bluuebunny/crossref_metadata_2025 huggingface dataset:
24-hour blood pressure recordings in Dahl rats on high- and low-salt diets
Authors: Brown D. R. , Morgan D. A. , Peuler J. D. , Thoren P.
Published: December 2017

The goal of this study was to determine if the baroreflex abnormality previously shown in Dahl-sensitive (DS) rats would increase blood pressure and heart rate (HR) variability. Mean arterial pressure (MAP) and HR were sampled every 2 s for 24 h from Dahl-resistant (DR) and DS rats on low- and high-salt diets (n = 12-13 in each group). MAP +/- SD was significantly elevated in the DS rats on high-salt diets (DSH); the SD of MAP in the DSH rats was also significantly higher compared with similar measurements in rats on high-salt diets (DRH) and DS rats on low-salt diets (DSL) when SD was divided by MAP. MAP was higher at night than during the day in the DSH rats. In contrast, HR and HR variability were not significantly different between the groups. The baroreflex control of HR, determined by means of graded injections of phenylephrine, was least in the DSH rats and increased, respectively, with DSL rats, DRH rats, and DR rats on low-salt diets. There was no significant correlation between the baroreflex control of HR and MAP or the SD of MAP in the DSH rats, suggesting that there is not a simple relationship between baroreflex gain and the overall behavior of MAP in DSH rats.
Anorexic effects of interleukin 1 in the rat
Authors: Mrosovsky N. , Molony L. A. , Conn C. A. , Kluger M. J.
Published: December 2017

Interleukin 1 (IL-1) administration produces anorexia. Among unanswered questions about this effect are 1) whether it plays a role in the cachexia associated with chronic infection and cancer, and 2) whether IL-1 acts directly on food intake or indirectly by first lowering the set point for body weight. To investigate these questions, rats were infused with recombinant IL-1 continuously for 14 days through osmotic minipumps. Tolerance to the anorexic effects of the infusion developed within a few days. Control experiments showed that neither loss of IL-1 potency nor failure in the delivery system were responsible for recovery of food intake. Prior weight reduction completely overrode the anorexic effects of IL-1; previously food-restricted rats were hyperphagic initially despite receiving IL-1. This result is consistent with the view that IL-1 lowers the set point for body weight, but the development of tolerance prevented the full evaluation of this interpretation.
Missing data in two-way analysis of variance
Authors: Slinker B. K. , Glantz S. A.
Published: December 2017

We previously described a regression approach to analysis of variance computations that permitted analysis of unbalanced designs and experiments with missing data in two-way (or higher) analyses of variance Am. J. Physiol. 255 (Regulatory Integrative Comp. Physiol. 24): R353-R367, 1988. That approach can only be used correctly under a set of narrow, and relatively uninteresting, circumstances. In fact, in the example we worked, we extended that approach beyond its intended scope and incorrectly computed F statistics for testing hypotheses about the main effects of strain of rat and nephron site in a study of renal Na(+)-K(+)-adenosinetriphosphatase. This paper presents the correct approach, which can be generalized to most situations likely to be encountered when two-way, or higher, analyses of variance are used.
Evidence of a slow-to-fast fiber type transition in skeletal muscle from spontaneously hypertensive rats
Authors: Ben Bachir-Lamrini L. , Sempore B. , Mayet M. H. , Favier R. J.
Published: December 2017

The histochemical, biochemical, and electrophysiological properties of selected muscles were evaluated in spontaneously hypertensive rats (SHR) and compared with their normotensive Wistar-Kyoto (WKY) counterparts. As early as 4 wk of age, slow muscles (soleus) of SHR displayed a significant alteration in fiber type distribution with a decrease of slow-twitch fibers (from 64 to 53%) and a simultaneous increase of type IIA-fibers (from 19 to 39%). In addition, soleus from young SHR had a significant enhancement of both oxidative (citrate synthase, 3-hydroxyacyl-CoA dehydrogenase) and glycolytic [lactate dehydrogenase (LDH)] capacities, which could be partly related to a capillary rarefaction. During development (from the 4th to the 12-14th wk), in the soleus muscle the histochemical differences between SHR and WKY were amplified, whereas most of the enzymatic differences between strains were abolished, except for a significantly higher LDH activity. These histochemical changes had only marginal repercussions on soleus electrophysiological properties. SHR animals had a significantly higher basal metabolic rate, which could not be accounted for by elevation of thyroid hormones. The origin of the slow-to-fast fiber type transition in slow muscle remains unclear but could be related to the increased level of plasma catecholamines in SHR. Indeed, chronic treatment of rats with a beta 2-receptor agonist has been reported to cause slow-to-fast muscle fiber transition [R. J. Zeman, R. Ludemann, T. G. Easton, and J. D. Etlinger. Am. J. Physiol. 254 (Endocrinol. Metab. 17): E726-E732, 1988].
Diluting segment in kidney of dogfish shark. I. Localization and characterization of chloride absorption
Authors: Friedman P. A. , Hebert S. C.
Published: December 2017

