bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of fluid intake by carbohydrates: interaction between taste and calories
Authors: Ramirez I.
Published: December 2017

Rats were trained in an apparatus that infused water or nutritive fluids into their stomachs every time that they drank flavored fluids. Rats given saccharin to drink by mouth drank more fluid than rats given cherry-flavored water to drink. Furthermore, rats given saccharin to drink ingested much more fluid if they were given intragastric infusions of 6% carbohydrate than intragastric infusions of plain water. This stimulatory effect of carbohydrate infusion occurred within 1 or 2 days of training and was very large, amounting to > or = 70% increase in fluid intake compared with rats drinking saccharin and infused with water. On the other hand, infusions of 6% carbohydrate had no effect on the intake of rats given cherry-flavored water to drink. In an attempt to determine whether rats could be trained to respond to cherry flavor at all, rats were infused with a liquid diet whenever they drank cherry or saccharin-flavored water. When dry food was withheld, the rats learned to increase fluid intake so as to feed themselves. The rats given saccharin to drink acquired this task more readily than rats given cherry flavor to drink, but both groups took in normal amounts of food by the end of the 10-day training period. It is concluded that it is much easier to condition an increase in fluid intake with intragastric infusions of carbohydrate than with an arbitrary nonsweet flavor.
Body fat regulation after partial lipectomy in Siberian hamsters is photoperiod dependent and fat pad specific
Authors: Mauer M. M. , Bartness T. J.
Published: December 2017

Siberian hamsters exhibit seasonal fluctuations in body weight (fat). Initial exposure to a short photoperiod results in body fat loss that reverses after approximately 22 wk of short-day exposure. The purpose of this study was to determine whether Siberian hamsters are able to recover body fat after surgical reduction of total lipid stores and if so, whether this ability is photoperiod dependent and fat pad specific. Either the largest pair of internal fat pads, the epididymal white adipose tissue (EWAT) or one pair of two large external depots, the inguinal (IWAT) fat pads, were removed from male hamsters housed for 22 wk in a long (LD) or short (SD) photoperiod. Retroperitoneal fat pad (RWAT) mass was increased in LD EWAT- and IWAT-lipectomized hamsters. IWAT mass also was increased in the LD EWAT-lipectomized hamsters. Neither SD-lipectomized group compensated for body fat loss in any of the measured fat pads. Increased food intake was not necessary for total body fat recovery, but undereating partially may be responsible for the lack of recovery in SDs. The results of these experiments demonstrate a photoperiod-dependent ability of male Siberian hamsters to regulate total body fat after partial lipectomy. In addition, recovery involves a fat pad-specific compensatory response to partial lipectomy, rather than a general increase in lipid deposition in all fat depots.
Predominance of beta 3-adrenergic component in catecholamine activation of lipolysis in garden dormouse adipocytes
Authors: Carpene C. , Ambid L. , Lafontan M.
Published: December 2017

The beta 3-adrenoceptor (AR) agonists are potent activators of lipolysis in white adipose tissue. beta-AR agonists were tested here on the lipolytic activity of a hibernator, the garden dormouse (Eliomys quercinus L.). All the agonists exhibited full intrinsic activity; the most potent was the beta 3-AR agonist BRL-37344 [half-maximal effective concentration (EC50) = 0.8 nM]. The beta-antagonist idocyanopindolol (ICYP) also stimulated lipolysis of white adipocytes with the same potency and intrinsic activity as BRL-37344. The blockade of lipolytic effects of epinephrine or norepinephrine was similar to that of BRL-37344: the beta 1- and the beta 2-antagonists were quite ineffective. Total blockade occurred only with 100 microM bupranolol whatever the beta-agonist tested. This argues for the presence of a beta 3-component in the adrenergic-induced lipolysis. (-)-[125I]ICYP and (-)-[3H]CGP-12177 both labeled two populations of binding sites. On adipocyte membranes, binding of 0.6 nM (-)-[3H]CGP-12177 was inhibited with the following order of potency: isoproterenol > BRL-37344 > epinephrine. This order was modified at 20 nM, arguing for the beta-atypical nature of the low-affinity sites. Thus garden dormouse adipocytes possess beta 3-ARs, which are involved to an important degree in the adrenergic activation of lipolysis.
Chronic norepinephrine infusion stimulates glucose uptake in white and brown adipose tissues
Authors: Liu X. , Perusse F. , Bukowiecki L. J.
Published: December 2017

Cold exposure activates the sympathetic nervous system and markedly stimulates glucose uptake in rat peripheral tissues [A. L. Vallerand, F. Perusse, and L. J. Bukowiecki. Am. J. Physiol 259 (Regulatory Integrative Comp. Physiol. 28): R1043-R1049, 1990]. To test whether norepinephrine (NE) mimics the effects of cold exposure, we estimated the effects of chronic NE treatment on tissue glucose uptake by determining the glucose metabolic index using the 2-[1,2-3H(N)]deoxy-D-glucose method. NE was administered in conscious rats at various doses (ranging from 1.9 to 25.1 nmol.kg-1.min-1) during 4 days via minipumps implanted subcutaneously. At doses > 10 nmol.kg-1.min-1, NE maximally stimulated glucose uptake in interscapular brown adipose tissue (approximately 50 times above controls) and epididymal white adipose tissue (approximately 3 times above controls). NE infusion (18.8 nmol.kg-1.min-1) increased the circulating levels of NE from 1.1 +/- 0.1 to 19.2 +/- 0.4 nM (P < 0.001), which is in the range of concentrations for the stimulatory effects of NE on glucose uptake in isolated brown adipocytes. At all concentrations tested, NE infusion did not stimulate glucose uptake in the heart and skeletal muscles. NE treatment did not significantly alter plasma insulin or glucose levels but increased the concentration of circulating free fatty acids. The capacity of brown adipose tissue for NE stimulation of glucose uptake (expressed per g of tissue) was much higher than that of white adipose tissue (100 times), various types of white or red skeletal muscles (10-80 times), or the heart (3-4 times).(ABSTRACT TRUNCATED AT 250 WORDS)
Clearance receptor-mediated control of atrial natriuretic factor in experimental congestive heart failure
Authors: Brandt R. R. , Redfield M. M. , Aarhus L. L. , Lewicki J. A. , Burnett J. C.
Published: December 2017

