bluuebunny/crossref_metadata_2025 huggingface dataset:
L-arginine analogues inhibit aldosterone secretion in rats
Authors: Simmons J. C. , Freeman R. H.
Published: December 2017

L-Arginine analogues, e.g., NG-nitro-L-arginine methyl ester (L-NAME), increase arterial pressure and suppress renin release in the rat. On the basis of these observations, it was hypothesized that L-arginine analogues also would attenuate aldosterone secretion. This hypothesis was tested in anesthetized rats treated with L-NAME or NG-nitro-L-arginine (L-NNA, 185 mumol/kg ip). The aldosterone secretion rate, plasma renin activity, and adrenal blood flow were attenuated in rats treated with L-NAME and L-NNA compared with control animals. Similar experiments were performed in anephric rats to examine the effects of L-NAME on aldosterone secretion independent of the circulating reninangiotensin system. The administration of L-NAME reduced adrenal blood flow but failed to reduce aldosterone secretion in these anephric rats. Bilateral nephrectomy reduced plasma renin activity essentially to undetectable levels in these animals. In a third series of experiments, two groups of anephric rats were infused with angiotensin II (3 micrograms/kg body wt iv) to provide a stimulus for aldosterone secretion. Aldosterone secretion and adrenal blood flow were markedly reduced in angiotensin II-infused rats pretreated with L-NAME compared with the control anephric animals infused with angiotensin II. Overall these results suggest that L-arginine analogues attenuate aldosterone secretion by inhibiting the adrenal steroidogenic effects of endogenous or exogenous angiotensin II and/or by reducing plasma levels of renin/angiotensin.
Age, gender, and vasopressin affect survival and brain adaptation in rats with metabolic encephalopathy
Authors: Arieff A. I. , Kozniewska E. , Roberts T. P. , Vexler Z. S. , Ayus J. C. , Kucharczyk J.
Published: December 2017

Children and menstruant women are far more likely than men to develop metabolic brain damage from hyponatremia. We evaluated brain adaptation and mortality from hyponatremia in male and female rats of three different age groups. With acute hyponatremia, the mortality was 84% in prepubertal rats vs. 15% in adults and 0% in elderly rats. With chronic hyponatremia, mortality was 13% in adult males vs. 62% in females. Testosterone pretreatment significantly decreased mortality (from 62 to 9% in adult females, and from 100% to zero in prepubertal rats), but estrogen significantly increased mortality (from 13 to 44% in adult males). With acute hyponatremia in adult rats, brain sodium was significantly decreased (-17%), but in prepubertal rats it was actually increased (+ 37%). Cerebral perfusion during chronic hyponatremia was significantly impaired in adult females vs. males or controls (P < 0.01). Neither vasopressin administration nor chronic hyponatremia induced with desmopressin resulted in any mortality or decrement of cerebral perfusion. Thus age, gender, and the cerebral effects of vasopressin are major determinants of mortality in experimental metabolic encephalopathy.
Physiological correlates of vagal nerve innervation in lower vertebrates
Authors: Preston E. , Courtice G. P.
Published: December 2017

In lower vertebrates, cardiac vagal innervation shows less anatomic complexity and specialization than in mammals. To assess the physiological development of vagal specialization in the vertebrates, we investigated cardiac chronotropic effects of electrical stimulation of left and right vagus nerves separately and the interactions between both nerves in anesthetized animals from three vertebrate groups, toad (Bufo marinus), shark (Heterodontus portusjacksoni), and lizard (Physignathus lesueurii). Atropine-sensitive slowing was effected equally by left or right vagi in all species, and chronotropic effects of simultaneous stimulation were the same as the sum of left and right responses. In sharks and lizards, no slowing after atropine was detected (10 Hz stimulation). In toads, after atropine, cardiac slowing was elicited equally by left or right vagal stimulation > 2 Hz. Simultaneous stimulation of both vagi after atropine caused significantly greater slowing than the sum of left and right responses. The results suggest even distribution of left and right vagal nerve endings to pacemaker cells, and limited competition for cardiac receptor sites in lower vertebrates.
Subdiaphragmatic vagotomy blocks induction of IL-1 beta mRNA in mice brain in response to peripheral LPS
Authors: Laye S. , Bluthe R. M. , Kent S. , Combe C. , Medina C. , Parnet P. , Kelley K. , Dantzer R.
Published: December 2017

To test the possibility that the vagus nerve is involved in the communication between the immune system and the brain, we injected sham-operated and vagotomized mice with physiological saline or lipopolysaccharide (LPS; 400 micrograms/kg ip). Vagotomy attenuated LPS-induced depression of general activity measured 2 h after treatment but did not alter the increase in plasma levels of IL-1 beta in response to LPS. In addition, vagotomy abrogated the LPS-induced increase in the levels of transcripts for IL-1 beta, as determined by semiquantitative polymerase chain reaction after reverse transcription, in the hypothalamus and hippocampus, but not in the pituitary of vagotomized mice. This relationship between the effects of vagotomy on the behavioral effects of LPS and the LPS-induced brain expression of IL-1 beta mRNA indicates that vagal afferent fibers play a prominent role in the pathways of communication between the immune system and the brain.
Hormonal-sympathetic interactions in long-term regulation of arterial pressure: an hypothesis
Authors: Brooks V. L. , Osborn J. W.
Published: December 2017

