bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuromodulation of ion transport in porcine distal colon: NPY reduces secretory actions of leukotrienes
Authors: Traynor T. R. , Brown D. R. , O'Grady S. M.
Published: December 2017

Electrical transmural stimulation (ETS) was used to examine the neuroregulation of electrolyte transport in the porcine distal colon. ETS of the colonic mucosa-submucosa mounted in Ussing chambers produced rapid and transient increases in short-circuit current (Isc) that were inhibited 36% by serosal bumetanide, suggesting that a portion of the response may be attributed to Cl secretion. ETS actions were dependent upon stimulus intensity and frequency and were inhibited by tetrodotoxin and omega-conotoxin. Prazosin and pyrilamine had no effect on the mucosal responses to ETS, whereas atropine reduced the responses by 32%. Neuropeptide Y (NPY) also reduced the mucosal responses to ETS up to 60% (half-maximal effective concentration = 17 nM). In addition, the effects of leukotriene C4, previously shown to stimulate Cl secretion via a neuronal pathway, were also inhibited by NPY. These results indicate that cholinergic submucosal neurons play a role in the regulation of epithelial ion transport and that NPY acts as an inhibitory neuromodulator, particularly on leukotriene-sensitive neurons in the porcine distal colon.
Intraluminal lipids modulate avian gastrointestinal motility
Authors: Martinez V. , Jimenez M. , Gonalons E. , Vergara P.
Published: December 2017

Infusion of lipids into the ileum delays gastric emptying and intestinal transit time in some species. The aim of this study was to characterize the actions of intraluminal lipid infusion on gastrointestinal electrical activity in chickens. Animals were prepared for electromyography with chronic electrodes in stomach, duodenum, and small intestine. Two catheters were chronically placed in the esophagus and ileum to infuse equimolar doses of either oleic acid (OA) or triolein (TO). Both OA and TO, esophageally infused, inhibited the frequency of the gastroduodenal cycle and increased the frequency of antiperistaltic spike bursts in the duodenum. Ileal infusion of OA, but not of TO, produced the same effects. Both esophageal and ileal OA infusion increased the duration of the migrating myoelectric complex (MMC) and decreased the speed of propagation of phase III. In conclusion, intraluminal infusion of lipids modulates gastrointestinal motility by decreasing the frequency of the gastric cycle, increasing duodenogastric refluxes, and elongating the MMC. These actions could delay gastric emptying and increase transit time, which suggests the presence of an "ileal brake" mechanism similar to that described in mammals.
Intestinal absorption of water-soluble vitamins in channel catfish (Ictalurus punctatus)
Authors: Casirola D. M. , Vinnakota R. R. , Ferraris R. P.
Published: December 2017

The absorption of selected water-soluble vitamins was studied in isolated intestinal sleeves of channel catfish (Ictalurus punctatus). The uptakes of riboflavin and biotin were each inhibited by their nonlabeled form, indicating the presence of a saturable mechanism [riboflavin: Michaelis constant (Km), 4.84 +/- 1.23 microM; maximal velocity (Vmax), 0.59 +/- 0.07 pmol.mg-1.min-1 biotin: Km, 22.3 +/- 6.95 microM; Vmax, 0.67 +/- 0.10 pmol.mg-1.min-1]. In contrast, the uptakes of nicotinamide, folic acid, and its metabolic derivative 5-methyltetrahydrofolate were not significantly inhibited by their respective nonlabeled forms. Their uptakes were a linear function of concentration [dissociation constant, 0.173 +/- 0.006, 0.050 +/- 0.002, and 0.031 +/- 0.004 pmol.mg-1.min-1.microM-1, respectively]. Folic acid was absorbed more rapidly than 5-methyltetrahydrofolate, and neither vitamin inhibited the absorption of the other. Intestinal uptake of riboflavin and biotin is carrier mediated, whereas uptake of nicotinamide, folic acid, and 5-methyltetrahydrofolate occurs by simple diffusion. These mechanisms are similar to those found in mammals for the same vitamins, except for the hydrophobic folates, which are actively transported in mammals but where diffusion may suffice to fulfill metabolic requirements of catfish.
Depressed expression of the inducible form of HSP 70 (HSP 72) in brain and heart after in vivo heat shock
Authors: Beck S. C. , Paidas C. N. , Tan H. , Yang J. , De Maio A.
Published: December 2017

The heat shock gene expression plays a role in the protection of cells from injury. In the present study, we have analyzed the expression of heat shock protein (HSP) 72 (the major inducible form of the HSP 70 family) in different rat organs after a total body hyperthermia. The content of HSP 72 was greatest in liver and colon. In contrast, accumulation of HSP 72 was low in heart and brain (3-5% and < 1% of the amount in liver, respectively). This low expression of HSP 72 in heart and brain could not be explained by a difference in the actual temperature within these organs. Analysis of cells in culture that resemble hepatocytes, myoblast, and neurons showed a pattern of HSP 72 expression similar to that observed in liver, heart, and brain in vivo after heat shock. These results suggest that this disparate expression of HSP 72 is due to intrinsic characteristics of the cell types rather than to physiological or environmental conditions. The differential expression of HSP 72 among different cell lines could be correlated with the different levels of protein synthesis protection.
Arginine synthesis in enterocytes of neonatal pigs
Authors: Wu G. , Knabe D. A.
Published: December 2017