Circulating atrial natriuretic factor (ANF) is regulated by clearance receptors (ANFR-C). C-ANF-(4-23) is a ring-deleted analogue of ANF, which binds specifically to ANFR-C. The present studies were undertaken to determine total metabolic (TMCR), pulmonary (PCR), and renal clearance rates (RCR) of ANF in a group of seven mongrel dogs in chronic congestive heart failure (CHF) in comparison with a control group (n = 6). TMCR was not altered in CHF [1,534 +/- 319 vs. control: 1,735 +/- 208 ml/min; P = not significant (NS)] in association with an elevation of circulating endogenous ANF (206 +/- 44 vs. control: 36 +/- 10 pg/ml; P < 0.01). Infusion of C-ANF-(4-23) reduced TMCR in both groups similarly (CHF: 753 +/- 134 vs. control: 972 +/- 156 ml/min; P = NS). PCR was lower in CHF (286 +/- 431 vs. 1,672 +/- 407 ml/min; P < 0.05), whereas RCR was not different (10 +/- 24 vs. control: 15 +/- 25 ml/min; P = NS). ANFR-C blockade did not facilitate urinary sodium excretion in CHF. These studies demonstrate that 1) TMCR does not contribute to elevated endogenous ANF in CHF; 2) total functional activity of the clearance receptor pathway is preserved in CHF; and 3) renal ANF metabolism and the clearance receptor pathway are not linked to the avid sodium retention and renal ANF resistance observed in chronic CHF.
Changes in plasma glutathione concentrations, turnover, and disposal in developing rats
Authors: Ookhtens M. , Mittur A. V. , Erhart N. A.
Published: December 2017

We have previously shown that sinusoidal reduced glutathione (GSH) efflux declines during development because of a declining maximum transport rate [Am. J. Physiol. 261 (Gastrointest. Liver Physiol. 24): G648-G656, 1991]. Because rat liver serves as the principal source of plasma GSH, we studied the response of plasma GSH to this declining inflow from liver. In immature (28- to 42-day) and mature (90- to 151-day) rats we injected tracer boluses of [35S]GSH intravenously and collected arterial samples over a 0.75- to 8-min interval while plasma GSH pool remained at steady state. Concentrations and radioactivities of GSH, oxidized glutathione (GSSG), cysteine (CYSH), cystine (CYSS), and cysteine-glutathione disulfides (CYSSG) and the radio-activities of proteins were measured in plasma. Our results show the following changes in plasma concentrations (microM): decreases in unbound (free) GSH (26.0 +/- 2.1 to 12.4 +/- 0.98; P < 0.001), total unbound GSH equivalents GSH + 2GSSG (29.1 +/- 2.1 to 15.3 +/- 1.2; P < 0.001), total reducible (unbound + bound) GSH (39.3 +/- 2.2 to 28.9 +/- 2.6; P < 0.025), and free CYSH (57.6 +/- 8.5 to 29.9 +/- 4.0; P < 0.05); no changes in GSSG (1.57 +/- 0.27 vs. 1.47 +/- 0.41), CYSS (36.7 +/- 12 vs. 43.4 +/- 17), and total unbound CYSH equivalents CYSH + 2CYSS (131 +/- 15 vs. 117 +/- 18); increases in total reducible (unbound + bound) CYSH (158 +/- 8.1 to 203 +/- 24; P < 0.05) and CYSSG (1.80 +/- 0.42 to 4.94 +/- 1.4 in microM GSH equivalents; P < 0.05). A concurrent decline occurred in irreversible disposal rate (IDR) of plasma GSH from 38.5 +/- 4.9 to 16.4 +/- 1.4 nmol.min-1.ml-1 (P < 0.001) as determined by compartmental analysis of tracer data. This 57% decrease in IDR parallels a decrease of 53% in the inflow of GSH estimated by perfused livers (17.0 to 8.0 nmol.min-1.ml plasma-1). However, perfused liver estimates do not match > 44-49% of plasma IDR. Thus perfused liver appears to underestimate the true rate of sinusoidal GSH efflux taking place in vivo. Some earlier arteriovenous data and our present portal vein-to-hepatic vein difference measurements appear to corroborate this view.
Fos expression in ferret dorsal vagal complex after peripheral emetic stimuli
Authors: Boissonade F. M. , Sharkey K. A. , Davison J. S.
Published: December 2017

The aim of this study was to investigate neuronal activation in the dorsal vagal complex of the halothane-anesthetized ferret after peripheral emetic stimuli. Neuronal activity was studied by examining the distribution of the nuclear phosphoprotein Fos using immunohistochemistry. The emetic stimuli used were electrical stimulation of the supradiaphragmatic vagal communicating branch (SVCB) or intraduodenal injection of hypertonic saline. Electrical stimulation of the SVCB induced the densest Fos expression within the medial subnucleus of the nucleus of the solitary tract. After hypertonic saline injection, the greatest density of Fos-positive nuclei was observed within the area postrema and also in the medial subnucleus of the nucleus of the solitary tract. It was concluded that the emetic response to hypertonic saline involves neurons in both the area postrema and the nucleus of the solitary tract, especially the medial subnucleus, and that the medial subnucleus is important in the emetic response to SVCB stimulation.
Cardiovascular effects of human recombinant interleukin-1 beta in conscious rats
Authors: Bataillard A. , Sassard J.
Published: December 2017