The importance of the sympathetic nervous system in short-term regulation of arterial pressure is well accepted. However, the question of whether neural systems participate in long-term control of pressure has been debated for decades and remains unresolved. The principal argument against such a control system is that arterial baroreceptors adapt to sustained changes in arterial pressure. In addition, denervation of baroreceptors has minimal to no effect on basal levels of arterial pressure chronically. This argument assumes, however, that baroreceptors provide the primary chronic feedback signal to the central nervous system. An alternate model is proposed in which circulating hormones, primarily arginine vasopressin and angiotensin II, provide a long-term afferent signal to the central nervous system via binding to specific receptors in central sites lacking a blood-brain barrier (circumventricular organs). Studies suggest that the release of the hormones and the sympathetic response to alterations in their plasma concentrations are nonadaptive but may be gated by baroreceptor input. Evidence that this "hormonal-sympathetic reflex" model may explain the long-term alterations in sympathetic activity in response to chronic salt depletion and salt loading as well as congestive heart failure is presented. Finally, the role of an impaired hormonal sympathetic reflex in hypertension, specifically salt-dependent hypertension, is discussed.
Role of prostaglandins and nitric oxide in mediating renal response to volume expansion
Authors: Salazar F. J. , Llinas M. T. , Gonzalez J. D. , Quesada T. , Pinilla J. M.
Published: December 2017

The objective of the present study was to examine, in anesthetized dogs, the possible interaction between prostaglandins (PG) and nitric oxide (NO) in mediating the renal response to an extracellular volume expansion (ECVE). The renal response to ECVE was examined during 1) intrarenal infusion of a PG synthesis inhibitor, 2) intrarenal administration of a NO synthesis inhibitor, and 3) simultaneous inhibition of PG and NO synthesis in the right kidney. Compared with the control group, the ECVE-induced increments in sodium excretion and fractional excretion of lithium were not affected by the PG synthesis inhibition. The NO synthesis inhibition did not induce changes in renal hemodynamics but reduced (P < 0.05) the ECVE-induced increments in sodium excretion and fractional excretion of lithium. When PG and NO synthesis were simultaneously inhibited in the right kidney during ECVE, there were no significant differences between the renal hemodynamics of both kidneys. However, compared with the left kidney, the ECVE-induced changes in sodium excretion and fractional excretion of lithium were reduced in the right kidney. The reduction of the natriuretic response to ECVE was greater (P < 0.05) than in the dogs where only NO synthesis was inhibited. Our results suggest a major interaction between NO and PG in mediating the renal hemodynamic and excretory responses to an increase in extracellular volume.
Kinetic analysis of muscarinic receptors in human brain and salivary gland in vivo
Authors: Hiramatsu Y. , Eckelman W. C. , Carrasquillo J. A. , Miletich R. S. , Valdez I. H. , Kurrasch R. H. , Macynski A. A. , Paik C. H. , Neumann R. D. , Baum B. J.
Published: December 2017

Previous studies in rats have suggested that the muscarinic acetylcholine receptor (mAChR) antagonist (S)-3-quinuclidinyl-(S)-4-[123I]iodobenzilate [(SS)-IQNB] may be useful for the in vivo evaluation of mAChRs in humans as a control for the higher-affinity compound (RR)-IQNB. We have directly tested this hypothesis and examined the distribution of mAChRs in brain regions and parotid glands of healthy human volunteers in vivo using (RR)- and (SS)-IQNB (relatively high- and low-affinity antagonists, respectively), planar imaging, and pharmacokinetic analysis. This is the first in vivo study of mAChRs in humans that has employed stereoisomeric ligands and metabolic analysis to determine specific receptor binding. We observed that (SS)-IQNB showed much faster clearance from blood than (RR)-IQNB and different metabolite profiles. Also, the transport kinetics of the enantiomers were different. The estimated binding potential (approximately Bmax/Kd) of (RR)-IQNB was highest in two cortical regions, intermediate in parotid gland, and lowest in cerebellum. The aggregate results show that in humans (SS)-IQNB does not act as an ideal general probe to measure the nonspecific IQNB distribution. However, (RR)-IQNB does appear to have value when used for studies of human brain mAChRs.
Swim training alters sympathoadrenal and endocrine responses to hemorrhage in borderline hypertensive rats
Authors: McCoy D. E. , Steele J. E. , Cox R. H. , Wiley R. L.
Published: December 2017

Swim training alters cardiovascular, sympathoadrenal, and endocrine responses to hemorrhage in borderline hypertensive rats (BHR). The effects of 10, 20, and 30% blood volume hemorrhages on cardiovascular, sympathoadrenal, and endocrine function in swim-trained (T; 2 h/day, 5 day/wk for 10-12 wk) and age-matched, untrained, sedentary, control (UT) borderline hypertensive rats (BHR) were assessed. Heart rate (HR) in UT BHR was significantly greater during the baseline (rest) period than T BHR. HR increased slightly from baseline in both groups after 10% hemorrhage but was significantly decreased in both groups after 20 and 30% hemorrhages. The decrease was eliminated by atropine (1 mg/kg iv). Systolic (SBP) and diastolic (DBP) blood pressures decreased significantly after 20 and 30% hemorrhages in both T and UT BHR but were not different between the groups at these times. Plasma norepinephrine levels were significantly increased above baseline after 20 and 30% hemorrhages in UT BHR and were significantly greater in UT BHR than T BHR after 30% hemorrhage. Plasma glucose levels increased significantly after 30% hemorrhage in both groups but were significantly greater in UT BHR than T BHR. Both plasma norepinephrine and plasma epinephrine levels showed strong positive correlations with plasma glucose. After 20 and 30% hemorrhages, plasma insulin levels were unchanged in T BHR but were significantly decreased in UT BHR. Plasma insulin levels were significantly less in UT than T BHR after 30% hemorrhage. These results suggest that swim training alters the effect that hemorrhage exerts on endocrine and sympathoadrenal function in BHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypothalamic sites mediating cardiovascular effects of microinjected bicuculline and EAAs in rats
Authors: De Novellis V. , Stotz-Potter E. H. , Morin S. M. , Rossi F. , DiMicco J. A.
Published: December 2017