Single tubules, dissected from the peritubular sheath of the dorsal bundle zone of kidney of the dogfish shark, Squalus acanthias, were perfused in vitro at 17-18 degrees C. This segment is the largest of the five in the peritubular sheath and had average inner and outer diameters of 46.9 +/- 1.2 and 74.4 +/- 2.1 microns, respectively (n = 32). These values suggest that this is the intermediate IV segment. When perfused with symmetrical buffered elasmobranch saline, intermediate IV segments exhibited high rates of Cl- absorption (JCl, pmol.s-1.cm-2): 1,696 at an average perfusion rate (Vo) of 8.2 nl/min. Cl- absorption was highly flow dependent [1/JCl = 57.95(1/Vo) + 1.75; r = 0.71, P less than 0.01]. Maximal rates of Cl-absorption, calculated from reciprocal transformation of the flow dependence of JCl, yielded a value of 5,714 pmol.s-1.cm-2. In the presence of a 200-mosmol/kg transepithelial osmotic gradient, fluid absorption was negligible. The spontaneous transepithelial voltage (Vte, mucosal with respect to serosal compartment) averaged 8.0 +/- 1.0 mV (n = 26). Such active transport of Cl- in the absence of fluid movement and in the presence of a lumen-positive transepithelial voltage is characteristic of amphibian and mammalian diluting segments. Na(+)-to-Cl- permeability ratios (PNa/PCl) averaged 2.5 +/- 0.5, indicating that, as in mammalian thick ascending limbs, this segment is Na+ (cation) permselective. Vte was dependent on the presence of Na+ and Cl- in the external solutions and was reversibly abolished by isosmotic replacement with N-methyl-D-glucamine or with isethionate, respectively. Ouabain inhibited Vte but was not reversible within the time course of these experiments. Furosemide (10(-4) M), but not equimolar concentrations of amiloride or hydrochlorothiazide, added to the luminal perfusate inhibited both Vte and JCl. These results suggest that apical membrane Na+ entry in intermediate IV segments is mediated by Na(+)-K(+)-Cl- cotransport and is consistent with the existence of a functional role of urinary dilution in the reabsorption of urea in the elasmobranch kidney.
In vivo endotoxin and IL-1 potentiate insulin secretion in pancreatic islets
Authors: Yelich M. R.
Published: December 2017

This study evaluated the in vivo effects of endotoxin and interleukin 1 (IL-1) on in vitro insulin secretion from perfused rat pancreases and isolated pancreatic islets. Glucose-induced insulin secretion was potentiated in pancreases obtained from rats 3 h after endotoxin or 30 min after IL-1. Studies using isolated pancreatic islets indicated that islet sensitivity to glucose was increased by either endotoxin or IL-1 to a similar extent, but there was no effect of endotoxin or IL-1 on the maximal insulin secretory response of islets to glucose. Insulin secretion was not potentiated in perfused pancreases obtained from rats only 30 min after treatment with endotoxin. These results suggest that in vivo treatment with either endotoxin or IL-1 potentiates insulin secretion by increasing islet sensitivity to glucose. In addition, because endotoxin is known to potently stimulate the production and secretion of IL-1 in vivo, the results lend support to the hypothesis that the effects of endotoxin on insulin secretion may be mediated partially by IL-1.
Resource sharing in rat gestation: role of maternal cardiovascular hemodynamics
Authors: Blizard D. A. , Folk T. G.
Published: December 2017

There is a substantial decrease in blood pressure (BP) in late pregnancy in the laboratory rat. It is so pronounced that manipulations that produce sustained elevations in BP in nonpregnant animals have little or no effect during pregnancy. It is commonly believed that this decrease in BP is a consequence of a large decrease in total peripheral resistance resulting from the passive combination of the placental vasculature with a preexisting maternal vasodilation. An alternative view is presented here. We suggest that, in small mammals like the laboratory rat, pregnancy severely challenges the ability of the maternal cardiovascular system to meet its metabolic demands, so that during the last stages of maturation of the low-resistance placental circulation delivery of vital metabolic or nutritional substances to the maternal vasculature becomes marginal. When the so-called maternal hemodynamic preservation threshold is reached, a pronounced and wide-spread vasodilation occurs to maintain adequate perfusion of maternal organs. The late-gestational decrease in BP thus reflects a dynamic interaction between the maternal and placental circulations rather than reflecting their passive combination. The hypothesis provides a framework for the integrated discussion of a number of important phenomena: the fact that hypertensive rats exhibit a larger decrease in BP in late gestation than normotensive rats; the existence of a positive association between litter size and the magnitude of the late-gestational decrease in BP; and, finally, the well-established ability of the food-restricted pregnant rat to compartmentalize its nutritional resources.
Fetal adrenal medulla catecholamine response to hypoxia-direct and neural components
Authors: Cheung C. Y.
Published: December 2017