Cardiovascular effects of human recombinant interleukin-1 beta (hrIL-1 beta) were investigated in normotensive rats using a computerized analysis of arterial blood pressure in conscious, unrestrained animals. Intravenous injection of hrIL-1 beta induced a rapid and short-lasting rise in blood pressure associated with a first slight tachycardia followed by a second sustained and pronounced increase in heart rate. These effects occurred in a dose-related manner. Pretreatment with a converting-enzyme inhibitor (perindopril) did not modify the hrIL-1 beta-induced increase in blood pressure. Blockade of beta 1-adrenoceptors (atenolol) prevented the tachycardia, but did not significantly affect the pressor response to hrIL-1 beta. On the contrary, the hrIL-1 beta-induced increase in blood pressure was inhibited by an alpha 1-adrenoceptor antagonist (prazosin), whereas the tachycardia was untouched. Finally, pretreatment with a cyclooxygenase inhibitor (indomethacin) completely abolished the cardiovascular response to hrIL-1 beta. These results suggest that the hrIL-1 beta-induced pressor response and associated tachycardia require the synthesis of prostaglandins and involve a sympathetic nervous system activation but do not depend on the renin-angiotensin system.
Specificity of the imino acid carrier in rat small intestine
Authors: Munck B. G. , Munck L. K. , Rasmussen S. N. , Polache A.
Published: December 2017

The rat intestinal imino acid carrier is chloride independent, while in guinea pig and rabbit intestine it is chloride dependent. While non-alpha-amino acids do not significantly interact with guinea pig and rabbit imino acid carriers, inhibition studies had indicated that in rat small intestine beta-alanine, gamma-aminobutyric acid (GABA), and probably taurine might be transported by the imino acid carrier. The present study of rat jejunum demonstrates that the half-maximal activation concentration of beta-alanine (K1/2 beta-Ala) is identical to its inhibition constant (Ki beta-Ala) against GABA, that K1/2GABA is identical to KiGABA against beta-alanine, that proline and sarcosine have identical values of Ki against beta-alanine and GABA, and that Ki of beta-alanine and proline against sarcosine are equal to their K1/2 values. Taurine inhibits the transport of beta-alanine, and 300 mM proline and beta-alanine reduce the transport of taurine measured at 80 mM taurine to the level expected for the diffusive contribution, corresponding to Ki values equal to those against sarcosine. Thus the rat imino acid carrier is the principal carrier of taurine and the only carrier of beta-alanine and GABA. It is also demonstrated that alpha-amino-monocarboxylic acids with side chains in excess of one methyl group do not significantly interact with the imino acid carrier, and the lack of stereospecificity is confirmed.
Autonomic functions and orthostatic responses 24 h after acute intense exercise in paraplegic subjects
Authors: Engelke K. A. , Shea J. D. , Doerr D. F. , Convertino V. A.
Published: December 2017

We tested the hypothesis that a bout of graded exercise designed to elicit maximal effort would increase the sensitivity of autonomically mediated baroreflexes and enhance blood pressure (BP) stability in subjects prone to postural hypotension. Therefore, we measured heart rate (HR), BP, forearm vascular resistance (FVR), and vasoactive hormone responses before and during 15 min of 70 degrees head-up tilt (HUT) in 10 paraplegic subjects (21-65 yr) on two occasions: 1) 24 h after maximal arm-crank exercise (postexercise) and 2) without exercise (control). During HUT, HR increased 30 beats/min in both postexercise and control, but the reduction in systolic BP (SBP) during control (-12.0 +/- 4.6 mmHg) was larger (P = 0.017) than that during HUT after exercise (-0.3 +/- 4.3 mmHg). The postexercise increase in FVR from supine to HUT of 17.0 +/- 2.4 to 24.8 +/- 3.2 peripheral resistance units (PRU) was greater (P = 0.042) than the increase observed during control (18.3 +/- 3.7 to 19.5 +/- 3.1 PRU). The gain of the carotid-cardiac baroreflex was also increased (P = 0.049) after exercise. Responses in norepinephrine, vasopressin, and plasma renin-angiotensin induced by HUT were similar for control and postexercise, and there was no difference in either leg compliance or plasma volume between the two conditions. Additionally, HR and SBP responses to phases II and IV of the Valsalva maneuver, indexes of integrated baroreflex sensitivity, were increased (P < 0.05) after maximal exercise compared with control. Thus acute intense exercise eliminated orthostatic hypotension in paraplegics, was associated with increased FVR and baroreflex sensitivity, and was independent of blood volume changes.
Renal, endocrine, and hemodynamic interactions of atrial and brain natriuretic peptides in normal men
Authors: Florkowski C. M. , Richards A. M. , Espiner E. A. , Yandle T. G. , Frampton C.
Published: December 2017

Brain natriuretic peptide (BNP) is a recently identified hormone that is secreted by the human heart and circulates in plasma with natriuretic, endocrine, and hemodynamic effects similar to those of atrial natriuretic peptide (ANP). To examine the interaction of human BNP with ANP, we studied eight normal men receiving constant infusions of ANP (2.0 pmol.kg-1.min-1 for 5 h), with and without superimposed infusions of BNP (2.0 pmol.kg-1.min-1 for 2 h), using a balanced random-order design. BNP infusions achieved plasma levels of 30-35 pmol/l at 90-120 min and were similar to levels observed in mild heart failure. Metabolic clearance rate of BNP (mean 4.6 +/- 0.4 l/min) and disappearance rate from plasma (t1/2 18.9 min) were similar to values determined previously in the absence of exogenous ANP. In contrast, the addition of BNP induced a progressive and reversible increase (50%) in steady-state plasma ANP. Compared with ANP alone, BNP induced an additional (50%) increase in sodium excretion (P < 0.05) and significant increases in both plasma (P < 0.001) and urine guanosine 3',5'-cyclic monophosphate (P < 0.01). Systolic blood pressure was lowered by the addition of BNP (P < 0.01) and continued to fall after cessation of BNP infusions. Despite this, the response of the renin-aldosterone and sympathetic nervous systems (heart rate and plasma catecholamines) was not significantly different on the two study days. As well as showing additive effects of the two natriuretic peptides, these studies point to important interactions of BNP on ANP metabolism at plasma levels observed in mild heart failure.
Mechanisms of hypertension in transgenic rats expressing the mouse Ren-2 gene
Authors: Moriguchi A. , Brosnihan K. B. , Kumagai H. , Ganten D. , Ferrario C. M.
Published: December 2017