Microinjection of gamma-aminobutyric acidA receptor antagonist bicuculline methiodide (BMI) into either the dorsomedial hypothalamic nucleus (DMH) or the nearby paraventricular hypothalamic nucleus (PVN) has been reported to evoke marked tachycardia and modest pressor effects. We compared the effects of microinjecting BMI and excitatory amino acids (EAAs) into 1) the DMH, 2) the PVN, and 3) an intermediate area between the two nuclei. In conscious rats, microinjection of (in pmol) 10 BMI, 0.5 kainic acid, or 5 N-methyl-D-aspartate into the DMH markedly increased heart rate and slightly elevated arterial pressure, whereas injections into other regions provoked changes that progressively declined in magnitude with increasing distance from the nucleus. A similar pattern was evident in urethan-anesthetized rats, where the shortest latency to onset of BMI-induced increases in heart rate was seen after injection into the DMH. These findings demonstrate that the cardiovascular changes seen after microinjection of BMI or EAAs into the medial hypothalamus result from an action in the DMH and not from spread to the PVN.
Changes in circadian rhythms of body temperature and sleep in old rats
Authors: Li H. , Satinoff E.
Published: December 2017

We examined the relationship between circadian rhythms of body temperature (CTR) and sleep in adult and old female rats. Body temperature was recorded telemetrically for months and sleep for 24 h in a 12:12-h light-dark cycle at 23 degrees C. Some old rats had robust CTRs (old good), and some had unstable or absent CTRs (old unstable). Old unstable rats had lower daily mean body temperatures, smaller daily amplitudes, and a more advanced CTR phase than adult rats and old good rats. Old good rats matched adult rats in all measures. In old good rats, circadian parameters of sleep were normal, whereas in old unstable rats the amplitudes of slow-wave and rapid eye movement sleep were decreased, although the amounts were equivalent. Rhythmic parameters of sleep correlate well with the stability or instability of the CTR, whereas homeostatic regulation of rapid eye movement and slow-wave sleep do not seem to be impaired during aging and are independent of the stability of the CTR.
Cellular oxygen consumption depends on body mass
Authors: Porter R. K. , Brand M. D.
Published: December 2017

Hepatocytes were isolated from nine species of mammal of different body mass (and standard metabolic rate). The cells were incubated under identical conditions and oxygen consumption measured. The rate of oxygen consumption (per unit mass of cells) scaled with body mass with exponent -0.18. In general, there was a 5.5-fold decrease in oxygen consumption rate with a 12,500-fold increase in body mass. The decrease in oxygen consumption rate was not due to an increase in cell volume with increasing body mass but to a decrease in intrinsic metabolic activity of the cells. This novel finding confirms and explains the decrease in oxygen consumption rate measured in tissue slices from larger mammals by H. A. Krebs (Biochim. Biophys. Acta 4: 249-269, 1950) and recently by P. Couture and A. J. Hulbert [Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R641-R650, 1995].
Natriuretic peptide receptors are expressed during cerebral growth in the fetal rat
Authors: Brown J. , Zuo Z.
Published: December 2017

Autoradiography of frozen sections of fetal rat brain shows that receptor-like binding sites for atrial and C-type natriuretic peptides (ANP and CNP) occur in the generative juxtaventricular zone of the telencephalon after the 12th embryonic day (E12). These sites avidly bind both ANP and CNP. They thus resemble the cloned NPR-C type of natriuretic peptide receptor. Covalent cross-linking of 3-[125I]iodo-O-tyrosyl CNP-(1-22) and 3-[125I]iodo-28-tyrosyl rat ANP-(1-28) to membrane proteins from E16 telencephala labels a single protein band on reducing sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The protein has high affinities for ANP and CNP and a molecular mass of 60-70 kDa under reducing conditions, consistent with reduced NPR-C. However, because the telencephalic protein has unusual physicochemical properties in SDS under nonreducing conditions it was not possible to assess whether this protein can form disulfide-bridged dimers like NPR-C. CNP-(1-22) was a full agonist and ANP-(1-28) was a partial agonist of guanosine 3',5'-cyclic monophosphate (cGMP) production by E16 telencephalon. C-ANP, a synthetic ligand of NPR-C, antagonized CNP-(1-22)-mediated cGMP production. The results imply that either the NPR-C-like telencephalic receptor modulates the level of cGMP or a guanylate cyclase-coupled receptor, such as the 120-kDa B-type NPR, for which CNP-(1-22) is a full agonist, is present at levels insufficient to be detected by autoradiography or protein labeling.(ABSTRACT TRUNCATED AT 250 WORDS)
Sodium specificity of salt appetite in Fischer-344 and Wistar rats is impaired by chorda tympani nerve transection
Authors: Breslin P. A. , Spector A. C. , Grill H. J.
Published: December 2017

