Benton L. A. , Yates F. E.
Published: December 2017

We examined adrenal blood flow, cortisol secretion rate, concentration of cortisol in adrenal venous blood, mean arterial blood pressure, and heart rate in unrestrained conscious dogs, sampling at 15-20 s, 5 min, or 10 min during experiments lasting from 30 min to 8 h. Time history analysis designed for short, noisy time series detected three significant ultradian oscillatory periods: approximately 3, 6, and 90 min. Circulatory variables (systemic mean arterial pressure, heart rate, and adrenal blood flow) showed all three. Cortisol secretion rate showed the 3- and 90-min oscillations but not the 6-min oscillation. Adrenal glucocorticoid secretion rate and adrenal blood flow were not strongly coupled. However, at one extreme of blood flow (close to zero) and at the opposite extreme (very high blood flow stimulated by adrenocorticotropic hormone) adrenal blood flow and cortisol secretion were tightly coupled. In the normal physiological range, the multiperiodic, rhythmic organization of circulatory variables and adrenal glucocorticoid function arises from independent or only weakly coupled oscillators, not necessarily harmonically related, manifesting near-periodicity with wobble and intermittency.
Central nervous system cardiovascular actions of CRF in sinoaortic-denervated rats
Authors: Overton J. M. , Davis-Gorman G. , Fisher L. A.
Published: December 2017

Studies were performed in unrestrained conscious Sprague-Dawley rats to examine the central nervous system (CNS) mechanism by which corticotropin-releasing factor (CRF) produces simultaneous elevations of arterial pressure and heart rate. To test the hypothesis that CRF inhibits ongoing impulse transmission through and/or transmitter release from the CNS terminations of baroreceptor afferents, the cardiovascular effects of intracerebroventricular administration of CRF were compared in rats subjected to prior sham surgery (Sham) or sinoaortic denervation (SAD). Resting levels of arterial pressure and heart rate were elevated after SAD. In addition, SAD resulted in greater chronotropic sympathetic tone and reduced chronotropic parasympathetic tone as assessed by intravenous injections of atropine methyl nitrate and DL-propranolol. Intracerebroventricular administration of CRF in both surgical groups elicited significant increases in arterial pressure and heart rate, although a tendency for reduced tachycardic responses after SAD was apparent. Pretreatment with atropine or propranolol revealed that both the parasympathetic and sympathetic nervous systems contribute to CRF-induced heart rate responses in both surgical groups. These results suggest that ongoing baroreceptor afferent transmission is not requisite for the expression of CRF-induced cardiovascular changes. Thus it is unlikely that CRF elevates arterial pressure and heart rate through an exclusive action at the CNS terminations of baroreceptor sensory fibers.
Response of prolactin to hemorrhage is similar to that of adrenocorticotropin in swine
Authors: Carlson D. E. , Klemcke H. G. , Gann D. S.
Published: December 2017

Prolactin (PRL) responds to several stimuli that elicit release of adrenocorticotropin (ACTH), but does not increase in response to hemorrhage in fetal animals. To determine whether PRL increases after hemorrhage in older animals, 11 immature female swine were prepared chronically under halothane and conditioned behaviorally to lie in a sling. They were bled 14 ml/kg over 5 min. PRL, ACTH, cortisol (F), lysine vasopressin (LVP), and pressure renin activity (PRA) were measured by radioimmunoassay. Epinephrine (EPI) and norepinephrine (NE) were separated by high-performance liquid chromatography. Arterial PRL increased at 0.75 and 1 h (P less than 0.01) and paralleled ACTH and F that peaked at 0.75 h (P less than 0.05 and P less than 0.01, respectively). All three hormones recovered significantly by 4 h. In contrast, PRA and LVP peaked transiently at 0.25 h after hemorrhage and recovered by 1.5 h (P less than 0.05, in each case). EPI and NE did not change significantly. In individual pigs, ACTH and F each showed correlations (Spearman) with PRL that were positive in 10 pigs and significant in six and five pigs, respectively. The pig with the smallest ACTH change (8.4 pg/ml peak) showed no increase in PRL. Peaks in PRL were simultaneous with (five pigs) or delayed by 15 min (four pigs) or 30 min (one pig) from peaks in ACTH. Significant correlations of PRL with PRA and with LVP occurred in only two pigs and in one pig, respectively. A common pathway may contribute to other independent mechanisms controlling the release of ACTH and PRL after hemorrhage.
Ascending collaterals of medullary barosensitive neurons and C1 cells in rats
Authors: Haselton J. R. , Guyenet P. G.
Published: December 2017