In the fetus, the adrenal medullary catecholamine responses to hypoxia are mediated by direct and neural mechanisms. The present study determined the maturation of these responses in unanesthetized ovine fetuses from 109 to 136 days gestation. In intact fetuses at 109-119 days gestation, hypoxia lowered arterial PO2 from 23.4 +/- 0.9 to 9.5 +/- 0.4 mmHg and induced acute increases in plasma norepinephrine (P less than 10(-5)) and epinephrine (P less than 10(-5)) concentrations. Fetuses at 130-136 days gestation showed similar changes in PO2 and plasma catecholamines as in younger fetuses. Blockade of neural input to the adrenal by hexamethonium (25 mg/kg) reduced but did not eliminate the increases in plasma norepinephrine and epinephrine concentrations in fetuses at 109-119 days gestation, while it completely abolished these responses in fetuses at 130-136 days gestation. These results suggest that in unanesthetized ovine fetuses a direct response of the adrenal medulla to hypoxia is present at 110 days gestation. In contrast, at 130 days gestation the response to hypoxia is entirely neurally mediated. Thus neural innervation to the ovine fetal adrenal medulla matures before 110 days gestation, much earlier than previously reported.
Influence of temperature on muscle recruitment and muscle function in vivo
Authors: Rome L. C.
Published: December 2017

Temperature has a large influence on the maximum velocity of shortening (Vmax) and maximum power output of muscle (Q10 = 1.5-3). In some animals, maximum performance and maximum sustainable performance show large temperature sensitivities, because these parameters are dependent solely on mechanical power output of the muscles. The mechanics of locomotion (sarcomere length excursions and muscle-shortening velocities, V) at a given speed, however, are precisely the same at all temperatures. Animals compensate for the diminished power output of their muscles at low temperatures by compressing their recruitment order into a narrower range of locomotor speeds, that is, recruiting more muscle fibers and faster fiber types at a given speed. By examining V/Vmax, I calculate that fish at 10 degrees C must recruit 1.53-fold greater fiber cross section than at 20 degrees C. V/Vmax also appears to be an important design constraint in muscle. It sets the lowest V and the highest V over which a muscle can be used effectively. Because the Vmax of carp slow red muscle has a Q10 of 1.6 between 10 and 20 degrees C, the slow aerobic fibers can be used over a 1.6-fold greater range of swim speeds at the warmer temperature. In some species of fish, Vmax can be increased during thermal acclimation, enabling animals to swim at higher speeds.
Cerebral metabolic and hormonal activations during hemorrhage in sinoaortic-denervated rats
Authors: Kadekaro M. , Summy-Long J. Y. , Terrell M. L. , Lekan H. , Gary H. E. , Eisenberg H. M.
Published: December 2017

Denervation of sinoaortic baroreceptors in normovolemic rats selectively increases glucose utilization in the median eminence and pituitary neural lobe and enhances secretion of vasopressin and oxytocin. Hemorrhage in denervated animals increases further glucose metabolism in these structures and stimulates the release of both neurohypophysial hormones with preferentially a greater effect on vasopressin. Similar increases in glucose metabolism in these structures with a greater release of vasopressin are observed in sham-operated animals during hemorrhage. Absence of high-pressure receptors, therefore, does not modify the preferential release of vasopressin during hypovolemia. Hemorrhage also increases glucose utilization in the paraventricular and supraoptic nuclei, area postrema, and subfornical organ in sham-operated and denervated rats but only after a 20% blood reduction. The results indicate that decreased inputs from low-pressure receptors during hemorrhage increase the activity of the hypothalamoneurohypophysial system after small reductions in blood volume and that the activity of this system is tonically inhibited by baroreceptors. The activities of structures responsive to circulating angiotensin II (subfornical organ and area postrema) are stimulated by larger reductions in blood volume and their metabolic activities are not tonically influenced by high-pressure receptors.
Intrarenal atrial natriuretic peptide infusion lowers arterial pressure chronically
Authors: Hildebrandt D. A. , Mizelle H. L. , Brands M. W. , Gaillard C. A. , Smith M. J. , Hall J. E.
Published: December 2017