Unlike other rat strains, the sodium-replete Fischer-344 (F344) strain shows no innate preference for NaCl and displays more aversive and fewer ingestive oral motor responses to orally infused NaCl when tested in sodium balance. Despite these differences, F344 rats show an increase in preference for NaCl in response to sodium depletion. The present study was designed to determine whether the salt appetite of sodium-depleted F344 rats is cation specific and whether such selectivity is mediated in part by an intact chorda tympani nerve. Sodium-depleted (10 mg furosemide) F344 (n = 13) and Wistar (n = 16) rats were permitted repeated access to nine stimuli (water, and 0.05 and 0.3 M NaCl, KCl, NH4Cl, and CaCl2), presented randomly in 10-s trials. One-half of the rats had their chorda tympani nerve sectioned (CTX). Under conditions of sodium depletion, both strains discriminated NaCl from other chloride salts. CTX significantly impaired the selectivity of the licking behavior in both strains, suggesting that sodium-specific licking is partially mediated by anterior tongue taste receptors. These findings suggest that both sodium-depleted F344 and Wistar rats are comparable in their abilities to recognize NaCl, to distinguish it from other salts, and to respond selectively to it, despite the fact that sodium-replete F344 and Wistar rats differ greatly in their NaCl preference.
Galanin and the galanin antagonist M40 do not change fat intake in a fat-chow choice paradigm in rats
Authors: Corwin R. L. , Rowe P. M. , Crawley J. N.
Published: December 2017

The neuropeptide galanin has been proposed to play a role in the regulation of fat intake. The purpose of the present investigation was to determine if galanin and the galanin receptor antagonist M40 would have selective effects on fat intake in a fat-chow choice paradigm in rats. Rats were adapted to 22-h access to chow alone and 2-h daily access to separate sources of fat and chow in the early dark cycle. Galanin (300 pmol, 1 nmol) or M40 (2-500 pmol) was microinjected bilaterally into the paraventricular nucleus of the hypothalamus (PVN) before the 2-h choice period, and chow and fat intake were measured. M40 had no effect on chow or fat intake. Galanin stimulated chow intake and increased the ratio of chow to fat consumed but had no significant effect on fat intake alone. These results suggest that endogenous galanin in the PVN may not play a primary role in the regulation of fat intake when fat is available in addition to a nutritionally balanced diet.
Endocrine consequences of prenatal sodium depletion prepare rats for high need-free NaCl intake in adulthood
Authors: Galaverna O. , Nicolaidis S. , Yao S. Z. , Sakai R. R. , Epstein A. N.
Published: December 2017

Offspring of dams that were repeatedly sodium depleted during late pregnancy (at days E14, E17, and E20) expressed high need-free 3% NaCl intake in adulthood. Need-free 3% NaCl intake was greater in females, thereby respecting the sexual dimorphism of this behavior, and was increased further by successive sodium depletion in adulthood. Offspring from dams that had been sodium depleted while receiving the angiotensin-converting enzyme inhibitor, captopril, showed a need-free NaCl intake similar to that of control rats nonneonatally sodium depleted. Trunk blood taken from dams at day E18, i.e., 24 h after the second treatment, revealed that sodium depletion produced marked increases in the dam's plasma angiotensin (ANG) II and aldosterone that were not present when dams were treated with captopril during sodium depletion, even though both groups displayed a similar hyponatremia. We therefore propose that, during prenatal sodium depletion, the activation of the angiotensin-aldosterone system rather than the loss of sodium itself is responsible for the modification in need-free NaCl intake behavior. Finally, we suggest that, during pregnancy, ANG II may have an organizational effect on the neural substrate in the fetal brain that subserves subsequent NaCl intake behavior.
Cross fostering between normal and sodium-restricted rats: effects on peripheral gustatory function
Authors: Phillips L. M. , Stewart R. E. , Hill D. L.
Published: December 2017

Rats restricted of dietary NaCl prenatally and thereafter exhibit abnormally low electrophysiological chorda tympani taste responses to sodium stimuli as adults. Recovery of responses can be induced by ingestion of NaCl, even at adulthood. To examine whether milk from sodium-replete mothers enables functional recovery in sodium-restricted rats, we recorded multifiber chorda tympani responses in adult animals that had been cross fostered during the suckling period. Sodium-restricted animals cross fostered to control dams for postnatal weeks 1 and 2 did not recover normal sodium sensitivity. Surprisingly, control pups crossed to sodium-restricted mothers from postnatal days 1 to 14 showed an exaggerated response to NaCl as adults. These results indicate that milk from normal mothers ingested during postnatal weeks 1 and 2 is not sufficient to restore gustatory function in sodium-restricted rats. Importantly, it also appears that events occurring during the early suckling period of control rats determine long-term taste sensitivities to sodium.
Multihormonal regulation of nephron epithelia: achieved through combinational mode?
Authors: De Rouffignac C.
Published: December 2017

The kidney is the main organ regulating composition of body fluids. A considerable number of hormones control the activity of renal cells to maintain hydromineral equilibrium. It becomes more and more difficult to interpret this multihormonal control in terms of regulatory processes. To illustrate this complexity, the hormonal regulation of electrolyte transport in the nephron thick ascending limb is taken as an example. This nephron segment is largely responsible for two kidney functions: the urinary-concentrating ability (by its capacity to deliver hypertonic sodium chloride into the medullary interstitium) and regulation of magnesium excretion into final urine. Six hormones are presently identified as acting on the transport of both sodium chloride and magnesium ions in this nephron segment. Therefore, the pertinent question is how the thick ascending limb and, hence, the kidney, is capable of regulating water balance independently from magnesium balance. It is proposed that the hormones act in combination: circulating levels of the individual hormones acting on these cells may determine the configuration of the paracellular and transcellular transport pathways of the epithelium either in the “sodium” or “magnesium” mode. The configuration would depend on the distribution and activity of the receptor at the surface of the basolateral membrane in contact with the circulating hormones. This distribution along with stimulation of respective signal transduction pathways would lead to the final biological effects. It is already known that the distribution of cell receptors may vary according to factors such as age, nutritional variability, hormonal status, degree of desensitization of the receptors, etc. The modulation of hormonal responses would depend therefore on the degree of coupling of hormone-receptor complexes to different intracellular transduction pathways and on the resulting negative and/or positive interactions between these pathways.
Glomerular actions of arginine vasotocin in the in situ perfused trout kidney
Authors: Amer S. , Brown J. A.
Published: December 2017