Arginine is deficient in porcine colostrum and milk, and yet the piglet has a particularly high requirement for this essential amino acid for rapid postnatal growth. To explain this paradox, arginine synthesis was quantified in enterocytes from newborn (0-day-old) and 2- to 7-day-old suckling pigs. Arginine was found to be synthesized from glutamine in 0- to 7-day-old pig enterocytes, but the rates of arginine synthesis were three- to fourfold greater in 0- to 2-day-old pigs than in 7-day-old pigs. To elucidate the developmental change of the intestinal arginine synthesis, the metabolism of glutamine to citrulline, the conversion of citrulline to arginine, and the activities of the enzymes involved were measured. The rates of metabolism of glutamine to citrulline were 2.5- to 3.5-fold greater in enterocytes from 0- to 2-day-old pigs than in cells from 7-day-old pigs, as were the rates of conversion of citrulline to arginine. The activities of all enzymes that synthesize arginine from glutamine, except pyrroline-5-carboxylate synthase and argininosuccinate lyase (ASL), increased in enterocytes from 2-day-old pigs compared with 0-day-old pigs. The activities of all these enzymes decreased by approximately 75% in 7-day-old pigs compared with 2-day-old pigs. Arginase activity was negligible in enterocytes from 0- to 7-day-old pigs, thus minimizing intestinal hydrolysis of newly synthesized arginine and maximizing the endogenous provision of arginine. The results of this study demonstrate the presence of arginine-synthesizing enzymes and their developmental changes in postnatal pig enterocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II and cardiovascular regulation in a freshwater teleost, Anguilla rostrata LeSueur
Authors: Oudit G. Y. , Butler D. G.
Published: December 2017

Cardiac output (CO), dorsal aortic blood flow (BFDA) and blood pressure (PDA), and heart rate (HR) were recorded simultaneously in conscious freshwater eels. Physiological doses of [Asn1,Val5]angiotensin II (ANG II; 25-150 ng/kg iv) were used to investigate its effects on the blood flow [CO, BFDA, and estimated branchial shunting (BS)] and systemic vascular resistance (RSys) components of the pressor response and possible mechanism(s) of action. CO was increased mainly by an elevated stroke volume (SV) due to positive inotropy and/or Frank-Starling principle in a dose-related manner. An intact baroreceptor reflex attenuated the blood flow increase by 25% via the inhibitory cardiac vagal innervation. The elevation in estimated BS was a passive response to the increased CO, since the proportion of CO perfusing the pathway remained constant. PDA showed a similar dose-dependent increase in response to ANG II but the peak PDA preceded the peak CO responses at all doses; RSys was only transiently elevated at peak PDA. The increase in blood flow was an important contributor to the vasopressor responses. Alpha-Adrenergic blockade partially inhibited the pressor effect of ANG II (100 ng/kg) primarily by attenuating the increase in blood flow (50-70%). The data provide evidence for an ANG II-mediated cardiovascular control in teleosts directly and indirectly via catecholamine release.
Oxygen consumption, acid-base status, and behavior during and after acute, severe hemorrhage in fetal lambs
Authors: Kwan E. , Rurak D. W. , Taylor S. M.
Published: December 2017

The metabolic and behavioral effects of 40-45% hemorrhage (at approximately 1%/min) were studied in nine fetal lambs in utero (130-135 days of gestation) until 2 days posthemorrhage. Umbilical blood flow (Qum) fell from 192 +/- 14 to 100 +/- 9 ml.min-1.kg-1 at the end of blood loss, and on the day of hemorrhage it was linearly related to blood volume. However, on the posthemorrhage days, Qum was restored even though blood volume was still reduced. Fetal O2 delivery (DO2) fell with the decrease in Qum and later due to anemia (decrease in hematocrit from 33.4 +/- 1.2 to 23.6 +/- 1.2%), from 946 +/- 81 to 494 +/- 47 mumol.min-1.kg-1, but the decrease was lessened because of a rise in umbilical venous PO2 (31.7 +/- 2.6 to 45.9 +/- 2.8 mmHg). Fetal O2 consumption was reduced during and for 2 h after hemorrhage (262 +/- 17 to 190 +/- 16 mumol.min-1.kg-1), and this was associated with modest lactic acidemia (1.25 +/- 0.11 to 2.91 +/- 0.43 mM). There was also a temporary reduction in fetal breathing activity, low voltage electrocortical state, and rapid eye movements, but this was not associated with hypoxemia. It is concluded that reductions in fetal DO2 achieved via fetal blood loss are better tolerated than during hypoxemia and that the associated depression in fetal biophysical activities involves mechanisms other than systemic hypoxia.
Impaired gut lipid absorptive capacity after trauma-hemorrhage and resuscitation
Authors: Kerner J. , Wang P. , Chaudry I. H.
Published: December 2017

Although the barrier function of the intestinal mucosa is impaired after hemorrhage, it remains unclear whether this is associated with a deficit in mucosal function. The aim of this study, therefore, was to determine whether trauma-hemorrhage affects the in vivo lipid absorptive capacity of the gut and, if so, to characterize the uptake process of free fatty acids in isolated enterocytes. To study this, rats were anesthetized, a laparotomy was performed (i.e., trauma was induced), and various blood vessels were cannulated. For in vivo lipid absorption, the main intestinal lymph vessel was cannulated and a jejunostomy feeding tube was inserted. The animals were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of shed blood volume was returned in the form of Ringer lactate. They were then resuscitated with four times the volume of maximal bleed out with Ringer lactate. The in vivo and in vitro lipid absorptive capacities were assessed by measuring lymph triglyceride output after a fat load and by determining the linoleic acid uptake rates on isolated enterocytes, respectively. The results show that the in vivo lipid absorption capacity of the gut is severely depressed after trauma-hemorrhage and resuscitation. Similarly, in enterocytes isolated from hemorrhaged rats, fatty acid uptake capacity, as reflected by the decreased maximal uptake rates, was significantly reduced: 1.2 +/- 0.2 and 2.6 +/- 0.6 nmol.min-1 x 10(6) cells-1 for hemorrhaged and sham, respectively. Thus gut lipid absorptive function is depressed after trauma-hemorrhage and resuscitation, which is at least partially due to the depressed uptake mechanism of the enterocyte.
Chronic lung lymph fistula that only drains the left lung
Authors: Kikuchi Y. , Nakazawa H. , Traber D. L.
Published: December 2017