Chronic intravenous infusions of atrial natriuretic peptide (ANP) have been shown to lower mean arterial pressure (MAP) in both normal and hypertensive animals. However, the importance of the renal actions of ANP in mediating this hypotension is unknown. This study was designed to determine whether physiological or pathophysiological increases in intrarenal ANP levels influence long-term control of arterial pressure. ANP was infused into the renal artery of seven conscious, uninephrectomized, chronically instrumented dogs at 1, 2, and 4 ng.kg-1.min-1 for 7 days at each dose, followed by a recovery period. Then ANP was infused intravenously following the same protocol. MAP decreased from 88 +/- 3 to 78 +/- 3 mmHg during intrarenal infusion of 1 ng.kg-1.min-1 ANP; increasing the ANP infusion rate did not result in a further reduction in MAP. Systemic arterial plasma ANP concentration did not change from control (15 +/- 5 pg/ml) during 1 or 2 ng.kg-1.min-1 intrarenal ANP infusion but increased slightly during 4 ng.kg-1.min-1 intrarenal ANP infusion, averaging 53 +/- 11 pg/ml. Renal arterial plasma ANP concentrations were calculated to increase to approximately 120 +/- 5, 248 +/- 11, and 484 +/- 22 pg/ml during 1, 2, and 4 ng.kg-1.min-1 intrarenal ANP infusion, respectively. Intravenous ANP infusion did not alter MAP at 1 ng.kg-1.min-1, but MAP was slightly lower than control during 2 and 4 ng.kg-1.min-1 ANP infusion and remained below control during the postinfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)
Osmoresponsive units in sheep median preoptic nucleus
Authors: McAllen R. M. , Pennington G. L. , McKinley M. J.
Published: December 2017

Single-unit neural activity in the lamina terminalis, a region implicated in osmoregulation, was studied in alpha-chloralose-anesthetized sheep during mild hyperosmotic stimulation (intracarotid infusions of 1.65 M NaCl, 3 M sorbitol in 0.15 M NaCl, or 3 M urea in 0.15 M NaCl, at 1 ml/min). Twelve of 121 units (9.9%) were activated significantly (by 82 +/- 52%) by 2- to 3-min infusions of 1.65 M NaCl. Eleven of these and one untested unit were excited by hypertonic sorbitol (91 +/- 40% increase). Of five units further tested with urea, two were excited (by 19 and 58%). Isotonic or hypotonic NaCl infusions were without effect (eight osmoresponsive units tested). All responsive units were in the median preoptic nucleus (MnPO; nucleus medianus). MnPO units were compared with neurohypophysial fibers (multiunit recordings). Osmotic response profiles were similar; both MnPO units and neurohypophysial fibers responded equally to hypertonic NaCl and sorbitol but less to equiosmolal urea. Both MnPO units and neurohypophysial fibers responded slowly, taking 50 and 30 s of NaCl infusion, respectively, to show significant increases and approximately 2 min to reach peak activity. Their hemodynamic responses differed, however; neurohypophysial fibers were strongly excited by nitroprusside-induced hypotension (three of three animals) but MnPO osmoresponsive units were not (zero of five units). Osmoresponsive MnPO units may contribute osmotic, but not hemodynamic, inputs to control vasopressin secretion and/or osmoregulatory responses.
Decreased cerebral sodium concentration and sodium appetite in BALB/c mice
Authors: Osborne P. G. , Blair-West J. R. , Denton D. A. , McBurnie M. , Tarjan E. , Williams R. M. , Weisinger R. S.
Published: December 2017

BALB/c mice were allowed free access to water, food, and 0.3 M NaCl. Intracerebroventricular infusion of 0.7 M mannitol in artificial cerebrospinal fluid (CSF) was used to reduce CSF sodium concentration. The infusion was made at 24 microliters/day, which was similar on a body weight basis to the rate that evoked a large increase in sodium appetite in sheep. Reduction of CSF sodium concentration did not increase the voluntary sodium intake of sodium-replete mice or furosemide-treated, sodium-depleted mice. Thus, in contrast to findings in sheep and cattle and similar to the findings in the laboratory rat and wild rabbits, changes in cerebral sodium concentration are apparently not involved in the sodium appetite of mice.
Effects of stress and exercise on rat hippocampus and striatum extracellular lactate
Authors: De Bruin L. A. , Schasfoort E. M. , Steffens A. B. , Korf J.
Published: December 2017