Recent measurements of plasma arginine vasotocin (AVT) in teleost fish suggest circulating concentrations of 10(-10)-10(-12)M. Previous studies of the renal actions of AVT in vivo suggest both diuretic and antidiuretic effects, but at unknown circulating concentrations. We have investigated the renal actions of 10(-9) and 10(-11) M AVT in vitro using an in situ perfused kidney preparation of rainbow trout (oncorhynchus mykiss). AVT increased vascular resistance (56%), reduced perfusate flow (P < 0.001), and increased interrenal aortic pressure (P < 0.001). AVT resulted in dose-dependent decreases in urine flow rates, glomerular filtration rates, and tubular transport maxima for glucose. AVT at 10(-11) M reduced relative free water clearances (P < 0.01), but urine/plasma inulin ratios were unchanged, whereas 10(-9)M AVT reduced urine/plasma inulin ratios (P < 0.01) and increased relative free water clearances (P < 0.05). The filtering population of glomeruli was reduced by both 10(-11) and 10(-9)M AVT to approximately one-third of the glomeruli, and a similar population of arterially perfused but nonfiltering glomeruli emerged. These results demonstrate that physiological concentrations of AVT have potent glomerular antidiuretic action in the trout, reducing the number of functional glomeruli, and imply reduced individual nephron filtration rates.
Intracellular pH in snake renal proximal tubules
Authors: Kim Y. K. , Dantzler W. H.
Published: December 2017

Intracellular pH (pHi) was studied in isolated proximal renal tubules of garter snakes (Thamnophis spp.) with oil-filled lumens under control conditions [N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered medium with pH 7.4 at 25 degrees C] and in response to NH4Cl pulse. pHi was measured with the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF). Control resting pHi (7.1) and acidification in response to NH4Cl pulse (minimum pHi, 6.6) were essentially the same in snake tubules with oil-filled lumens or perfused lumens and in rabbit S2 proximal tubules with oil-filled lumens. Rate of recovery of pHi (dpHi/dt) from acid to resting level in snake tubules (2.5 x 10(-3) pH U/s was about one-third of that in rabbit tubules. Resting pHi and dpHi/dt from acid to resting level were Na+ dependent in the distal portion but not the proximal portion of snake proximal tubules. However, dpHi/dt was not influenced by amiloride or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid in snake proximal tubules, suggesting that the effect of Na+ on dpHi/dt and resting pHi may involve membrane potential. This study also indicates that oil-filled lumens do not interfere with measurements of resting pHi and do permit evaluation of pHi regulation at the basolateral membrane without complications from transport at the luminal membrane.
Cerebral lactate metabolism in near-term fetal sheep
Authors: Turbow R. M. , Curran-Everett D. , Hay W. W. , Jones M. D.
Published: December 2017

The present study was designed to see if lactate can cross the blood-brain barrier of the near-term fetal sheep and replace glucose as an oxidative substrate during normoglycemia and acute insulin-induced hypoglycemia. Cerebral uptake of glucose, oxygen, lactate, and [14C]lactate as well as cerebral production of 14CO2 were measured under three conditions: 1) normoglycemia-normolactemia, 2) acute hypoglycemia-normolactemia, and 3) hypoglycemia-steady-state hyperlactemia. Although uptake of tracer [14C]lactate was consistent, there was no net uptake of unlabeled lactate during either normoglycemia or hypoglycemia. When arterial lactate concentration was raised from 2.2 +/- 0.5 to 3.3 +/- 0.4 (SE) mM by sodium lactate infusion, however, lactate was taken up. Comparison of cerebral [14C]lactate uptake with 14CO2 production indicated that the principal metabolic fate of lactate is oxidation. At increased concentrations, exogenous lactate accounted for approximately 7% of cerebral oxygen consumption. This study demonstrates that lactate crosses the blood-brain barrier of the near-term fetal sheep, is oxidized, and at elevated concentrations can partially replace glucose as an oxidative substrate during acute hypoglycemia.
Pancreatic somatostatin-14 and somatostatin-25 release in rainbow trout is stimulated by glucose and arginine
Authors: Eilertson C. D. , Sheridan M. A.
Published: December 2017

Previous work suggested that teleost fish possess two somatostatin (SS) genes. Regulation of differential secretion of SS gene I (SS-25) and SS gene II products (SS-14) by nutrients was studied using rainbow trout. Hemi-islets were cultured in medium containing different concentrations of glucose and arginine. SS-14 and insulin were determined by radioimmunoassay; SS-25 was determined by a novel enzyme-linked immunosorbent assay. Glucose stimulated SS-25 release in a concentration-related manner, with 10 mM being the most effective concentration; at higher (25 mM) glucose, release decreased. Insulin levels in the medium also were found to be more elevated from islets incubated in 10 mM glucose than those incubated in 25 mM glucose. Maximum SS-14 release was observed at lower (1-5 mM) glucose concentrations. Arginine stimulated SS release so that maximum release of both SS forms occurred at the lowest glucose concentrations (1 mM). A concentration-related effect of arginine was observed on SS-25 release. The results of this study indicate that glucose and arginine regulate secretion of both pancreatic SS gene I and gene II products from rainbow trout islets, suggesting that two different pancreatic SS interact in nutrient homeostasis in this species.
Body energy status and the metabolic response to acute inflammation
Authors: Lennie T. A. , McCarthy D. O. , Keesey R. E.
Published: December 2017