Triple-label experiments were conducted in rats to determine whether reticulospinal C1 adrenergic neurons of rostral ventrolateral medulla (RVLM) also innervate dorsolateral pons (LPBN/KF), mesencephalic central gray area (CG), and hypothalamus (LH). Ten percent of RVLM neurons that project to LPBN/KF were immunoreactive for tyrosine hydroxylase (TH), and 50% of those projecting to either pariaqueductal gray (PAG) or LH were TH immunoreactive. A large proportion of RVLM TH-immunoreactive neurons that were retrogradely labeled from either LPBN/KF or PAG (65.5 and 28.5%, respectively) were retrogradely labeled from the spinal cord as well. A smaller fraction of RVLM TH-immunoreactive neurons that were labeled from LH were also labeled from the spinal cord (13.1%). The vast majority of the cohaterized RVLM neurons were TH immunoreactive (LPBN/KF 50%; PAG 82%; LH 84%), and the remaining ones may be nonadrenergic neurons. Antidromic (AD) mapping techniques were also used to determine if RVLM reticulospinal barosensitive neurons (putative vasomotor sympathoexcitatory cells, total sample of 106) send axonal collaterals to the supramedullary areas investigated anatomically. Twenty percent of the cells sampled (n = 21) were also AD activated from 1 of 20 supramedullary sites. The combined approaches support the following conclusions: 1) RVLM barosensitive neurons include phenotypically adrenergic cells, and 2) RVLM barosensitive cells do not represent an output pathway solely dedicated to providing an excitatory drive to sympathetic preganglionic neurons.
Effects of pyrogen administration on temperature regulation in exercising rats
Authors: Tanaka H. , Kanosue K. , Yanase M. , Nakayama T.
Published: December 2017

To study the mechanism of rise in body temperature during exercise, endogenous pyrogen was administered to exercising rats. At rest and at a neutral ambient temperature (Ta) of 24 degrees C, intravenous injection of recombinant human interleukin 1 (IL-1, 40 micrograms/kg) produced a 0.5 degree C rise in rectal temperature (Tre) from 37.4 degrees C. At Ta of 34 degrees C, at which Tre was 38.6 degrees C, Tre rise in response to IL-1 was only 0.2 degree C greater than when saline was used. In the first series of exercise experiments, rats ran on a treadmill after IL-1 or saline injection at two different work intensities (estimated at 40 and 60% of maximal oxygen uptake) at 24 degrees C Ta. At either work intensity, the magnitude of Tre rise after IL-1 injection was approximately 0.5 degree C higher than after saline injection. Threshold Tre for tail vasodilation increased when IL-1 was injected. The difference in the threshold Tre between the IL-1 and saline conditions was 0.5 degree C at either work intensity. Evaporative heat loss was also suppressed and metabolic heat production facilitated when IL-1 was injected. In a second series of experiments, IL-1 was injected after Tre reached a steady state (38.5 degrees C) during exercise. After IL-1 injection Tre increased another 0.5 degrees C, but after saline injection Tre did not change. These results suggest that body temperature rise during exercise is not induced merely by an insufficient capability of dissipating heat and that the thermoregulatory set point is reset during exercise.
Regional hemodynamic effects of endothelin-2 and sarafotoxin-S6b in conscious rats
Authors: Gardiner S. M. , Compton A. M. , Bennett T.
Published: December 2017