Extracellular lactate was continuously monitored (lactography) to determine the effect of various stressors to assess glucose metabolism in the rat hippocampus and striatum. It appeared that immobilization, emotional stress, and exercise (physiological stress) all resulted in an increase in hippocampal extracellular lactate. Exercise had the most pronounced effect. These increases were different for rats raised in different laboratories. Only during exercise a transient increase in lactate was seen in striatum. Peripheral infusions of epinephrine and/or corticosterone did not affect the basal levels of hippocampal lactate. Adrenodemedullated rats showed an attenuated lactate increase compared with control rats during and shortly after exercise. Administration of ipsapirone, an anxiolytic drug, attenuated the stress-induced formation of the hippocampal lactate. The present study demonstrates the usefulness of lactography to monitor regional brain metabolism in freely moving animals, exposed to various stressors, breeding conditions, or drugs. The observed different responsiveness of the two brain-region studies emphasizes the different involvement of the striatum and hippocampus in motor and emotional behavior, respectively. Lactate formation is stimulated by excitatory neuronal activity, presumably originating in the cerebral cortex, although adrenal hormones appear to contribute.
Rostral ventrolateral medulla and sympathorespiratory integration in rats
Authors: Guyenet P. G. , Darnall R. A. , Riley T. A.
Published: December 2017

The respiratory modulation of the lumbar sympathetic nerve discharge (LSND) was examined in halothane-anesthetized, paralyzed, and vagotomized rats by means of phrenic nerve discharge (PND)-triggered histograms. The respiratory modulation was 1) proportional to PND amplitude during chemoreceptor activation with CO2 and 2) reduced at elevated arterial pressure. Bilateral injections of bicuculline [gamma-aminobutyric acid (GABA)A receptor antagonist, n = 5] into the rostral ventrolateral medulla (RVLM), but not into medullary raphe, reversibly increased mean arterial pressure (MAP) and resting LSND, decreased the baroreflex, reduced PND amplitude and central respiratory rate, and greatly magnified the respiratory modulation of LSND. Injections of strychnine (glycine receptor antagonist, n = 5) or phaclofen (GABAB receptor antagonist, n = 2) into RVLM were without effect. Injections of kynurenic acid (excitatory amino acid receptor antagonist) into RVLM (n = 8), but not raphe (n = 3), reduced PND amplitude, increased central respiratory rate, reduced MAP, elevated resting LSND slightly, and greatly reduced the respiratory modulation of LSND. These data suggest that the rostral tip of the ventrolateral medulla represents a critical link between the central respiratory rhythm generator and the vasomotor outflow. Also, it indicates that the respiratory modulation of SND does not involve a gating of the activity of the medullary neurons that convey baroreceptor information to RVLM sympathoexcitatory neurons.
Normalization of arterial pressure after barodenervation: role of pressure natriuresis
Authors: Osborn J. W. , England S. K.
Published: December 2017

Studies in several species have demonstrated that mean arterial pressure (MAP) is normal or only slightly elevated after chronic arterial baroreceptor denervation. We hypothesized that the absence of sustained hypertension after barodenervation was the result of a pressure natriuresis response, secondary to sympathetic vasoconstriction of nonrenal vasculature. To test this hypothesis, MAP, sodium balance (NaBal), and water balance were measured before and after aortic baroreceptor denervation (ABD), sinoaortic denervation (SAD), or sham surgery in conscious rats. MAP was increased 20.0 +/- 3.7 mmHg 1 day after ABD but returned to control by day 3. ABD had no significant effect on daily NaBal or water balance. The responses to SAD were similar to those after ABD, with the exception that a significant natriuresis was observed the first day after SAD. However, this was followed by a significant antinatriuresis on day 2, when MAP was still elevated. By day 3 after SAD, MAP, NaBal, and water balance were not significantly different from control. These results suggest that the normalization of MAP after ABD or SAD is not the result of pressure natriuresis but rather failure to maintain a chronic elevation of sympathetic activity after barodenervation.
Acute phase response in exercise: interaction of age and vitamin E on neutrophils and muscle enzyme release
Authors: Cannon J. G. , Orencole S. F. , Fielding R. A. , Meydani M. , Meydani S. N. , Fiatarone M. A. , Blumberg J. B. , Evans W. J.
Published: December 2017