Transgenic (TG) rats carrying the mouse Ren-2 gene (Ren-2d)27 are a newly established monogenetic model in hypertension research. To gain an insight into the mechanisms of this form of hypertension we determined the effects of a 13-day therapy with losartan (10 mg/kg) or lisinopril (20 mg/kg) on the blood pressure (BP) and plasma levels of angiotensin (ANG) peptides of mature female TG hypertensive and Sprague-Dawley (SD) rats. The contribution of endothelium-derived nitric oxide (NO) to the maintenance of their hypertension and the response to therapy was evaluated by systemic injection of either NG-monomethyl-L-arginine (L-NMMA) or endothelin-1. Hypertension in TG rats was associated with decreased plasma ANG I, no differences in plasma ANG II, and plasma ANG-(1-7) near the detectable level. Lisinopril lowered BP more than losartan in both TG hypertensive and normotensive controls. In both strains, the chronic fall in BP produced by lisinopril was accompanied by significant increases in plasma ANG I and ANG-(1-7), while losartan augmented plasma ANG I and ANG II in both strains and plasma ANG-(1-7) in TG rats. Inhibition of NO synthase reversed the fall in BP produced by either lisinopril or losartan in SD controls. In contrast, administration of L-NMMA to TG rats given the same therapy did not. The transient endothelium-mediated relaxing phase of the depressor response to systemic injections of endothelin-1 was attenuated by losartan and lisinopril in TG rats. These studies indicate that hypertension in female TG rats is mediated by the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurotransmitters in the parabrachial nucleus mediating visceral input to the thalamus in rats
Authors: Saleh T. M. , Cechetto D. F.
Published: December 2017

The putative neurotransmitters in ascending visceral pathways were investigated by recording changes in the response of thalamic neuronal activity evoked by vagal stimulation before and after neurotransmitter antagonist injections into the parabrachial nucleus (PB). Male Wistar rats (n = 39) were anesthetized with chloral hydrate and alpha-chloralose, ventilated, and blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated to elicit changes in single and multiunit activity in the visceral thalamus. Peristimulus-time histograms of thalamic activity were made before and after 200-nl injections of antagonist or control solution into the PB. Synaptic blockade using cobalt (10 mM) injections into the PB inhibited both the thalamic response evoked by vagal stimulation (86-100%) and the spontaneous firing of thalamic neurons (88-92%). Injections of kynurenate (250 mM) or the N-methyl-D-aspartate (NMDA) antagonist, DL-2-amino-5-phosphonopentanoic acid (AP-5; 200 microM), inhibited (87-94% and 92-100%) the thalamic neuronal response evoked by vagal stimulation. The alpha-adrenergic antagonist, phentolamine (0.1 microM), or the specific alpha 2-adrenergic antagonist, yohimbine (0.1 microM), inhibited the spontaneous firing of thalamic units (42-56% and 64-77%) but had no effect on the vagally evoked response. Bicuculline [gamma-aminobutyric acid (GABA) A-subtype antagonist] significantly enhanced spontaneous thalamic neuronal activity (108-125%) without effect on the vagally evoked response. Atropine (0.1 microM) had no significant effect on either the vagally evoked response or the spontaneous firing of thalamic neurons. These results suggest that the relay of visceral afferent sensory information through the PB is mediated by NMDA receptors and that alpha 2 and GABAA receptors contribute to the tonic activity of ventral basal thalamic neurons receiving visceral input.
Lack of edema in toad lungs after pulmonary hypertension
Authors: Smits A. W.
Published: December 2017

Pulmonary hypertension and hyperperfusion were experimentally induced in conscious toads (Bufo marinus) to test whether excessive transcapillary filtration might result in pulmonary edema. Elimination of pulmocutaneous baroreceptor afferent input by bilateral sectioning of recurrent laryngeal nerves caused mean pulmonary arterial pressure to increase by nearly 25 mmHg and pulmonary blood flow to increase fourfold. Left lungs of control (normotensive) and hypertensive toads were isolated by snares at the hilus and excised for compartmental lung fluid analysis. Total lung water was significantly elevated in hypertensive toads (8.44 +/- 0.30 ml/g dry mass) compared with control animals (7.15 +/- 0.22 ml/g dry mass), but this increase was apparently not due to an accumulation of transcapillary filtrate (extravascular fluid volumes = 4.57 +/- 0.21 and 4.35 +/- 0.17 ml/g dry mass, respectively). Instead, significant increases in pulmonary intravascular fluid volume accounted for 83% of the increase in total lung water. Such absence of pulmonary edema under these extreme cardiovascular states suggests that mobilization of pulmonary lymph is unusually effective in these animals.
Effects of temperature and freezing on hepatocytes isolated from a freeze-tolerant frog
Authors: Storey K. B. , Mommsen T. P.
Published: December 2017