Regional hemodynamic responses to bolus doses (4 and 40 pmol) and 60-min infusions (12 and 120 pmol/h) of endothelin-2 (ET-2) and sarafotoxin-S6b (S6b) were measured in conscious Long-Evans and Brattleboro rats chronically instrumented with pulsed Doppler flow probes. In both strains of rat the two bolus doses of ET-2 and S6b peptides caused an initial fall in mean blood pressure (MBP). At the higher dose S6b caused a greater fall in MBP than ET-2. In Long-Evans rats the fall in MBP after S6b was associated with renal, mesenteric, and hindquarters vasodilatations; in Brattleboro rats there was no renal or mesenteric vasodilatation with S6b. The high dose of ET-2 caused early mesenteric vasoconstriction in both strains. After the initial fall in MBP there were dose-dependent increases in MBP together with renal and mesenteric vasoconstrictions. These effects were generally greater after S6b than after ET-2 and no less marked in Brattleboro than in Long-Evans rats, indicating that release of endogenous vasopressin was not an indispensable component of the response. Infusions of the higher dose of ET-2 or S6b caused increases in MBP only, associated with renal, mesenteric, and hindquarters vasoconstrictions. The results indicate that S6b is a more potent stimulus than ET-2 of vasodilator mechanisms in vivo; despite this, S6b also exerts more marked vasoconstrictor effects than ET-2.
Phase-shifting the light-dark cycle resets the food-entrainable circadian pacemaker
Authors: Ottenweller J. E. , Tapp W. N. , Natelson B. H.
Published: December 2017

This experiment examined coupling between two circadian pacemakers, one entrained by light and the other by food. Rats were housed in running wheels: one-half on restricted feeding from 0900 to 1100 h whereas the others were free fed. After timed-fed rats developed bursts of running before 0900 h, all rats were given free access to food. A month later, the light-dark (LD) cycles for one-half the rats in each group were delayed by 6 h. After entrainment to the new LD cycles, all rats were probed with 96-h periods of food deprivation. During these probes, unshifted timed-fed rats ran more than their free-fed controls at 0600-1200 h, but delayed timed-fed rats ran more than their controls at 1200-1500 h, i.e., 6 h later than unshifted rats. Next, the unshifted rats were subjected to a 6-h advance in their LD cycle. One month later, all rats were again probed with food deprivation. Delayed timed-fed rats continued to run more at 1200-1500 h than their free-fed controls, but timed-fed and free-fed phase-advanced rats showed similar activity patterns after the phase advance. However, when activity patterns before these probes were subtracted, timed-fed advanced rats showed greater “responses” to food deprivation at 0001-0300 h than their free-fed controls, i.e., 6 h earlier than before the phase advance. Thus LD shifts delayed and advanced the running that was previously associated with food availability and reset the food-entrainable circadian pacemaker.
Effects of dietary protein intake on vasoactive hormones
Authors: Daniels B. S. , Hostetter T. H.
Published: December 2017

Vasoactive hormonal response to two levels of dietary protein intake was studied in seven healthy adult volunteers. The subjects were randomly placed on a 2-g.kg-1.day-1 (high) or 0.55-g.kg-1.day-1 (low) diet using a crossover design and were studied on the morning of the 5th day and again after 24 h of indomethacin treatment. Plasma renin activity (PRA), aldosterone, vasopressin, and urinary excretion of 6-ketoprostaglandin F1 alpha (PGF1 alpha) were significantly higher on the high-protein diet despite constancy of body weight, blood pressure, pulse, urinary sodium and potassium excretion, and plasma amino acid levels. After treatment with cyclooxygenase inhibitor indomethacin, 6-keto-PGF1 alpha excretion was equalized, but the elevated PRA and aldosterone levels persisted on the high-protein diet, suggesting that PRA and aldosterone elevations do not depend entirely on prostanoid release. We conclude that chronic augmentation of dietary protein intake is accompanied by alterations of vasoactive hormones, which persist for up to 10 h postprandially and are independent of elevated plasma amino acid levels. Such hormonal alterations may mediate some of the dietary protein-mediated changes in renal hemodynamics.
Enhanced atrial peptide natriuresis during angiotensin and aldosterone blockade in dogs
Authors: Bie P. , Wang B. C. , Leadley R. J. , Goetz K. L.
Published: December 2017