everal host defense responses and metabolic reactions that occur during infection have been observed after exercise. We hypothesized that these reactions, known as the “acute phase response,” contribute to the breakdown and clearance of damaged tissue after exercise. This hypothesis was tested with 21 male volunteers representing two ranges of age (22-29 and 55-74 yr), who ran downhill on an inclined treadmill to accentuate damaging eccentric muscular contractions. The subject groups were further divided in a double-blind placebo-controlled protocol, which examined the influence of 48 days of dietary vitamin E supplementation before the exercise. All subjects were monitored for 12 days after exercise for changes in circulating leukocytes, superoxide release from neutrophils, lipid peroxidation, and efflux of the intramuscular enzyme creatine kinase (CK) into the circulation. Among those receiving placebo, the less than 30-yr-old subjects responded to exercise with a significantly greater neutrophilia and higher plasma CK concentrations than the greater than 55-yr-old subjects. Dietary supplementation with vitamin E tended to eliminate the differences between the two age groups, primarily by increasing the responses of the greater than 55-yr-old subjects. At the time of peak concentrations in the plasma, CK correlated significantly with superoxide release from neutrophils. The association of enzyme efflux with neutrophil mobilization and function supports the concept that neutrophils are involved in the delayed increase in muscle membrane permeability after damaging exercise.
Kidney function in ANF-transgenic mice: effect of blood volume expansion
Authors: Field L. J. , Veress A. T. , Steinhelper M. E. , Cochrane K. , Sonnenberg H.
Published: December 2017

Transgenic mice, created from inbred C3HeB/FeJ embryos, were used to overexpress selectively in the liver a fusion gene comprising mouse transthyretin (TTR) regulatory and atrial natriuretic factor (ANF) structural sequences. Animals were anesthetized, and kidney function was studied before and after blood volume expansion. Baseline urine volumes and electrolyte excretions were not significantly different from those of non-transgenic littermates, despite a markedly lower arterial blood pressure in the experimental group. A slightly lower glomerular filtration rate (GFR) in transgenics was not different statistically. Plasma ANF levels measured by radioimmunoassay were approximately 10-fold higher in the transgenic animals, compared with their nontransgenic siblings. After acute blood volume expansion, the diuretic, natriuretic, kaliuretic, and chloruretic responses were markedly enhanced in the transgenic group. Arterial pressure was increased as a result of hypervolemia, although it remained relatively depressed relative to the controls. GFR again was not different. We conclude that transgenic mice overexpressing ANF can maintain normal excretion of salt and water, possibly via ANF-induced reduction of renal perfusion pressure. After acute blood volume expansion, an increase in pressure may allow full renal expression of the chronically elevated ANF levels.
Topography of efferent vagal innervation of the rat gastrointestinal tract
Authors: Berthoud H. R. , Carlson N. R. , Powley T. L.
Published: December 2017

The gastrointestinal territories innervated by the gastric, celiac, and hepatic abdominal vagi were identified in rats with selective branch vagotomies by means of 1) anterograde tracing with the carbocyanine dye DiI injected into the dorsal motor nucleus and 2) measurement of cervical vagal stimulation-induced motility responses throughout the gut axis. Presence of DiI-labeled vagal terminals in the myenteric plexus and evoked motility responses were well correlated across the sampled gastrointestinal (GI) sites. In animals with only the two gastric branches intact, the entire stomach and the most proximal duodenum showed significant motility responses and were densely innervated, having DiI-labeled vagal terminals in almost every ganglion. The hepatic branch was found to primarily innervate the duodenum, with minor projections to the distal antral stomach and the intestines. The two celiac branches were found to almost exclusively innervate the jejunum, ileum, cecum and entire colon, and, together with the other vagal branches, the duodenum. Therefore, while there is some degree of specific innervation by the abdominal vagal branches of the oral-to-anal gut axis, which could be called "viscerotopic," the considerably overlapping innervation of the duodenum does not satisfy a viscerotopy criterion and needs further functional analysis.
High-potassium diet attenuates salt-induced acceleration of hypertension in SHR
Authors: Sato Y. , Ando K. , Ogata E. , Fujita T.
Published: December 2017