An animal model of acute inflammation was used to examine how body energy status influences the syndrome of anorexia, negative nitrogen balance, and body weight loss typically seen in response to injury. Specifically, the metabolic response to acute inflammation was studied in rats of normal, elevated, or reduced body weights. Rats induced to overeat and gain weight prior to inflammation displayed protracted anorexia, greater subsequent weight loss, higher metabolic rates, and greater negative energy balance than rats of normal weight. Conversely, rats with reduced body weights displayed elevated food intakes, body weight gain, attenuated nitrogen loss, and normal rates of energy expenditure. Prior weight reduction did not affect postinflammation fever or levels of fibrinogen, iron, and interleukin-6-like activity, suggesting that the ability to mount an acute phase response was not impaired in weight-reduced rats. These results suggest that the usual postinflammation adjustments in body energy flux and body nitrogen are regulated components of a metabolic response to acute inflammation which renders normally protected sources of endogenous energy and substrate available for repair and recovery.
Interleukin-1 beta enhances spinal cord blood flow after intrathecal administration in the normal rat
Authors: Plata-Salaman C. R. , Kelly G. , Agresta C. , Taylor K. , Salzman S. K.
Published: December 2017

The effects of acute intrathecal recombinant human interleukin-1 beta (rhIL-1 beta) administration on spinal cord blood flow (SCBF), volume, and velocity were determined by laser-Doppler flowmetry in normal anesthetized rats with the use of a randomized and blinded protocol. The intrathecal administration of rhIL-1 beta (0.16-16 ng) produced a dose-dependent increase in SCBF that was not related to changes in blood pressure; arterial pH, PO2, PCO2; or spinal cord temperature. The IL-1 beta-induced enhancement of SCBF was directly proportional to the resultant elevation of spinal cord rhIL-1 beta content and was significantly correlated with an elevated blood velocity. The IL-1 receptor antagonist (IL-1ra) in concentrations 50- and 200-fold higher than IL-1 beta completely blocked the IL-1 beta-induced increase in SCBF when both compounds were administered concomitantly, but when administered alone, IL-1ra did not affect SCBF or other parameters. This suggests that IL-1 beta action was mediated by a specific interaction with an IL-1 membrane receptor site. The results suggest a role of IL-1 beta in the regulation of spinal cord hemodynamics. A potential pharmacological approach using IL-1 agonists for the treatment of the delayed appearance of posttraumatic spinal ischemia is proposed.
Lateral parabrachial serotonergic mechanisms: angiotensin-induced pressor and drinking responses
Authors: Menani J. V. , Johnson A. K.
Published: December 2017

This study investigated the effects of bilateral injections of serotonergic receptor ligands into the lateral parabrachial nucleus (LPBN) on the pressor and dipsogenic responses induced by intracerebroventricular (i.c.v.) injection of angiotensin II (ANG II). Rats with stainless steel cannulas implanted bilaterally into the LPBN and into the left lateral ventricle were used to study i.c.v. ANG II-induced water intake and pressor responses. Pretreatment with the serotonergic 5-HT1/5-HT2 receptor antagonist methysergide (1-8 micrograms/200 nl) bilaterally injected into the LPBN increased the water intake induced by i.c.v. ANG II (50 ng/microliters) administered via the lateral ventricle, but pretreatment with methysergide (4 micrograms/200 nl) did not change the pressor response produced by i.c.v. ANG II. After bilateral injection of either serotonin (5-HT, 5 micrograms/200 nl) or the serotonergic 5-HT2a/5-HT2c receptor agonist (+/-)-2,5-dimetoxy-4-iodoamphetamine hydrochloride (DOI; 0.5-10 micrograms/200 nl) into the LPBN, the water intake induced by ANG II was significantly reduced. These results are consistent with Other observations indicating that the LPBN is associated with inhibitory mechanisms controlling water intake induced by ANG II treatment and suggest that serotonergic pathways may be involved in this effect.
Characterization of organic cation transport by avian renal brush-border membrane vesicles
Authors: Villalobos A. R. , Braun E. J.
Published: December 2017

Organic cations are actively secreted by the renal proximal tubule. Studies on perfused tubules and isolated membranes from mammals and reptiles have demonstrated that organic cations (OC) are transported across the luminal (brush-border) membrane by OC/H+ exchange. Our objective was to determine whether a similar mechanism was present in the avian kidney. Uptake of [14C]tetraethylammonium (TEA) was assayed under various ionic conditions by rapid filtration in brush-border membrane vesicles (BBMV) isolated from chicken kidney (Gallus domesticus). An outwardly directed proton gradient (pHin = 6.0: pHout = 7.5) stimulated concentrative TEA uptake. TEA/H+ exchange was saturable, having a maximal rate of uptake of approximately 25 nmol.mg protein-1.min-1 and a Michaelis constant for TEA of approximately 500 microM. TEA transport could be indirectly coupled to sodium transport. Unlabeled TEA, N'-methylnicotinamide (NMN), choline, cimetidine, mepiperphenidol, quinidine, quinine, and ranitidine markedly cis-inhibited uptake of [14C]TEA. However, the organic anions probenecid and p-aminohippurate poorly inhibited uptake. Unlabeled TEA and NMN also trans-stimulated [14C]TEA uptake. Thus, in avian renal BBMV, organic cations are transported by an OC/H+ exchange mechanism qualitatively similar to that present in mammals.
Cardiac output and peripheral resistance during larval development in the anuran amphibian Xenopus laevis
Authors: Hou P. C. , Burggren W. W.
Published: December 2017