The hypothesis that the weak natriuretic effect elicited by modest amounts of atrial peptide is mediated via the inhibition of renin and aldosterone was evaluated in the conscious dog. The formation of angiotensin II (ANG II) and the effects of aldosterone (Aldo) were blocked acutely by enalaprilat and canrenoate, respectively. Infusion of alpha-human atrial natriuretic peptide (alpha-hANP) for 2 h at 25 ng.kg-1.min-1 increased plasma atrial peptide concentration 7- to 10-fold. In control experiments, i.e., experiments without ANG II-Aldo blockade, infusion of atrial peptide doubled urine volume (UV) from 0.21 +/- 0.01 to 0.43 +/- 0.09 ml/min and sodium excretion (UNaV) from 18 +/- 5 to 37 +/- 7 mueq/min; mean arterial blood pressure (AP) and atrial pressures decreased, whereas total peripheral resistance increased. The induction of ANG II-Aldo blockade elevated UNaV and UV 10- and 6-fold, respectively, and decreased AP. The subsequent 2-h infusion of atrial peptide elicited a further increase in UNaV (from 195 +/- 28 to 334 +/- 60 mueq/min); the hemodynamic changes were similar to those seen in the absence of ANG II-Aldo blockade, except that AP did not decrease significantly during the administration of atrial peptide. The data demonstrate that pharmacological inhibition of the effects of converting enzyme and Aldo does not impede the natriuretic response elicited by a 7- to 10-fold increase in circulating atrial peptide; in fact, the magnitude of the natriuresis is markedly enhanced during this blockade.
CNS injection of CCK in rats: effects on real and sham feeding and gastric emptying
Authors: Della-Fera M. A. , Coleman B. D. , Baile C. A.
Published: December 2017

Cholecystokinin (CCK) released from the intestine during feeding may have a physiological role in satiety. There is also evidence that activation of central CCK-containing pathways is involved in the control of feeding behavior. This study was carried out to determine whether CCK-8 administered into the lateral cerebral ventricles (lv) of rats suppresses both sham feeding (SF) and real feeding (RF). Rats with lv guides and gastric cannulas ate a liquid diet with cannulas open (SF) or closed (RF) after lv (0, 0.05, 0.5 micrograms) or intraperitoneal (ip) (0, 4 micrograms/kg) injection of CCK-8. Both RF and SF were significantly decreased by ip CCK-8. RF was also decreased in a dose-related manner after lv CCK-8, but SF was not affected by lv CCK-8. Decreased feeding after ip CCK-8 may be due in part to its suppression of gastric emptying rate (GER). To determine whether central nervous system (CNS) CCK might also be involved in the control of gastric function, GER was measured after lv (0, 0.05, 0.5 micrograms) or ip (0, 4 micrograms/kg) injection of CCK-8. GER was significantly decreased after ip CCK-8, but lv CCK-8 had no effect on GER. Although both CNS and peripheral CCK peptide systems may be involved in satiety, CNS CCK appears to depend on concurrent peripheral nutrient-related stimuli in eliciting satiety.
No effect of prostaglandin synthesis inhibition on muscle reflexes in fetal lambs
Authors: Walker D.
Published: December 2017

The effects of inhibiting prostaglandin (PG) synthesis on fetal breathing movements and on the amplitude of reflex contraction of the digastric muscle (five trials) or hindlimb semitendinosus muscle (seven trials) has been studied in six fetal lambs at 123-139 days gestation. Infusion of either indomethacin (100 mg) or acetaminophen (300 mg) in 30 ml saline over 30 min resulted in an increase in the amplitude and incidence of breathing movements for 3-18 h in the different trials, but there was no change in the mean amplitude of either reflex or in the normal variation of reflex amplitude with changes in electrocortical activity. It is concluded that PGs modulate fetal breathing movements by an action on the brain stem chemoreceptors but do not alter the excitability of neural pathways subserving some cranial and spinal reflexes.
Hemodynamic and behavioral effects of angiotensin II in conscious sheep
Authors: Breuhaus B. A. , Chimoskey J. E.
Published: December 2017