Metabolically active hepatocytes prepared from freeze-tolerant wood frogs, Rana sylvatica, were used to examine the direct effects of temperature and freezing on cryoprotectant synthesis and to assess the effectiveness of the natural cryoprotectant glucose in the freezing preservation of the isolated cells. Freshly isolated hepatocytes showed slow leakage of lactate dehydrogenase, readily synthesized urea, and oxidized a variety of 14C-labeled substrates. Effects of temperature on glucose production by isolated hepatocytes showed a normal Arrhenius relationship. However, compared with 0 degrees C control cells, either incubation at higher temperatures or freezing at -3 degrees C reduced the activity of glycogen phosphorylase alpha. These data suggest that the freezing-induced cryoprotectant production that occurs in vivo is not due to direct action of either low temperature or freezing on liver cell metabolism. The natural cryoprotectant glucose was also an excellent cryoprotectant of hepatocytes in vitro. In the absence of glucose, freezing caused a substantial leakage of lactate dehydrogenase from isolated hepatocytes, the rate of leakage increasing as freezing temperature decreased. Addition of 200-600 mM glucose to the incubation medium (similar to natural levels) fully protected cells against damage during freezing at -4 or -8 degrees C, normal freezing temperatures experienced by these frogs. Glucose also greatly improved freezing survival of isolated frog hepatocytes at ultralow temperatures (-80 or -196 degrees C).
Prostaglandin H2-thromboxane A2 and renal functions in the Lyon hypertensive rat
Authors: Liu K. L. , Benzoni D. , Sassard J.
Published: December 2017

The influence of renal perfusion pressure (RPP) on renal functions was studied in anesthetized 8-wk-old Lyon hypertensive (LH) and normotensive (LN) rats before and after a specific blockade of prostaglandin (PG) H2-thromboxane (Tx) A2 receptors using GR-32191B. The nervous and hormonal influences on the kidneys were controlled by renal denervation, adrenalectomy, and an infusion of norepinephrine, aldosterone, hydrocortisone, and vasopressin. With the use of inflatable cuffs, RPP was varied from 100 to 125 and then to 150 mmHg. In control conditions, the renal blood flow (RBF) and glomerular filtration rate (GFR) were independent of RPP in both strains. LH kidneys differed from LN controls by an increased preglomerular vasoconstriction as indicated by a similar decrease in RBF and GFR. Moreover, the pressure-natriuresis curve was blunted in LH compared with LN kidneys. GR-32191B did not affect the renal function of LN rats. In LH kidneys, it normalized RBF and renal vascular resistance and improved GFR, whereas it had no effect on the pressure-natriuretic relationship. It is concluded that the elevated preglomerular vascular resistance that characterizes LH rats is dependent on an overstimulation of PGH2-TxA2 receptors whereas these latter are not involved in the control of pressure-natriuresis.
Temporal analysis of the anti-inflammatory effects of decentralization of the rat superior cervical ganglia
Authors: Mathison R. , Carter L. , Mowat C. , Bissonnette E. , Davison J. S. , Befus A. D.
Published: December 2017

Bilateral decentralization of the superior cervical ganglia (SCG) reduced the pulmonary inflammation that develops 4-8 h after induction of anaphylaxis in Nippostrongylus brasiliensis-sensitized rats. Histamine levels in peritoneal lavage fluid and rat mast cell protease type II in serum were increased to comparable levels in sham-operated and decentralized rats. In vitro stimulation of alveolar macrophages (ALM) with lipopolysaccharide (LPS) provoked tumor necrosis factor-alpha (TNF-alpha) release that was two to three times greater with unchallenged decentralized rats than with sham-operated rats. However, after allergen challenge LPS-stimulated TNF-alpha release from ALM of sham-operated rats increased threefold and lasted at least 24 h, whereas with decentralized rats release of this cytokine actually decreased at 4 and 8 h. The increase in the phagocytosis and respiratory burst of circulating neutrophils seen at 4 and 8 h after allergen challenge in sham-operated rats was reduced significantly by decentralization. These results suggest that the attenuation of anaphylaxis-induced pulmonary inflammation that occurs with decentralization of the SCG is primarily associated with downregulation of neutrophil and macrophage functions.
On determinants of glomerular filtration rate after inhibition of proximal tubular reabsorption
Authors: Leyssac P. P. , Karlsen F. M. , Holstein-Rathlou N. H. , Skott O.
Published: December 2017

The carbonic anhydrase inhibitor acetazolamide (ACZ) inhibits the absolute rate of proximal reabsorption (APR), causes a reduction in glomerular filtration rate (GFR), and activates the tubuloglomerular feedback mechanism (TGF) resulting in afferent vasoconstriction. The quantitative importance of the afferent vasoconstriction for the reduced GFR was tested by addition of a vasodilator during continuous infusion of ACZ. Dopamine caused an increase in renal blood flow (RBF) to pre-ACZ levels. Glomerular capillary pressure (Pgc) and proximal tubular pressure (Pprox) increased in parallel (by 3.1 and 3.0 mmHg, respectively) leaving pressure gradient (delta P) unchanged. APR, as estimated from the clearances of 51Cr-EDTA and lithium, remained unchanged. Urine flow almost doubled. GFR was only modestly reversed (pre-ACZ/ACZ/ACZ+dopamine: 100/77/83%). It is concluded that relieving the afferent vasoconstriction seen after carbonic anhydrase inhibition fails to restore GFR to its control value. This is due to the high flow resistance in the distal nephron segments during the increased tubular flow rates seen after ACZ. The high distal flow resistance causes a parallel change in Pgc and Pprox and thus leaves delta P nearly unchanged. The present study highlights the importance of the distal flow resistance in determining delta P and therefore GFR during conditions where tubular flow rate is increased.
Neuropeptides in the Australian lungfish Neoceratodus forsteri: effects in vivo and presence in autonomic nerves
Authors: Holmgren S. , Fritsche R. , Karila P. , Gibbins I. , Axelsson M. , Franklin C. , Grigg G. , Nilsson S.
Published: December 2017