We developed a chronic lung fistula that drains only the left lung, allowing for evaluation of injury in a single lung. To remove lymph drainage from the right lung into the caudal mediastinal lymph node, the right lower pulmonary ligament was severed. Pneumatic occluders were placed on the left pulmonary arteries and veins. To ensure that lymph drained from only the left lung, we increased the right pulmonary arterial pressure (RPAP) from 21.2 +/- 0.5 to 36.5 +/- 0.6 mmHg. The left pulmonary arterial pressure (LPAP) was kept at wedge pressure level for 1 h by inflating pneumatic occluders. Lymph flow from the left lung fistula was stable during this occlusion. Six hours after recovery was increased the LPAP from a baseline level of 19.1 +/- 1.0 to 36.4 +/- 0.9 mmHg and the RPAP from 21.2 +/- 0.5 to 38.0 +/- 0.8 mmHg for 2 h by inflating the pneumatic occluders on the left and right pulmonary veins. Lymph flow increased from 5.3 +/- 1.0 to 28.0 +/- 2.9 ml/h. Reflection coefficient was calculated at 0.80 +/- 0.02.
Effect of acute manipulation of blood volume and osmolality on plasma [AVT] in seawater flounder
Authors: Warne J. M. , Balment R. J.
Published: December 2017

Chronically cannulated seawater (SW)-adapted flounder (Platichthys flesus) were used unanesthetized and unrestrained in an experimental series that acutely manipulated blood volume and plasma osmolality to determine their influence on plasma arginine vasotocin (AVT) concentrations. Immunoreactive AVT was measured using a radioimmunoassay validated for flounder and other teleosts. After hemorrhage-induced hypovolemia or hypervolemia produced by saline infusion, no major changes in plasma AVT concentrations were detected. Raising plasma osmolality by intraperitoneal injection of 1 M NaCl compared with control 150 mM NaCl-injected fish (329.4 +/- 3.4 vs. 320.4 +/- 3.0 mosmol/kgH2O, P < 0.05) produced an increase in plasma AVT concentration (6.7 +/- 1.2 vs. 4.2 +/- 0.2 fmol/ml, P < 0.05). In a separate study, plasma composition in a large number of uncannulated SW-adapted flounder was determined. This demonstrated a positive linear relationship between the natural variation in plasma AVT concentrations and plasma osmolality and Na+ and Cl- concentrations observed between fish. These data indicate that AVT secretion in SW-adapted flounder is closely related and perhaps directly sensitive to changes in plasma tonicity.
Ontogenetic development of gut function, growth, and metabolism in a wild bird, the Red Jungle Fowl
Authors: Jackson S. , Diamond J.
Published: December 2017

We measured the ontogeny of growth rate, food intake, metabolic rates, organ masses, and intestinal nutrient transporter and hydrolase activities in a wild bird for comparison with previous measurements of the same quantities in four domesticated or laboratory animals. Analysis of covariance with body mass as a covariate showed that body mass accounted for most of the age-related variation in all variables, but that age itself still had a significant effect on most variables. Among organs studied, the ceca exhibited the greatest mass increase with age. Energy intake and resting and basal metabolic rates increased with age, but digestive efficiency, cost of growth, and sustained metabolic scope were independent of age. Although intestinal brush-border glucose and proline uptakes and sucrase activity declined with age, the corresponding capacities increased with age because of compensating increases in intestinal mass. Intestinal passive permeability to glucose was undetectably low. Unlike the four domesticated animals studied to date, jungle fowl possess no intestinal reserve capacities (excesses of capacity over dietary nutrient intake). Cecal absorption may contribute significantly to glucose uptake capacity with increasing age.
ANG II receptor blockade and arterial baroreflex regulation of renal nerve activity in cardiac failure
Authors: DiBona G. F. , Jones S. Y. , Brooks V. L.
Published: December 2017

In cardiac failure, efferent renal sympathetic nerve activity (ERSNA) and the activity of the renin-angiotensin system are increased, and arterial baroreflex regulation of ERSNA is attenuated. We examined the effect of intravenous and intracerebroventricular angiotensin II AT receptor blockade with losartan on the arterial baroreflex regulation of ERSNA in conscious control (C) and congestive heart failure (CHF) rats. Intravenous losartan (10 mg/kg, 21.7 mumol/kg) decreased arterial pressure more in CHF than in C rats (-28 +/- 3 vs. -20 +/- 3 mmHg, P < 0.05). After restoration of arterial pressure to the prelosartan value with methoxamine infusion, ERSNA was decreased more in CHF than in C rats (-23 +/- 4 vs. -1 +/- 2%, P < 0.05). Maximal gain of arterial baroreflex control of ERSNA (Gmax) was lower in CHF compared with C rats (-1.94 +/- 0.10 vs. -3.78 +/- 0.21%/mmHg, P < 0.05). Intravenous losartan increased Gmax in CHF (to -3.01 +/- 0.14%/mmHg, P < 0.05) but not in C rats (to -3.56 +/- 0.19%/mmHg). Intracerebroventricular losartan (4.61 micrograms, 10 nmol) did not affect arterial pressure but decreased ERSNA more in CHF than in C rats (-13 +/- 2 vs. -8 +/- 3%, P < 0.05). Like intravenous losartan, intracerebroventricular losartan increased Gmax in CHF (from -2.11 +/- 0.18 to -3.21 +/- 0.30%/mmHg, P < 0.05) but not in C rats (from -3.98 +/- 0.25 to -3.84 +/- 0.22%/mmHg). These results suggest that increased activity of the renin-angiotensin system contributes to the increase in ERSNA and its abnormal arterial baroreflex regulation in cardiac failure.
Cardiovascular and neurohormonal effects of intravenous adrenomedullin in conscious rabbits
Authors: Fukuhara M. , Tsuchihashi T. , Abe I. , Fujishima M.
Published: December 2017