We studied the effects of K supplementation (8% KCl) for 4 wk on blood pressure (BP), Na space, and renal hemodynamics in 5-wk-old, spontaneously hypertensive rats (SHR) or age-matched Wistar-Kyoto rats (WKY) eating normal-NaCl (0.66%) or high-NaCl (8%) diet. In WKY, high-Na and/or high-K diets had no effects on BP. In SHR, Na load accelerated the development of hypertension, whereas K supplementation did not affect BP of normal-Na SHR but attenuated the increase in BP with Na load. Correspondingly, Na load in SHR significantly increased renal vascular resistance (RVR), and K supplementation attenuated the increased RVR of Na-loaded SHR. Moreover, Na space of SHR was increased compared with that of WKY, and although Na load did not affect Na space, K supplementation tended to decrease Na space in SHR. These results indicate that 9-wk-old SHR is relatively volume-expanded compared with age-matched WKY, and K supplementation could improve the lowered slope of the pressure-Na excretion relationship in SHR, resulting in maintenance of Na balance. Thus the data suggest that changes in RVR, which might be intimately related to renal function for Na excretion, contribute to both salt sensitivity of SHR and antihypertensive action of K supplementation in Na-loaded SHR.
Inhibitory renorenal reflexes: a role for substance P or other capsaicin-sensitive neurons
Authors: Kopp U. C. , Smith L. A.
Published: December 2017

In anesthetized rats, we examined whether inhibitory renorenal reflex responses to renal pelvic mechanoreceptor (MR) and chemoreceptor (CR) stimulation were mediated by substance P (SP)-containing neurons. Capsaicin (0.5 ng to 5 micrograms) injected into the renal pelvis increased afferent renal nerve activity (ARNA) dose dependently, from 60 +/- 19 to 333 +/- 105%. For a given ARNA response, a 100-fold higher dose was required when capsaicin was injected into the renal interstitium compared with the renal pelvis. Renal pelvic administration of SP (25 ng) increased ipsilateral ARNA by 126 +/- 34% and contralateral urine flow rate and urinary sodium excretion by 21 +/- 4 and 28 +/- 7%, respectively, a response similar to that produced by renal MR and CR stimulation. Mean arterial pressure was unaffected. Ipsilateral renal denervation abolished the contralateral diuresis and natriuresis produced by SP. In rats treated with capsaicin (950 mg/kg subcutaneously over 1 wk) to deplete sensory neurons of SP, renal MR and CR stimulation failed to elicit a renorenal reflex response. The data suggest that the renorenal reflex responses to renal MR and CR stimulation are mediated at least, in part, by SP neurons or other sensory neurons susceptible to depletion by capsaicin.
Chronic vs. acute hemodynamic effects of atrial natriuretic factor in conscious rats
Authors: Harrison-Bernard L. M. , Vari R. C. , Holleman W. H. , Trippodo N. C. , Barbee R. W.
Published: December 2017

The present study was designed to examine acute (2 h) and chronic (5 day) effects of pathophysiological elevations of plasma atrial natriuretic factor (ANF) in conscious normotensive rats. Acute infusion of ANF (100 ng.kg-1.min-1; n = 15) resulted in a decrease in mean arterial pressure (MAP) of 5 +/- 3 mmHg, which was associated with a 23 +/- 4% decrease in cardiac output (CO) and a 27 +/- 6% increase in total peripheral resistance (TPR). Hematocrit increased from 41.9 +/- 0.7 to 46.0 +/- 0.6%, which is suggestive of vascular volume contraction. Chronic infusion of ANF (n = 9) produced a significant fall in MAP from a control value of 114 +/- 2 to 100 +/- 3 and 99 +/- 2 mmHg on days 1 and 5, respectively. CO decreased significantly (27 +/- 2%) and TPR increased (21 +/- 5%) on day 1; neither variable was significantly different from control on day 5. Plasma immunoreactive ANF levels were significantly elevated during acute (791 +/- 76 pg/ml) and chronic (626 +/- 202 pg/ml) ANF infusion compared with control values of approximately 100 pg/ml. The results indicate that elevations in plasma ANF within the pathophysiological range can significantly alter systemic hemodynamics, initially mediated by a decrease in CO. Autoregulatory phenomena may counteract these hemodynamic effects, returning CO to control levels and reducing TPR when the elevations in plasma ANF are chronically sustained.
Renal and humoral responses to sustained cardiopulmonary baroreceptor deactivation in humans
Authors: Miller J. A. , Floras J. S. , Skorecki K. L. , Blendis L. M. , Logan A. G.
Published: December 2017