The Australian lungfish Neoceratodus forsteri is one of the few extant species of a phylogenetically ancient group. Immunohistochemistry showed the presence of galanin-, vasoactive intestinal polypeptide (VIP)-, neurotensin-, substance P-, and calcitonin gene-related peptide (CGRP)-like immunoreactivities in nerve fibers in the heart, lung, and gut, with a coexistence of VIP-, galanin-, and somatostatin-like immunoreactivity in the lung and galanin- and somatostatin-like immunoreactivity in the gut. About 20% of the substance P-immunoreactive fibers in gut and lung contained CGRP-like material. Major vessels showed a sparse innervation. In free-swimming unanesthetized fish, neurotensin (1 nmol/kg), galanin (1 nmol/kg), and bombesin (10 nmol/kg) reduced the heart rate. In two specimens tested, the effect of neurotensin was partially antagonized by atropine. Galanin and bombesin reduced and cholecystokinin 8 (CCK-8-S) increased blood flow to the lung. Neurotensin decreased, CCK-8-S increased, and substance P had no effect on dorsal aortic pressure, and all three decreased flow to the gut. It can be concluded from the present study that the general vertebrate pattern of cardiovascular and visceral nervous control by several neuropeptides is present also in Neoceratodus.
Angiotensin II overflow from canine skeletal muscle in vivo: importance of plasma angiotensin I
Authors: Schwieler J. H. , Nussberger J. , Kahan T. , Hjemdahl P.
Published: December 2017

The overflows (i.e., veno-arterial concentration differences multiplied by plasma flow) of angiotensin-(1-10) decapeptide (ANG I) and angiotensin-(1-8) octapeptide (ANG II) from blood-perfused canine gracilis muscle in situ were studied. Special precautions were taken to minimized ex vivo generation and/or degradation of angiotensins in the sampled blood. ANG I was found to be generated in the catheter system supplying the gracilis muscle with arterial blood, but plasma renin activity and ANG II levels were uninfluenced by the catheter system. A positive venoarterial concentration difference over the muscle itself was found for ANG II but not for ANG I under basal conditions. Isoprenaline elicited vasodilatation, reduced ANG I overflow, and tended to increase ANG II overflow, whereas beta-adrenoceptor blockade by propranolol had no effect on these variables. In conclusion, we found no evidence for a local de novo synthesis of ANG II from the gracilis muscle vasculature in vivo. The net overflow of ANG II was most likely caused by local conversion in the tissue of ANG I artifactually generated in the arterial catheter system. beta-Adrenoceptor stimulation enhanced the local conversion of ANG I to ANG II, probably by exposing a greater endothelial surface containing angiotensin-converting enzyme activity.
Chemokines/intercrines and central regulation of feeding
Authors: Plata-Salaman C. R. , Borkoski J. P.
Published: December 2017

Chemokines/intercrines are structurally and functionally related cytokines that induce specific actions on the immune system and are released in response to infection, inflammation, and trauma. These pathological processes are frequently accompanied with food intake suppression. In the present study, the action of chemokines/intercrines on the regulation of feeding was investigated using the intracerebroventricular microinfusion of chemokine/intercrine-alpha subfamily members [interleukin-8 (IL-8); growth-related cytokine/melanoma growth-stimulating activity (GRO-alpha/MGSA); platelet factor-4 (PF-4); beta-thromboglobulin (beta-TG); and interferon-inducible protein-10 (IP-10)] and beta-subfamily members [monocyte chemotactic protein-1/monocyte chemotactic and activating factor (MCP-1/MCAF); regulated upon activation normal T-cell expressed and presumably secreted (RANTES); macrophage inflammatory protein-1 alpha (MIP-1 alpha); and macrophage inflammatory protein-1 beta (MIP-1 beta)]. The doses administered were 1.0, 20, and 100 ng/rat of the chemokine/intercrine. The intracerebroventricular administration of three members of the alpha-subfamily (IL-8, PF-4, and IP-10) and two members of the beta-subfamily (MCP-1/MCAF and RANTES) decreased the short-term (2-h) food intake. These effective chemokines/intercrines, however, were significantly less potent than IL-1 beta in decreasing feeding. The results support the hypothesis that only a subset of immunomodulators released during pathological processes may participate in the regulation of feeding with different potencies.
Growth and metabolism of gastrointestinal and skeletal muscle tissues in protein-malnourished neonatal pigs
Authors: Ebner S. , Schoknecht P. , Reeds P. , Burrin D.
Published: December 2017

Our objective was to determine whether neonates adapt to protein malnutrition by preserving the relative growth and metabolism of gastrointestinal tissue at the expense of skeletal muscle. We measured gastrointestinal, liver, and carcass tissue masses and blood flow, oxygen consumption, and net glucose and amino acid fluxes in vivo of the portal-drained visceral tissues (PDV) in neonatal pigs fed isocaloric diets containing either 30% protein [control (C)] or 15% [low protein (LP)] for 14 days. Relative protein mass and fasting blood flow and oxygen consumption of PDV tissue in either group were not different. Relative protein mass of liver and carcass was lower in LP pigs. Net essential amino acid absorption and insulin concentration after feeding were lower in LP pigs. Results demonstrate that protein malnutrition in neonatal pigs differentially altered rates of tissue growth, such that the proportion of body protein partitioned into gastrointestinal tissue was preserved, while that of skeletal muscle was reduced. Chronic reduction in amino acid absorption in protein-malnourished pigs resulted in a reduced insulin response to feeding, which presumably limited substrate availability and the anabolic stimulus for skeletal muscle protein accretion.
Loss of osmotic thirst in multiple system atrophy: association with sinoaortic baroreceptor deafferentation
Authors: Bevilacqua M. , Norbiato G. , Righini V. , Vago T. , Castelli L. , Carella F. , Caraceni T.
Published: December 2017