Adrenomedullin is a vasodilative peptide and shows slight homology with calcitonin gene-related peptide. In the present study, we investigated the effects of adrenomedullin on cardiovascular and neurohormonal responses in 13 conscious rabbits. The animals were chronically instrumented with bipolar electrodes on the left renal sympathetic nerve. Intravenous administration of human adrenomedullin (10, 100, 1,000, and 3,000 pmol/kg, n = 6) caused a dose-dependent reduction in mean arterial pressure (0 +/- 2, -1 +/- 2, -19 +/- 2, and -29 +/- 4 mmHg, respectively) concomitant with increases in heart rate, renal sympathetic nerve activity, plasma renin activity, and plasma norepinephrine. The significant reduction in mean arterial pressure induced by 1,000 pmol/kg of adrenomedullin occurred within 1 min after injection and lasted for 15 min (n = 7). In contrast, the significant increases in heart rate and renal sympathetic nerve activity lasted for more than 50 min. When mean arterial pressure was decreased by 15 mmHg by adrenomedullin, the increases in heart rate and renal sympathetic nerve activity were 53 +/- 8 beats/min and 78 +/- 13%, respectively, which were significantly smaller than those induced by intravenous injection of sodium nitroprusside (102 +/- 14 beats/min and 155 +/- 34%, respectively). These results suggest that intravenous adrenomedullin exerts a hypotensive action that is associated with the attenuated reflex-mediated sympathetic activation.
Thermal and behavioral effects of lipopolysaccharide and influenza in interleukin-1 beta-deficient mice
Authors: Kozak W. , Zheng H. , Conn C. A. , Soszynski D. , van der Ploeg L. H. , Kluger M. J.
Published: December 2017

This study characterized body temperature (Tb), locomotor activity (Act), and feeding behavior under normal conditions and following injection with lipopolysaccharide (LPS) or inoculation with live influenza virus of transgenic C57/black mice deficient in interleukin-1 beta (IL-1 beta). Tb and Act in freely moving mice were measured by biotelemetry. Mice deficient in IL-1 beta had normal circadian rhythm of Tb but were less active than their control counterparts. Mice injected with LPS (2.5 mg/kg i.p.) responded with a prompt decrease of Tb, which lasted approximately 10 h, followed by a fever in which Tb reached a peak at approximately 24 h postinjection. There was no difference between groups in the early drop of Tb after the LPS; however, the 24-h peak of Tb was lower in IL-1 beta-deficient mice. The anorexic effects of LPS and influenza infection were similar in both groups of mice. In mice given influenza virus (17.5 plaque-forming units, median lethal dose), Tb and Act gradually decreased. The fall of Tb was smaller in the transgenic mice. The mice deficient in IL-1 beta displayed a higher mortality rate due to influenza infection than the control mice. We conclude that deficiency in IL-1 beta results in lower fever following the LPS injection and in impairment of the defense response to infection with influenza.
Hepatic portal insulin antibody infusion increases, but insulin does not alter, spontaneous meal size in rats
Authors: Surina-Baumgartner D. M. , Langhans W. , Geary N.
Published: December 2017

To investigate the acute effects of pancreatic insulin on spontaneous feeding in rats fed ad libitum, insulin or insulin antibodies were infused into the hepatic portal vein during the first meal of either the light or dark phase. Infusions (3 min, 0.033 ml/min) were remotely controlled, and a computerized system recorded meal patterns. In separate crossover tests, 1, 2, 4, 8, and 16 mU insulin/meal did not affect meal size or subsequent intermeal interval (P > 0.10). In one test, nocturnal meal duration was decreased by 2 mU insulin/meal (19%, P < 0.05). Infusions of polyclonal antibodies to human insulin with in vitro rat insulin binding capacity of 20 or 50 mU increased the size of the first nocturnal meal by 24 and 29% (P < 0.05), respectively. Meal duration was reliably increased only by the smaller antibody dose. Subsequent intermeal interval was unaffected by either antibody dose. The stimulatory effect of insulin antibody infusion on meal size indicates that antagonism of circulating insulin during meals interferes with the control of meal termination. Thus insulin appears to play a role in the physiological control of nocturnal spontaneous feeding in rats. Exogenous insulin may have failed to decrease meal size because of a ceiling effect.
Depressed sensitivity of the hepatoportal NaCl receptors in rats with carbon tetrachloride-induced liver cirrhosis
Authors: Tanaka K. , Matsuda T. , Morita H. , Hosomi H.
Published: December 2017

In normal rats, the activity of the hepatoportal NaCl-sensitive afferent nerves is increased by portal injection of hypertonic NaCl. In the present article, we have found this effect to be markedly reduced in rats with CCl4-induced liver cirrhosis (CT rats). Liver tissue norepinephrine content, a marker of tissue innervation, was also decreased in the treated rats. Over the 12 wk CCl4-treatment period, no significant difference in Na balance was found between control and CT rats when both groups were given normal NaCl (0.45%) food. However, when both were given high NaCl (8%) food, the Na balance of CT rats was positive and greater than that of controls. These results indicate that the sensitivity of the hepatoportal NaCl receptors is decreased even when the degree of liver cirrhosis is slight. This mechanism plays an important role in maintaining Na balance during intake of high NaCl food.
Spectral analysis of arterial pressure lability in rats with sinoaortic deafferentation
Authors: Jacob H. J. , Ramanthan A. , Pan S. G. , Brody M. J. , Myers G. A.
Published: December 2017