Stroke volume (SV) and cardiac output (CO) were measured in anesthetized larvae of Xenopus laevis from hatching (3 mg) to the end of metamorphosis (approximately 1 g). CO and SV were calculated from videotaped images of the intact beating heart. SV increased from 2.4 x 10(-3) microliters at 3 mg body mass to 7.6 microliters at 1 g. CO increased from 0.25 microliter/min at 3 mg to 623 microliters/min at 1 g. With use of CO, along with arterial pressures from another study [P.-C. L. Hou and W. W. Burggren. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R1120-R1125, 1995], peripheral resistance and cardiac work were also calculated. Resistance decreased rapidly from 701 peripheral resistance units (PRU, mmHg.s.mm-3) at 3 mg body mass to 79 PRU at 20 mg and gradually declined toward 0.9 PRU at 1 g. Cardiac work increased from 0.06 dyn.mm at 3 mg body mass to 1.27 dyn.mm at 20 mg and then climbed sharply to 717 dyn.mm at 1 g. The general pattern of change in hemodynamic variables (except heart rate) during larval development is similar in Xenopus laevis and chick embryos, suggesting a common pattern for hemodynamic development in vertebrate embryos/larvae.
Regulation of muscle glucose transport and GLUT-4 by nerve-derived factors and activity-related processes
Authors: Megeney L. A. , Michel R. N. , Boudreau C. S. , Fernando P. K. , Prasad M. , Tan M. H. , Bonen A.
Published: December 2017

Glucose transport and GLUT-4 were examined in muscles in which activity and nerve-derived factors were eliminated (denervation) and in muscles in which only muscle activity was eliminated but in which nerve-derived factors were maintained [tetrodotoxin (TTX) treatment]. After 3 days of denervation, insulin-stimulated 3-O-methylglucose transport was markedly lowered in perfused rat hindlimb muscles (soleus, plantaris, and red and white gastrocnemius; < or = 35%). GLUT-4 was also decreased by 11-65% in denervated muscles. Blocking muscle activity with TTX superfusion of the sciatic nerve for 3 days reduced the insulin-stimulated glucose transport to the same extent as in the denervated muscles (P > 0.05). However, in soleus, plantaris, and red gastrocnemius muscles, GLUT-4 expression was reduced much less by TTX treatment than by denervation (P < 0.05). GLUT-4 mRNA abundance was decreased in denervated muscles but not in TTX-treated muscles. These results suggest that muscle activity largely regulates the insulin-signaling mechanisms of glucose transport and that nerve-derived trophic factors affect pretranslational events to regulate GLUT-4 expression.
Causes of differences in respiration rate of hepatocytes from mammals of different body mass
Authors: Porter R. K. , Brand M. D.
Published: December 2017

Resting O2 consumption of hepatocytes isolated from mammals ranging in mass from 20-g mice to 200-kg horses decreases with increasing body mass. The substrate oxidation system increases in activity with increasing body mass and mitochondrial proton leak and phosphorylation system decrease in activity, resulting in a higher mitochondrial membrane potential in hepatocytes from larger mammals. The absolute rates of O2 consumption due to nonmitochondrial processes, substrate oxidation, mitochondrial proton leak, and the phosphorylation system decrease with increasing body mass. These decreases are due partly to a decrease in mitochondrial number per cell and partly to decrease in mitochondrial inner membrane proton leakiness and in ATP turnover by cells from larger mammals. Quantitatively, the proportion of total cell O2 consumption by nonmitochondrial processes (13%) and oxidation of substrates (87%) and the proportions used to drive mitochondrial proton leak (19%) and the phosphorylation system (68%) are the same for hepatocytes from all mammals investigated. The effect of matched decreases in the rates of proton leak and of ATP turnover is to keep the effective amount of ATP synthesized per unit of O2 consumed relatively constant with body mass, suggesting that the observed value is optimal.
Hypothalamic response to starvation: implications for the study of wasting disorders
Authors: Schwartz M. W. , Dallman M. F. , Woods S. C.
Published: December 2017

Weight loss is a potent stimulus to food intake in normal individuals. The persistence of anorexia in wasting disorders, therefore, implies a failure of this adaptive feeding response. We describe a model for the normal hypothalamic response to starvation composed of the stimulation of neuronal pathways that promote energy intake and storage coupled with the inhibition of pathways that exert opposing effects. This model provides a framework for investigating disturbances of the normal hypothalamic response to weight loss and suggests a specific mechanism by which cytokines contribute to wasting in acquired immune deficiency syndrome and other cachexic disorders.
Endothelium-dependent relaxation is depressed at the macro- and microcirculatory levels during sepsis
Authors: Wang P. , Ba Z. F. , Chaudry I. H.
Published: December 2017

The objective of this study was to determine whether endothelium-derived nitric oxide (NO) production is reduced at the macrocirculatory and microcirculatory levels during sepsis. To examine this, rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 h after CLP (i.e., midpoint of hyperdynamic sepsis) or sham operation, the aorta and superior mesenteric artery were isolated. Responses to an endothelium-dependent vasodilator, acetylcholine (ACh), and an endothelium-independent vasodilator, nitroglycerin (NTG), were determined. In additional studies, the small intestine was isolated 5 or 20 h (hypodynamic sepsis) after CLP. Responses to ACh and NTG were determined in the isolated intestine. The results indicate that endothelium-dependent relaxation in both the aorta and superior mesenteric artery was depressed at 5 h after CLP. In contrast, there was no significant difference in the relaxation induced by NTG. Moreover, ACh-induced vascular relaxation in the isolated small intestine decreased at 5 and 20 h post-CLP without any significant alterations in NTG-induced relaxation. Since studies have shown that ACh-induced relaxation in the aorta is reduced at 20 h after CLP, it could be concluded that endothelium-derived NO release is depressed during hyperdynamic and hypodynamic stages of sepsis, not only in large arteries, but also at the microcirculatory level.
Cobalt exerts opposite effects on erythropoietin gene expression in rat hepatocytes in vivo and in vitro
Authors: Gopfert T. , Eckardt K. U. , Gess B. , Kurtz A.
Published: December 2017