We evaluated plasma osmolality (pOsm), thirst, and vasopressin response to hypertonic saline infusion in 14 patients with multiple system atrophy (MSA). This disease is characterized by the degeneration of noradrenergic neurons in the central nervous system and severe orthostatic hypotension. Seven patients were also characterized by the lack of vasopressin response to hypotension (group B) and seven by a preserved response (group A). In group A pOsm rose from 290 +/- 2 to 312 +/- 6 mosmol/kgH2O, vasopressin from 0.9 +/- 0.3 to 5.7 +/- 0.5 pmol/l, and thirst from 1.1 +/- 0.1 to 8.7 +/- 1.1 cm on the visual analog scale. After saline, patients drank 1,215 +/- 150 ml of water (no different from healthy controls). In group B patients' pOsm rose from 296 +/- 3 to 325 +/- 6 mosmol/kgH2O and vasopressin from 1.2 +/- 0.1 to 19.6 +/- 0.4 pmol/l (P < 0.01 vs. group A and controls). Group B patients had no thirst during saline and drank little after the challenge (175 +/- 50 ml; P < 0.01 vs. group A and control). Forced drinking decreased vasopressin in patients before changes in pOsm, showing that inhibitory afferents from oropharyngeal mucosa were intact. In MSA patients with altered afferent control of vasopressin there is a dissociation between the osmotic control of thirst and the osmotic control of vasopressin.
Neuropeptide Y in hypothalamic paraventricular nucleus: a center coordinating energy metabolism
Authors: Billington C. J. , Briggs J. E. , Harker S. , Grace M. , Levine A. S.
Published: December 2017

Intracerebroventricular injection of neuropeptide Y (NPY) has two effects on energy metabolism in addition to increased feeding: decreased brown fat thermogenesis and increased white fat lipoprotein lipase (LPL) enzymatic activity. We hypothesized that the paraventricular nucleus (PVN) of the hypothalamus is the controlling neural site for these responses. We further hypothesized that NPY stimulation at PVN would reduce gene expression for the critical brown fat thermogenic protein, uncoupling protein (UCP), and increase gene expression for the key white fat storage enzyme, LPL. In the first experiment, three groups of rats received injections every 6 h for 24 h (5 injections total) into the PVN:1) NPY (1 micrograms/1 microliters injection) and ad libitum food; 2) NPY (1 micrograms/1 microliters injection) and food restricted to control intake; 3) saline injection (1 microliter) and ad libitum food. Both NPY-treated groups showed significant reductions (P < 0.05) in brown fat UCP mRNA levels and marked stimulation of LPL mRNA levels relative to controls. In the second experiment, four groups of seven rats had NPY injected into the PVN:0 (vehicle control); 0.1 microgram; 0.5 microgram; and 1 microgram. Injections were made every 6 h for 24 h. There was a dose-related reduction in UCP mRNA produced by the NPY treatment. NPY treatment increased LPL mRNA, but a smooth dosing effect was not evident. The observation that NPY in the PVN can coordinate more than one component of energy metabolism is significant when considered with many reports of responsiveness of NPY activity in the arcuate nucleus-PVN neural circuit to perturbations of energy balance such as fasting and feeding, diabetes, and genetic obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
Peripheral naloxone attenuates lipopolysaccharide fever in guinea pigs by an action outside the blood-brain barrier
Authors: Romanovsky A. A. , Shido O. , Ungar A. L. , Blatteis C. M.
Published: December 2017

We have previously shown that the febrile response of guinea pigs to lipopolysaccharide (LPS) is attenuated by the subcutaneous administration of the tertiary mu-receptor opioid antagonist naloxone-hydrochloride (Nal-HCl). Because Nal-HCl readily crosses the blood-brain barrier (BBB), this study was undertaken to investigate whether its effect on fever is mediated peripherally or centrally. For this, the effects of 1) Nal-HCl (23 and 46 mumol/kg sc), 2) the quaternary opioid antagonists Nal-methiodide (Nal-mI, 46 and 92 mumol/kg sc) and Nal-methobromide (Nal-mBr, 92 mumol/kg sc), which do not cross the BBB, and 3) intracerebroventricular Nal-HCl (0.25 and 1.25 mumol) on the febrile response to intravenous S. enteritidis LPS (2 micrograms/kg) were investigated in conscious guinea pigs. Under afebrile conditions, both Nal-HCl (whether administered sc or icv) and its quaternary analogues induced hypothermic responses. Peripheral Nal-HCl, Nal-mI, and Nal-mBr also attenuated both phases of the characteristically biphasic LPS fever. The thermal effects of the peripheral opioid antagonists, both tertiary and quaternary, were associated with cutaneous vasodilation. Intracerebroventricularly administered Nal-HCl did not evoke any attenuation of fever. The analysis of the data shows that Nal-HCl possesses three different thermoregulatory actions: a central hypothermic action, a peripheral thermolytic action (which is due to, at least partly, cutaneous vasodilation), and a peripheral antipyretic action. The latter effect suggests that, in guinea pigs, circulating opioids may have a role in fever production.
Angiotensin I is converted to angiotensin II by a serine protease in human detrusor smooth muscle
Authors: Lindberg B. F. , Nilsson L. G. , Hedlund H. , Stahl M. , Andersson K. E.
Published: December 2017