Traditionally, the standard deviation (SD) of the mean arterial pressure (AP) has been used as an index for the AP lability produced by interruption of baroreceptor afferents. Although a useful measure of variance about the mean, the SD does not provide any information about the temporal characteristics of this variability. We employed two different spectral analytic techniques to characterize AP waveforms in rats with sinoaortic deafferentation (SAD) and in sham-operated (Sham) rats to determine if the AP waveform in SAD animals was qualitatively and/or quantitatively different from that of Sham animals. The SAD and Sham animals exhibited qualitatively different spectral profiles, suggesting that lability of AP in SAD animals is not simply an exaggeration of normal fluctuations. In addition, a low-frequency (0.3-0.5 Hz) spectral peak was found in Sham but not SAD animals, suggesting that it is associated with the baroreflex. Finally, we observed in both normal rats and rats without intact baroreceptors that the spectral components of AP are not static but rather vary continuously across time.
Increased nitric oxide activity in early renovascular hypertension
Authors: Dubey R. K. , Boegehold M. A. , Gillespie D. G. , Rosselli M.
Published: December 2017

A decreased influence of nitric oxide (NO) in the peripheral vasculature is associated with the pathophysiology of established hypertension, and some studies suggest that increased blood pressure positively correlates with decreased NO production. If so, then the increased arterial pressure in one-kidney, one-clip (1K1C) hypertensive rats should be associated with decreased circulating levels of nitrite/nitrate (NO2/NO3; stable metabolites of NO) and guanosine 3',5'-cyclic monophosphate (cGMP; mediator of NO action). We measured serum NO2/NO3 and cGMP levels in early hypertensive 1K1C (2 wk after clipping) and shamoperated one-kidney (1K) normotensive rats, treated orally with or without the NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 2 wk). Compared with those in 1K rats, NO2/NO3 and cGMP levels were increased in 1K1C hypertensive rats but not in 1K1C rats treated with L-NAME. NO2/NO3 and cGMP levels in L-NAME-treated 1K and 1K1C rats were similar. Compared with that in 1K rats, systolic blood pressure (SBP) was increased in 1K1C rats and in L-NAME-treated 1K and 1K1C rats. The SBP increase in L-NAME-treated 1K1C rats was more rapid than in untreated 1K1C rats. In early hypertension, increases in SBP positively correlated with increases in serum NO2/NO3 and cGMP. After 2 wk of hypertension, circulating NO2/NO3 levels gradually declined and reached prehypertension levels by the fifth week of hypertension. These results provide evidence for increased NO synthesis in early hypertensive 1K1C rats, and this increased NO could be a compensatory mechanism to slow the development of hypertension in these animals.
Formation and actions of 20-hydroxyeicosatetraenoic acid in rat renal arterioles
Authors: Imig J. D. , Zou A. P. , Stec D. E. , Harder D. R. , Falck J. R. , Roman R. J.
Published: December 2017

The present study examined whether preglomerular arterioles of the rat produce 20-hydroxyeicosatetraenoic acid (20-HETE) and whether 20-HETE is vasoactive on these vessels. Raf preglomerular arterioles produced 20-HETE (4.8 +/- 1.0 pmol.min-1.mg-1, n = 7) and, to a lesser extent, 14-, 15-, 11-, and 12-dihydroxyeicosatetraenoic acid, 6-ketoprostaglandin F/alpha and prostaglandin E2 when incubated with [14C]larachidonic acid. The results of immunoblotting and reverse-transcription polymerase chain reaction experiments indicate that these vessels express mRNA and protein for a P-450 4A2 enzyme. With the use of a rat juxtamedullary nephron microvascular preparation perfused in vitro with a cell-free media, addition of 20-HETE (1 nM-1 microM) to the bath reduced the diameter of proximal and distal portions of the efferent arterioles. At a concentration of 1 microM, the diameter of the proximal and distal portions of the afferent arteriole fell by 14 +/- 1 and 16 +/- 3% after 20-HETE. The response to 20-HETE (1 microM) was not altered by blockade of cyclooxygenase, lipoxygenase, and p-450 pathways. Blockade of the large-conductance Ca(2+)-activated K+ channel with tetraethylammonium (1 mM) reduced the diameter of afferent arterioles by 10% and blocked the vasoconstrictor response to 20-HETE (1 microM). These results indicate that 20-HETE is an endogenous constrictor of preglomerular arterioles and suggest a role for the P-450 4A2 enzyme in the regulation of renal vascular tone.
Initial externalization followed by internalization of beta-adrenergic receptors in rat heart during sepsis
Authors: Tang C. , Liu M. S.
Published: December 2017

Changes in the distribution of beta-adrenergic receptors in two subcellular fractions, the sarcolemma and the light vesicle, of rat heart during sepsis were studied, using [3H]dihydroalprenolol ([3H]DHA) binding and photoaffinity labeling with [125I]iodocyanopindolol ([125I]ICYP). Sepsis was induced by cecal ligation and puncture (CLP). Septic rat hearts exhibit an initial hypercardiodynamic (9 h after CLP; early sepsis) and a subsequent hypocardiodynamic (18 h after CLP; late sepsis) state. [3H]DHA-binding studies show that, during early sepsis, the maximum binding capacity (Bmax) was increased by 35% in sarcolemma but was decreased by 25% in light vesicles, whereas during late sepsis, the Bmax was decreased by 39% in sarcolemma but was increased by 30% in light vesicles. Photoaffinity labeling studies show that the incorporation of [125I]ICYP into 64,000-Da peptide during early sepsis was increased by 32% in sarcolemma but was decreased by 27% in light vesicles, whereas during late sepsis, the incorporation was decreased by 30% in sarcolemma but was increased by 35% in light vesicles. These data indicate that beta-adrenergic receptors in the rat heart were externalized from light vesicles to sarcolemma during the hyperdynamic phase but were internalized from surface membranes to intracellular sites during the hypodynamic phase of sepsis. Because beta-adrenergic receptors mediate adrenergic control of cardiac muscle contraction, a biphasic intracellular redistribution of beta-adrenergic receptors in the heart may contribute to the development of the initial hypercardiodynamic and subsequent hypocardiodynamic states during sepsis.
Medullary vasomotor activity and hypoxic sympathoexcitation in pentobarbital-anesthetized rats
Authors: Sun M. K. , Reis D. J.
Published: December 2017