Intracerebroventricular (ivt) angiotensin II (ANG II) at 0.4, 2, 10, and 50 ng.kg-1.min-1 increased arterial pressure in conscious sheep in a dose-related manner (26 mmHg, P less than 0.05, at 50 ng.kg-1.min-1). Total peripheral resistance (TPR) and right atrial pressure also increased. Heart rate, stroke volume, and cardiac output did not change. Pressor responses to ivt ANG II were not caused by leakage of ANG II into the periphery, because plasma concentrations of ANG II did not change from control (31 +/- 7 pg/ml) at the highest dose of ANG II infused. In contrast, intravenous (iv) ANG II, 10 and 50 ng.kg-1.min-1, increased arterial pressure 29 and 47 mmHg, respectively (P less than 0.05), and decreased heart rate. ANG II, 10 ng.kg-1.min-1 iv, increased plasma ANG II levels from 36 +/- 6 to 354 +/- 69 pg/ml (P less than 0.05). Intracarotid (ic) ANG II, 10 ng.kg-1.min-1, increased arterial pressure 31 mmHg (P less than 0.05) but did not alter heart rate. ANG II ivt caused a dose-related drinking response, with a positive correlation between the amount of water drunk during ivt ANG II infusion and the increase in arterial pressure. Infusions of ANG II at 50 ng.kg-1.min-1 ivt were associated with decreased plasma osmolality and potassium concentration and increased plasma vasopressin concentration.
Measurements of blood flow to individual glomeruli in the ophidian kidney
Authors: Yokota S. D. , Dantzler W. H.
Published: December 2017

Continuous measurements of the instantaneous rate of blood flow to individual glomeruli in a normal vertebrate kidney were made in the garter snake Thamnophis sirtalis. Epifluorescence video microscopy was used to visualize and record blood flow in the afferent arterioles of superficial nephrons. The dual-slit method was used for the determination of red blood cell (RBC) velocity from the video replay. Simultaneous measurements of the vessel diameter allowed the continuous determination of the instantaneous rate of blood flow. A total of 100 glomeruli was surveyed in 12 animals. These glomeruli displayed both constant and highly variable rates of blood flow, with 21% of all nephrons displaying intermittent glomerular perfusion. The mean single-nephron blood flow rate (SNBFR) for all individuals was 23.9 +/- 10.3 (SD) nl/min (n = 12). The percentage of nephrons with intermittent flow for an individual animal increased significantly with increasing plasma osmolality. Intermittency was associated with low SNBFR values; SNBFR averaged 13.5 +/- 10.2 (SD) nl/min (n = 21) in intermittent nephrons and 29.2 +/- 19.0 (SD) nl/min (n = 79) in continuous flow nephrons, the difference being significant (P less than 0.001). Nephrons with continuous perfusion displayed a much greater range of SNBFR values than intermittent nephrons. This suggests that, although changes in whole kidney glomerular filtration rate (GFR) in reptiles need not involve glomerular intermittency, intermittency may lower GFR.
Atrial natriuretic peptide induces sustained natriuresis in conscious dogs
Authors: Mizelle H. L. , Hildebrandt D. A. , Gaillard C. A. , Brands M. W. , Montani J. P. , Smith M. J. , Hall J. E.
Published: December 2017