This study investigates the effects of hypoxia and of cobalt on erythropoietin (EPO) gene expression in hepatocytes in vivo and in vitro in neonatal, juvenile, and adult rats. With the use of the ribonuclease protection assay to quantify RNA, both hypoxia (0.1% CO or 9% O2) and cobalt (60 mg/kg) elicit production of increased amounts of EPO mRNA in neonatal and juvenile rat liver in vivo. In vitro hepatocyte EPO gene expression could be reproducibly stimulated by hypoxia (3% O2) but not by cobaltous chloride (50-150 microM) within 2-20 h. Conversely, cobalt substantially attenuated the rise of EPO mRNA levels in response to hypoxia. This inhibitory effect of cobalt was mimicked by zinc but not by other metals. CO attenuated the rise of EPO mRNA levels in vitro in response to hypoxia; this inhibitory effect coincided with an inhibition of total RNA synthesis as determined by [3H]uridine incorporation. The lack of specific inhibitory effects of CO and of specific stimulatory effects of cobalt on hepatocyte EPO gene expression in vitro suggests that a specific heme oxygen sensor may be less important than in hepatoma cells.
Effects on breathing of medullary bicuculline microinjections in immature opossums
Authors: Farber J. P.
Published: December 2017

The role of medullary gamma-aminobutyric acid A (GABAA)-receptor activation in the expression of breathing was studied in suckling opossums (Didelphis virginiana) from 4 to 8 wk of age. Animals were anesthetized with a thiobarbiturate, and the ventral medulla was exposed so that drugs could be microinjected into the medulla with a two-barrel glass micropipette. The GABAA antagonist bicuculline at approximately 1-3 pmol total dose was injected in volumes < 1 nl; injections of saline with pontamine sky blue dye were used as controls and to mark location. Breathing pattern was assessed using diaphragm electromyography (EMG). Effective sites for bicuculline microinjection were obtained in the ventrolateral medulla, with both lateral reticular and inferior olive nuclei present as rostrocaudal markers. Responses among 18 tested animals included increased duration of breaths (Ttot) and duration of inspiration (Ti). Peak amplitude of the diaphragm EMG and peak amplitude of the diaphragm/Ti were not consistently affected. Transient apnea, lasting at least 8 s, occurred in five of the animals. Control solutions did not elicit respiratory responses. These results suggest that neural circuitry in the medulla, using the neurotransmitter GABA, can have an early role in the modulation of breathing pattern.
Lesions of area postrema attenuate but do not prevent anorectic action of peripheral serotonin in rats
Authors: Adipudi V. , Simansky K. J.
Published: December 2017

These studies assessed the effect of selectively ablating the area postrema (AP) on the action of peripheral serotonin [5-hydroxytryptamine (5-HT)] to reduce food intake in rats. Intraperitoneal 5-HT (0, 2.0, 4.0, and 8.0 mumol/kg) reduced the intakes of sweetened mash during a 30-min test in controls (APC) and in AP-lesioned rats (APX). The anorexia was dose dependent in controls but the dose-response function was flat after AP lesions. In another study, 2.0 mumol/kg 5-HT reduced intakes of both groups by approximately 25%, but AP lesions blunted the effect at 8.0 mumol/kg 5-HT (APX, -30% vs. APC, -85%). Behavioral analysis revealed that, compared with controls, AP lesions eliminated the decrease in frequency of feeding and reduced the incidence of resting and of an aberrant posture observed after 8.0 mumol/kg. Thus peripheral 5-HT decreases food intake in rats with AP lesions. Multiple mechanisms appear to be involved in the ability of peripheral 5-HT to reduce feeding. A high dose of 5-HT promotes responses associated with satiation but also produces behavioral toxicity; these effects involve the AP. Lower doses appear to engage processes that do not rely on the function of this circumventricular organ.
Effects of estrogen in vivo on coronary vascular resistance in perfused rabbit hearts
Authors: Gorodeski G. I. , Yang T. , Levy M. N. , Goldfarb J. , Utian W. H.
Published: December 2017

Estrogen or its vehicle was given daily to three groups of ovariectomized rabbits for various lengths of time, after which coronary flow was measured in their isolated perfused hearts. In one group, intramuscular injections of estrogen (40 micrograms/kg) for 7 or 14 days increased coronary flow by 40-50% (P < 0.05). In rabbits given estrogen intramuscularly for 7 days, the coronary flow returned to the basal level within 7 days after the estrogen injections were discontinued. In a second group of animals, intravenous injections of estrogen (10 micrograms/kg) for 4 days increased the coronary flow by 45% (P < 0.01). In a third group, we administered the estrogen transdermally for 4 days, and we measured the plasma estrogen levels at the end of this period. The coronary flow in this group was increased by 52% (P < 0.001), and the plasma estrogen levels ranged from 39 to 800 pg/ml. In all groups of experiments, the increments in coronary flow evoked by estrogen were virtually abolished by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase. We conclude that estrogen regulates coronary blood flow, in part by upregulating nitric oxide synthase in the coronary vasculature.