In pentobarbital sodium-anesthetized, paralyzed, and ventilated rats, systemic hypoxia, produced by intratracheal N2 administration for 20 s, rapidly increased activities of reticulospinal vasomotor neurons in the rostroventolateral reticular nucleus (RVL) of the medulla oblongata (by 23.9 +/- 4.7 spikes/s) and sympathetic nerves (by 30.9 +/- 4.7 microV) and arterial pressure (by 35.6 +/- 6.4 mmHg). The sympathoexcitatory and pressor responses were abolished by bilateral microinjections of muscimol, a gamma-aminobutyric acid (GABA)A-receptor agonist, (250 pmol per 50 nl/site) into the RVL. Chemical inhibition of RVL also reduced arterial pressure to 48.1 +/- 3.7 mmHg and eliminated sympathetic nerve activity. Intravenous infusion of L-phenylephrine and intrathecal administration of kainic acid restored arterial pressure to control level but not the rapid sympathoexcitatory responses to acute hypoxia. We conclude that, in pentobarbital-anesthetized rats, the sympathetic vasomotor tone and pressor responses to acute hypoxia depend on activity and excitation of RVL-spinal vasomotor neurons. The neural mechanisms responsible for the sympathetic tone and rapid pressor responses to hypoxia in these animals qualitatively differ neither from those anesthetized with urethan nor from the decerebrate unanesthetized animals.
Effects of vasopressin V1-receptor blockade during acute and sustained hypovolemic hypotension
Authors: Wall B. M. , Huch K. M. , Runyan K. R. , Williams H. H. , Gavras H. , Cooke C. R.
Published: December 2017

The response of vasopressin and its role in the maintenance of arterial pressure during and after development of hypotensive central hypovolemia were studied in tilt table studies in quadriplegic subjects. The studies were performed during acute head-up tilting to a maximally tolerated degree of tilt (8 subjects) and during sustained head-up tilt following a 20% reduction in mean arterial pressure (MAP) (11 subjects). Studies in all subjects were performed on two separate days, once with and once without administration of a selective vasopressin V1-receptor antagonist. During acute head-up tilting, plasma vasopressin concentrations (PAVP) did not increase significantly until MAP decreased to approximately 60 mmHg at maximal tilt. There was no difference in the degree of hypotension produced in the presence compared with the absence of V1-receptor blockade. There was also no difference in plasma renin activity (PRA) or in plasma cortisol or aldosterone concentrations at maximal tilt. In contrast, during sustained head-up tilt following a 20% reduction in arterial pressures, systolic and mean arterial pressures were significantly lower and PRA was significantly higher in the presence than in the absence of V1-receptor blockade. PAVP increased and was significantly higher after 30 min of sustained tilt than pretilt PAVP in supine posture. These studies do not provide evidence of a role for vasopressin in the maintenance of arterial pressure during the acute development of hypotensive hypovolemia in human subjects, but they do provide evidence of a modest role for vasopressin in the maintenance of arterial pressure when the effect of hypovolemia is more moderate and sustained.
Hormonal regulation of hepatic gluconeogenesis: influence of age and training
Authors: Podolin D. A. , Gleeson T. T. , Mazzeo R. S.
Published: December 2017

The contributions of three major gluconeogenic regulators, glucagon (10(-7) M), alpha-adrenergic agonist phenylephrine (10(-5) M), and beta-agonist isoproterenol (10(-5) M) to hepatic glucose synthesis in liver slices from Fischer 344 rats were examined in relation to age and endurance training. Young (4 mo), middle-aged (12 mo), and old (22 mo) male Fischer 344 rats (n = 66) were divided into trained or sedentary groups. Trained animals were run 10 wk on a treadmill at 75% of maximal capacity, 1 h/day, 5 days/wk. Animals were killed at rest, and sections of liver were removed and sliced in a tissue microtome. Slices were incubated in L-[U-14C]lactic acid, Ringer solution, and one of the aforementioned gluconeogenic regulators. Rates of lactate incorporation into glucose and glycogen were significantly greater in young compared with old animals for all three regulators in both trained and untrained animals. Training elicited a 35, 52, and 63% improvement in lactate incorporation into glucose compared with untrained when the livers of young (16.9 +/- 1.2 vs. 10.9 +/- 1.1 mumol.g protein-1.min-1), middle-aged (12.8 +/- 1.3 vs. 6.1 +/- 1.2 mumol.g protein-1.min-1), and old (11.2 +/- 1.1 vs. 4.1 +/- 0.6 mumol.g protein-1.min-1) animals, respectively, were incubated in glucagon. Rates with phenylephrine followed a similar pattern to that with glucagon across age and training, but absolute rates were significantly lower. No training effect in gluconeogenic rate was found when liver was incubated in the presence of isoproterenol. It is concluded that the gluconeogenic capacity of liver declines with age regardless of the gluconeogenic regulator and that training was able to partially offset age-related declines in glucagon-stimulated and alpha-receptor-mediated gluconeogenesis.
Dehydration natriuresis in male rats is mediated by oxytocin
Authors: Huang W. , Lee S. L. , Arnason S. S. , Sjoquist M.
Published: December 2017