Although acute infusions of atrial natriuretic peptide (ANP) often cause natriuresis, these effects are not sustained, possibly because of reductions in arterial pressure or other compensatory adaptations. The aim of this study was to determine whether physiological increases in intrarenal ANP levels cause sustained natriuresis if changes in arterial pressure and other neurohumoral influences that might obscure the renal responses are controlled. Changes in renal function were quantitated during chronic unilateral renal arterial infusion of ANP at rates of 1, 2, and 4 ng.kg-1.min-1 in conscious dogs (n = 7) with the urinary bladder split to allow continuous measurement of renal excretion in the ANP-infused and contralateral, vehicle-infused kidneys. There was no change in mean arterial pressure at any infusion rate. During 1 ng.kg-1.min-1 infusion of ANP for 5 days, the renal excretory responses were small and variable. However, during 2 and 4 ng.kg-1.min-1 ANP infusion for 7 days, sodium excretion averaged 37.2 +/- 10.0 and 134.8 +/- 19.0% greater, respectively, in the ANP-infused kidneys compared with the vehicle-infused kidneys but there were no changes in glomerular filtration rate or effective renal plasma flow. These results demonstrate that when compensatory changes in arterial pressure and neurohumoral factors are controlled, ANP, at physiological concentrations, causes marked increases in renal excretion. This study supports the concept that ANP's effects to increase renal excretory capability could play a role in long-term control of arterial pressure and body fluid homeostasis.
An improved method for recording blood pressure in the tethered monkey
Authors: Talan M. I. , Engel B. T.
Published: December 2017

Existing tethering systems intended for continuous recording of blood pressure incur two major problems: 1) vertical movements of the animal in the cage produce a significant error in measured pressure introduced by the change in distance between the pressure transducer and the highest point of the infusion system and 2) the necessity for repeated zero adjustment of the pressure transducer requires sedation of the animal and disconnection of the catheter. Continuous infusion and a one-way valve in the infusion line in proximity to the pressure transducer will eliminate the error of measurement related to vertical movement of the animal. A remotely controlled, two-way solenoid valve can close the catheter line and open the pressure transducer to atmospheric pressure, thereby permitting repeated zero adjustment without sedation of the animal and disconnection of the catheter. Eliminating the need to disconnect the catheter will significantly reduce the risk of adventitious infection.
Role of aldosterone in angiotensin II-induced hypertension in rats
Authors: Kanagy N. L. , Pawloski C. M. , Fink G. D.
Published: December 2017

Initial experiments demonstrated that a 1-h infusion of 10 ng/min angiotensin II (ANG II) into rats causes an increase in plasma aldosterone concentration (PAC) and that chronic administration of aldosterone alone to rats on increased sodium intake causes hypertension. We therefore hypothesized that a portion of the hypertensive effect of chronic ANG II infusion is accompanied by and dependent on chronic release of aldosterone. To test this hypothesis, 10 ng/min ANG II or saline was infused into chronically instrumented rats housed in metabolism cages. Fifteen rats were maintained on a high sodium intake (6 meq/day); 10 received ANG II and 5 received saline. Ten other rats were maintained on a normal sodium intake (2 meq/day); five received ANG II and five received saline. PAC was measured using a commercial radio-immunoassay kit. Mean arterial pressure (MAP), heart rate, water intake, urine output, and urine electrolytes were measured daily during 3-day control, 16- or 28-day infusion, and 4-day recovery periods. Compared with saline-infused rats, ANG II-infused rats on high sodium intake had normal values for all variables except MAP, which was significantly elevated during ANG II infusion. In the normal sodium group, none of the variables were consistently different during ANG II infusion compared with control. These results suggest that ANG II-induced hypertension in the rat is sodium dependent, that plasma aldosterone does not play a major role in ANG II-induced hypertension in the rat, and that a small chronic increase in circulating ANG II does not necessarily lead to a detectable sustained increase in PAC.
Plasma profiles of IL-6 and TNF with fever-inducing doses of lipopolysaccharide in dogs
Authors: LeMay D. R. , LeMay L. G. , Kluger M. J. , D'Alecy L. G.
Published: December 2017