The aim of the present study was to investigate whether a pathway for conversion of angiotensin I (ANG I) to angiotensin II (ANG II) other than that via angiotensin-converting enzyme (ACE) is present in the smooth muscle of the human detrusor. Isolated detrusor strips from 11 patients were contracted by ANG I (1 microM) in the absence or presence of enalaprilat (10 microM), soybean trypsin inhibitor (STI, 200 micrograms/ml), or both. The metabolic activity in detrusor membranes from four patients was studied separately using Hip-Gly-Gly or ANG I as a substrate, with or without various protease inhibitors. The contractile response to ANG I (1 microM) was depressed by enalaprilat from 66 +/- 22 (mean +/- SD) to 39 +/- 13% of the K+ (124 mM)-induced response (P < 0.01, n = 11), and the combination of enalaprilat and STI resulted in a further reduction in contractile amplitude to 25 +/- 14% (P < 0.01 vs. K+, and P < 0.05 vs. enalaprilat alone) and a significantly slower developing contraction with a time to peak of 3.7 +/- 1.7 vs. 1.1 +/- 0.3 min for ANG I alone (P < 0.01). In detrusor membranes, a low ACE activity, inhibitable by captopril, was demonstrated by the formation of hippuric acid (0.70 nmol.min-1.mg protein-1) from the synthetic ACE substrate, Hip-Gly-Gly. However, the conversion of ANG I (166 nmol.min-1.mg protein-1) to ANG II was not affected by ACE inhibition, while serine protease inhibitors, e.g., STI and chymostatin, completely prevented ANG II formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Circadian thermosensitive characteristics of suprachiasmatic neurons in vitro
Authors: Derambure P. S. , Boulant J. A.
Published: December 2017

The circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) affects several regulatory systems, including body temperature. To study circadian changes in the firing rate and thermosensitivity of SCN neurons, single-unit activity was recorded from the dorsomedial and ventrolateral SCN in frontal slices of rat hypothalamus during changes in tissue temperature. When analyzed according to circadian time (CT), 305 neurons were characterized by firing rate and 208 neurons were characterized by thermosensitivity. Circadian firing-rate changes were evident only in the dorsomedial SCN, with peak firing rates occurring during the subjective day. Circadian changes in SCN neuronal thermosensitivity also were observed, but the greatest thermosensitivity occurred during the subjective night. Increased thermosensitivity was most dramatic in the ventrolateral SCN, where > 40% of the neurons were warm sensitive in the CT 16- to 20-h period. These changes in neuronal thermosensitivity may reflect interactions between body temperature and circadian rhythms.
Interaction between chemoreceptor and stretch receptor inputs at medullary respiratory neurons
Authors: Bajic J. , Zuperku E. J. , Tonkovic-Capin M. , Hopp F. A.
Published: December 2017

The interaction between afferent inputs from carotid body chemoreceptors (CCRs) and from slowly adapting pulmonary stretch receptors (PSRs) on the discharge patterns of medullary inspiratory (I) and expiratory (E) neurons was characterized in thiopental sodium-anesthetized, paralyzed, ventilated dogs. A cycle-triggered ventilator was used to produce control and test pulmonary afferent input patterns. The CCRs were stimulated by phase-synchronized bolus injections of CO2-saturated saline into the common carotid arteries. Only those neurons whose discharge time course was altered by both inflation and CCR activation were studied. The dorsal respiratory group (DRG) I inflation-insensitive neurons were also included. Cycle-triggered histograms of unit activity were obtained for the neuronal responses to inflation, CO2 bolus, and their combination, as well as for the spontaneous control condition. Linearity of the interaction was tested by comparing the sum of the net individual responses to the net response of the combined afferent inputs. The results suggest that a linear (additive) interaction between CCR and PSR inputs exists for the DRG I inflation-sensitive neurons, the ventral respiratory group (VRG) I decrementing, and caudal VRG E augmenting neurons, while a nonadditive interaction exists for caudal VRG E decrementing bulbospinal neurons. The implications of these findings are discussed.
Peripheral angiotensin causes salt appetite in rats
Authors: Thunhorst R. L. , Fitts D. A.
Published: December 2017

The prevailing theory of sodium depletion-induced salt appetite states that angiotensin (ANG) of cerebral origin, not of renal origin, causes the behavior. This assertion depends partly on an experiment that suppressed salt appetite using an intravenous infusion of a dose of angiotensin-converting enzyme (ACE) inhibitor (captopril, 2.5 mg/h) that supposedly blocked both central and peripheral enzyme (17). The present experiments used the same dose of captopril to suppress salt appetite both in 24-h and in 3-h models of sodium depletion-induced behavior. The captopril-infused rats 1) increased water intake normally after central injections of ANG I given immediately after each salt appetite test, 2) had no arterial pressor response after intravenously injected ANG I, and 3) had normal arterial pressor responses after either intravenously injected ANG II or centrally injected ANG I. Thus, although the peripheral ACE was completely blocked in captopril-infused rats, the central ACE was not, because the central thirst and arterial pressor responses to ANG I were indistinguishable from controls. This demonstrates that ANG of renal origin is necessary for the expression of sodium depletion-induced salt appetite.
Modulation of food intake by peripherally administered amylin
Authors: Morley J. E. , Flood J. F. , Horowitz M. , Morley P. M. , Walter M. J.
Published: December 2017

Amylin has been demonstrated to produce anorexia in rodents. Its mechanism of action is unknown. We have studied the effect of amylin on food intake in mice in a variety of paradigms to determine whether it inhibits food intake by a peripheral mechanism of action. In addition, we determined its effect in genetically obese mice models and whether its effects differed in aged mice. Cholecystokinin is the prototypic satiety agent. The effects of amylin on reducing food intake were not attenuated by the cholecystokinin antagonist L-364718, suggesting that it does not produce its effect through the release of cholecystokinin. A number of gastrointestinal peptides produce anorexia by stimulating ascending vagal fibers. For this reason, we studied the effect of truncal vagotomy on the suppression of feeding induced by amylin. Vagotomy did not prevent amylin from inhibiting food intake. Amylin was equally effective at reducing food intake in genetically obese (ob/ob) and lean (ob/c) mice and in diabetic (db/db) and lean (db/c) mice. Amylin effectively suppressed food intake in mice over the age of 4-22 mo. These studies further support the role of the pancreatic hormone amylin as a peripherally acting satiety agent.