In a previous study in rats we demonstrated the existence of osmoregulatory natriuretic mechanisms distinct from the natriuretic mechanisms that are dependent on volume stimulation. At the same time, we found that oxytocin (OT) receptors were important mediators of natriuresis induced by hypernatremia but not of that induced by isotonic volume expansion. In the present study, the role of OT in dehydration natriuresis was examined in conscious rats. Dehydration for 24 h caused hypernatremia (from 142.1 +/- 0.4 to 147.7 +/- 0.7 mmol/l) and natriuresis accompanied by an approximately 30% spontaneous reduction of food intake. In conjunction with renal retention of water caused by an increase in circulating vasopressin, the natriuresis and probably the reduction of food intake can help to counteract the rise in body fluid osmolality. This natriuresis could not be fully explained by the reduction in plasma aldosterone. Plasma OT concentration had increased from 15.5 +/- 1.2 to 23.8 +/- 2.0 pg/ml at the end of 24 h of dehydration. Intravenous infusion of a selective OT-receptor antagonist [Mpa1,D-Tyr(Et)2, Thr4, Orn8]-OT using osmotic minipumps prevented dehydration natriuresis. It is concluded that in a dehydration-induced hypernatremic state OT is released, inducing natriuresis and facilitating sodium homeostasis. This mechanism is activated by Na osmoreceptors, but is not primarily dependent on the volume status.
Endotoxin shock: thermoregulatory mechanisms
Authors: Romanovsky A. A. , Shido O. , Sakurada S. , Sugimoto N. , Nagasaka T.
Published: December 2017

To clarify mechanisms of hypothermia in lipopolysaccharide (LPS) shock, four experiments were conducted in 72 chronically instrumented Wistar rats. They were intended to accomplish the following: experiment 1, determine the dose of intravenous Escherichia coli LPS that induces a body temperature (Tb) fall at a minimal mortality [the dose chosen (0.5 mg/kg) was then used in experiments 2-4]; experiment 2, identify the time course of the arterial blood pressure (BP) fall (shock) during the response to LPS; experiment 3, measure threshold Tb values for skin vasodilation and activation of metabolic heat production (M) during the LPS shock; and experiment 4, ascertain behavioral thermoregulation in LPS shock. For experiments 1-3, rats were kept in restrainers; ambient temperature (Ta) was 26 degrees C. In experiment 4, rats freely moved in a thermogradient (18-33 degrees C). Variables monitored were colonic (Tc) and tail skin (Tsk) temperatures (experiment 1); BP (experiment 2); hypothalamic temperature (Thy), M (from oxygen consumption), and Tsk (experiment 3); and preferred Ta (Tpr) and abdominal temperature (experiment 4). In experiment 1, LPS induced no Tc changes at 0 mg/kg, a biphasic fever (no mortality) at 0.05 mg/kg, a biphasic hypothermia (42% mortality) at 0.5 mg/kg, and a rapid fall of Tc (100% mortality) at 5 mg/kg. LPS-induced (0.5 mg/kg) hypotension (experiment 2) occurred simultaneously with the first hypothermic phase; both Tc and BP reached their nadirs (-0.8 +/- 0.1 degrees C and -34 +/- 12 mmHg) at approximately 1.5 h post-LPS. The major autonomic mechanism of the shock hypothermia was a shift in the threshold Thy for M from 37.9 +/- 0.3 to 36.0 +/- 0.3 degrees C (experiment 3; P < 0.05). In experiment 4, rats selected Tpr below 25 degrees C (vs. 28-30 degrees C in control; P < 0.05) throughout the duration of the shock; their Tb dropped to 36.2 +/- 0.3 degrees C (P < 0.05). In sum, the LPS shock-associated hypothermia involves a decrease in the threshold Tb for M, the resultant widening of the interthreshold zone, and cold-seeking behavior.
Time course of saline-induced recovery of the gustatory system in sodium-restricted rats
Authors: Stewart R. E. , Hill D. L.
Published: December 2017

Placing pregnant rats on a Na(+)-restricted diet (0.03% NaCl) results in greatly reduced chorda tympani nerve responses to Na+ stimuli in the offspring. Normal responses can be permanently restored by providing offspring one-time access to saline. We tested whether saline-induced recovery occurs in taste receptor cells present at the time of saline intake. Chorda tympani responses were recorded 2 h, 6 h, 24 h, 10 days, and 20 days after saline ingestion. Chorda tympani Na+ responses from Na(+)-restricted rats at 2 h, 6 h, 24 h, and 10 days after saline intake were comparable to responses from control Na(+)-restricted rats. Twenty days after saline consumption, responses to Na+ were significantly elevated compared with control Na(+)-restricted rats. The results indicate that extant taste receptor cells are not substantially influenced by the saline ingestion. Instead, the delayed recovery suggests that taste receptor stem cells exclusively are influenced by saline intake.
Continuous recordings of brain regional circulation during sleep/wake state transitions in rats
Authors: Gerashchenko D. , Matsumura H.
Published: December 2017

Continuous measurement of regional blood flow (RBF) in the brain of a freely behaving rat was attained by a combination of laser-Doppler (LD) flowmetry and our originally devised apparatus, which had been developed for the automatic releasing of the twisting of lines connected between experimental apparatus and the freely behaving animal. RBF changes were studied in a ventral region of the rostral basal forebrain along with sleep-wake states. When compared with the RBF level during slow-wave sleep (SWS), levels of RBF during paradoxical sleep (PS) and wakefulness were higher by 24 (P = 0.0001) and 9% (P < 0.05), respectively. The LD signals suggested that the RBF elevation during PS was produced by dilation of both the large brain arteries and small vessels, whereas the elevation during wakefulness was caused by dilation of small vessels that was counteracted by contraction of large arteries. It was noticed that the original circulation tended to begin changing before the onset of SWS. A circadian rhythm was also demonstrated for the RBF, which largely decreased around the onset of the light period and returned to the high level before the beginning of the dark period. Thus continuous and real-time recordings of regional circulation were performed with satisfactorily precision in freely behaving rats.
In vitro recordings from area postrema neurons demonstrate responsiveness to adrenomedullin
Authors: Allen M. A. , Ferguson A. V.
Published: December 2017