This study was designed to test the tumor necrosis factor (TNF) WEHI 164 clone 13 bioassay and the interleukin 6 (IL-6) B9 bioassay for sensitivity to endogenously produced dog TNF and IL-6 and then to use these assays to examine the associations between these cytokines and lipopolysaccharide (LPS)-induced fever. When dogs were injected with LPS (40, 10, 1, 0.1, and 0.01 microgram/kg), the resulting fever was dose dependent. A plot of plasma cytokine changes over time following LPS injections showed that the plasma TNF-like activity appeared to increase in an all-or-none dose response, whereas the increase in plasma IL-6-like activity appeared to be log dose dependent. Plasma TNF-like and IL-6-like activity were then separately plotted against temperature change (fever). Statistical analysis supported the interpretation that both TNF-like and IL-6-like activity were related to LPS-fever in an all-or-none manner, with IL-6 having a threshold region. We conclude that if these cytokines are circulating mediators of fever, they may induce fever in an all-or-none fashion.
Effect of intrarenal renin inhibition on renal hemodynamics and excretory function
Authors: Verburg K. M. , Kadam J. R. , Young G. A. , Rosenberg S. H. , Kleinert H. D.
Published: December 2017

This study was designed to investigate in sodium-depleted monkeys the renal hemodynamic and excretory effects resulting from blockade of the renin-angiotensin system induced by intrarenal infusion of the primate-selective renin inhibitor A-65317. Intrarenal infusion of A-65317 (n = 6) at a dose of 0.01 micrograms.kg-1.min-1 elicited an increase (P less than 0.05) in renal blood flow (RBF) from 43.5 +/- 2.7 to 49.4 +/- 4.4 ml/min and glomerular filtration rate (GFR) from 6.3 +/- 0.3 to 6.9 +/- 0.4 ml/min, with no significant changes in mean arterial pressure (MAP) or plasma renin activity (PRA). Increases (P less than 0.05) in the urine flow rate (0.18 +/- 0.04 to 0.28 +/- 0.04 ml/min) and the fractional excretion of sodium (0.18 +/- 0.06 to 0.35 +/- 0.13%) were also observed. After a recovery period, the intrarenal infusion dose of A-65317 was increased to 0.1 microgram.kg-1.min-1 and RBF increased (P less than 0.05) from 42.9 +/- 3.9 to 53.0 +/- 3.7 ml/min in conjunction with a significant 85 +/- 4% inhibition of PRA and a 14 +/- 4 mmHg reduction in MAP. GFR and electrolyte excretion remained at control levels. Intrarenal infusion of vehicle (n = 6) had no significant effect on any of the variables studied. In a separate group of monkeys, intravenous (iv) infusion of A-65317 at 0.01 microgram.kg-1.min-1 (n = 5) did not result in significant changes from control.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of converting-enzyme inhibition on renal response to ANF in rats with experimental heart failure
Authors: Abassi Z. , Haramati A. , Hoffman A. , Burnett J. C. , Winaver J.
Published: December 2017

Increased activity of the renin-angiotensin system is thought to play a major role in the pathogenesis of salt retention and edema formation in congestive heart failure. The present study evaluates the effects of chronic inhibition of angiotensin-converting enzyme on the response to infusion of exogenous atrial natriuretic factor (ANF) in salt-retaining rats with chronic arteriovenous (a-v) fistula, an experimental model of high-output congestive heart failure. Administration of ANF in incremental doses (5-50 micrograms.kg-1.h-1) to Inactin-anesthetized, sham-operated control rats resulted in dose-dependent increases in urine flow, sodium excretion, and glomerular filtration rate, and significant decreases in mean arterial blood pressure. These effects of atrial peptide were markedly attenuated in salt-retaining rats with a-v fistula. However, chronic oral treatment with the angiotensin-converting-enzyme inhibitor enalapril restored the natriuretic response of sodium-retaining rats with a-v fistula to high doses of ANF. At a dose of 50 micrograms.kg-1.h-1, fractional excretion of Na (FENa) in a-v fistula rats given enalapril was 4.0 +/- 0.5%, which was significantly greater than that in a-v fistula rats without enalapril (0.5 +/- 0.4%, P less than 0.05) and not different from the response in sham-control rats (4.9 +/- 0.7%). The improvement in the natriuretic response after enalapril was not associated with a significant increase in GFR and occurred despite a decrease in mean arterial pressure. Moreover, chronic enalapril treatment did not significantly alter the plasma levels of immunoreactive ANF in either the sham controls or in the rats with a-v fistula.(ABSTRACT TRUNCATED AT 250 WORDS)