Adrenomedullin (ADM) is a recently discovered 52-amino acid peptide that exerts potent vasodilatory effects in the periphery and influences the control of body fluid balance when injected centrally. In this study extracellular single-unit recordings were obtained from 94 AP neurons in rat brain slices. Bath application of ADM (10(-7) M) excited 47% (32 of 68) of cells tested, and these effects were found to be dose dependent from 10(-7) to 10(-9) M. Excitation was maintained during synaptic blockade in a low-Ca2+ artificial cerebrospinal fluid solution, demonstrating direct actions of ADM on these neurons. The remaining cells were either unaffected (n = 25) or inhibited (n = 11) by ADM. ADM (10(-7) M) also influenced the spontaneous activity of 9 (7 inhibited, 2 excited) of 16 neurons located in the nucleus tractus solitarii (NTS). However, these effects could be eliminated during synaptic blockade, suggesting indirect actions of the peptide on NTS neurons. These data demonstrate that a specific population of CNS neurons within the AP are directly influenced by ADM and suggest that ADM may exert its effects on the central control of fluid balance through direct actions at this circumventricular organ.
Intestinal fat differentially suppresses sham feeding of different gustatory stimuli
Authors: Foster L. A. , Nakamura K. , Greenberg D. , Norgren R.
Published: December 2017

To determine the intestinal contribution to short-term satiety for solutions of varying palatability, 10 ml of either 0.15 M NaCl or lipid (Intralipid: 0.125, 0.25, 0.5, and 1.0 kcal/ml) was infused at a rate of 0.5 ml/min into the duodenum of rats that were sham feeding either a liquid diet (0.5 kcal/ml), 0.3 M sucrose (0.4 kcal/ml), or a 0.1 M solution of glucose polymers (Polycose 0.4 kcal/ml). Differences in palatability were estimated by the total consumption of each solution over 90 min in a one-bottle test. The intake of solutions maximally ingested during the saline infusions (Polycose > Sucrose > liquid diet) was the most sensitive to the lipid infusions. All four lipid concentrations suppressed intake of Polycose, the solution consumed the most; the three highest concentrations suppressed intake of sucrose (intermediate consumption), and only the two highest concentrations suppressed intake of the complete diet, the solution consumed the least. Nevertheless, the duration of suppression was shorter for the solutions the rats drank the most. For the solution the rats drank the least (liquid diet), the two high concentrations of lipid that suppressed intake did so for the entire experimental period, whereas for Polycose, al lipid infusions suppressed intake, but it recovered to control levels for all but the highest concentration. Other studies have reported that increasing diet palatability shortens the duration of satiety. The current results suggest that this effect may reflect the duration of intake suppression elicited by nutrients in the intestine.
Enhanced natriuretic response to intrarenal infusion of atrial natriuretic factor during ovine pregnancy
Authors: Fan L. , Mukaddam-Daher S. , Gutkowska J. , Nuwayhid B. S. , Quillen E. W.
Published: December 2017

Volume-loading and intravenous infusion studies have suggested that the natriuretic response of atrial natriuretic factor (ANF) is blunted or unaltered during pregnancy, but these findings may be influenced by changes in peripheral metabolism or clearance. To better define the direct renal actions of ANF, three doses (0.3, 1.5, and 3.0 pmol.kg-1.min-1) of ANF were infused directly into the renal artery of nonpregnant (n = 7) and 115- to 135-day pregnant (n = 6) unilaterally nephrectomized conscious sheep. Each dose was administered on a separate day according to a protocol that consisted of two 20-min control periods, two 20-min ANF infusions, and three 30-min recovery periods. The levels of basal mean arterial pressure averaged 86 +/- 25 mmHg and were similar and constant throughout all protocols in nonpregnant and pregnant ewes. Glomerular filtration rate (GFR) and renal blood flow (RBF) were increased during pregnancy, but GFR, RBF, and fractional proximal tubular reabsorption were not significantly altered by infusion of ANF. Nonpregnant sheep exhibited a selective renal response that was limited to an increase in urinary sodium excretion (UNaV). Pregnant sheep exhibited a selective renal response that included increases in UNaV and urine flow rate produced by suppression of distal sodium and, presumably, fluid reabsorption. The natriuretic and diuretic response of pregnant sheep was much greater than that of nonpregnant sheep despite a smaller proportional increment in intrarenal ANF concentration. These data suggest that the ovine renal response to ANF is limited to actions on the distal tubule that are enhanced during pregnancy.
Mechanisms of zinc uptake in gills of freshwater rainbow trout: interplay with calcium transport
Authors: Hogstrand C. , Verbost P. M. , Bonga S. E. , Wood C. M.
Published: December 2017

The uptake mechanism of Zn2+ through the gill epithelium of freshwater rainbow trout was investigated both in intact animals and in isolated basolateral membranes. Involvement of the apical Ca2+ uptake sites in Zn2+ uptake was examined in vivo by pharmacological manipulation of the apical Ca2+ permeability. The apical entries of Ca2+ and Zn2+, but not Na2+ and Cl-, were inhibited by addition of La to the water. Addition of 1.0 microM La reduced the influxes of Ca2+ and Zn2+ to 22 +/- 3 and 53 +/- 7% (mean +/- SE) of the control value, respectively. Injection of CaCl2 also reduced the branchial influxes of Ca2+ and Zn2+. This treatment decreased the influx of Ca2- to 45 +/- 4% of the control level and the Zn2+ influx to 68 +/- 5%. These results strongly imply that Zn2+ passes across the apical membrane of the chloride cells of the gills via the same pathway as Ca2+. The presence of an active basolateral transporter for Zn2+ was investigated in vitro on isolated basolateral membranes. There was no ATP-dependent or Na2+(-)gradient driven transport of Zn2+ at physiological Zn2+ activities. The same system was used to study potential effects of Zn2+ on the basolateral Ca2+(-)adenosinetri-phosphatase. Zn2+ was found to be a potent blocker of this transporter, causing a mixed inhibitory effect on the ATP driven Ca2+ transport at a free Zn2+ activity of 100 pM.