The renal and neurohumoral effects of prolonged cardiopulmonary baroreflex unloading and the relationship of these changes to urinary sodium excretion have not been well documented in humans. In this study, 12 normal males underwent lower body negative pressure at -15 mmHg for 90 min, a maneuver that deactivates cardiopulmonary baroreceptors. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction (FF) were measured in eight of these subjects using inulin and p-aminohippuric acid clearance techniques. During reduction of central venous pressure, arterial blood pressure and heart rate did not change. Plasma concentrations of atrial natriuretic factor (ANF) decreased markedly (22 +/- 2 to 12 +/- 1 pg/ml, P = 0.0001) as did the second messenger of ANF's biological action, guanosine 3',5'-cyclic monophosphate, whereas renin and vasopressin were not significantly altered. There was a significant rise in plasma norepinephrine (1.6 +/- 0.2 to 2.4 +/- 0.4 nmol/l, P = 0.03). GFR (104 +/- 9 to 68 +/- 6 ml/min, P = 0.007) and FF (0.18 +/- 0.01 to 0.14 +/- 0.01, P = 0.007) decreased significantly, with maintenance of ERPF. There was a significant antinatriuresis without an antikaliuresis and a significant reduction in free water clearance. These changes in renal hemodynamics are unlike the known effects of renal vasoconstrictors, and the alterations in solute and free water clearance are consistent with the removal of the known actions of ANF from tubular target sites. Taken together, our findings suggest that a mechanism other than activation of vasoconstrictors, possibly the diminution of the influence of ANF on the kidney, may be operative in the renal adjustments to cardiopulmonary baroreflex deactivation in humans.
Effect of a soup preload on reduction of food intake by cholecystokinin in humans
Authors: Muurahainen N. E. , Kissileff H. R. , Lachaussee J. , Pi-Sunyer F. X.
Published: December 2017

Cholecystokinin octapeptide (CCK-8) or saline was intravenously infused for 5 min before and 5 min during a meal of macaroni and beef, served 20 min after a preload of either 100 or 500 g of soup to 12 nonobese men. Intake of the test meal was significantly lower when CCK-8 was given, following the larger preload, than after any of the other treatments. There were no significant differences among the other three treatment conditions. These results are consistent with the hypothesis that gastric, but not merely pregastric, stimulation interacts with CCK-8 to reduce food intake in humans. Although gastric filling seems to be the most likely stimulus for the interactive effect with CCK-8, other factors such as activation of nutrient-sensitive sites cannot be eliminated. In addition, hunger ratings were significantly lower immediately after the larger soup preloads than after the smaller. Hunger ratings after the soup also correlated better with test-meal intake after the large soup preloads with and without CCK-8 than after the smaller preloads. Hunger did not correlate significantly with test meal intake after the small soup preload with CCK-8. These results suggest that hunger ratings are more sensitive predictors of intake when the stomach is relatively full (i.e., after a large preload) than when it is relatively empty (i.e., after a small preload) at the time the hunger rating is taken.
Fourth ventricular capsaicin attenuates suppression of sham feeding induced by intestinal nutrients
Authors: Yox D. P. , Stokesberry H. , Ritter R. C.
Published: December 2017

Systemic treatment with capsaicin, a neurotoxin that destroys small unmyelinated primary sensory neurons, causes degeneration of vagal sensory fibers and attenuates suppression of sham feeding by exogenous cholecystokinin (CCK) or intraintestinally infused nutrients. To determine whether capsaicin-sensitive neurons or fibers in the hindbrain mediate suppression of feeding by intestinal nutrients, we examined nutrient-induced suppression of sham feeding in rats pretreated with fourth ventricular capsaicin. Capsaicin treatment abolished the suppression of sham feeding induced by intraperitoneal injection of CCK octapeptide or by intraintestinal maltose. Oleate-induced suppression of sham feeding also was significantly attenuated in capsaicin-treated rats. Capsaicin treatment, however, did not attenuate suppression of sham feeding by intraintestinal L-phenylalanine. These results indicate that capsaicin-sensitive substrates, located near the fourth ventricle, participate in the suppression of sham feeding by CCK and by some intestinal stimuli. Taken together with previously reported data, these results suggest that suppression of sham feeding by some intestinal nutrients is mediated by a neuronal substrate similar or identical to one that mediates suppression of feeding by exogenous CCK.
Influence of air temperature on ventilation rates and thermoregulation of a flying bat
Authors: Thomas S. P. , Follette D. B. , Farabaugh A. T.
Published: December 2017

To assess the involvement of the ventilatory system in thermoregulation during flight, breathing frequencies and tidal volumes were measured from three Phyllostomus hastatus undertaking steady wind tunnel flights at a constant speed over a range of air temperatures (Ta) from 17.7 to 31.1 degrees C. Mean breathing frequency was independent of Ta, and tidal volume increased only modestly with increasing Ta. Consequently, minute ventilation rate increased insignificantly over the range of Ta values investigated. Mean rectal temperature showed a direct linear relation to Ta and increased significantly from 39.1 to 41.9 degrees C over the range of Ta values investigated. The highest rectal temperatures measured from flying P. hastatus are approximately 3 degrees C less than those of flying birds. In contrast to flying birds, flying P. hastatus does not modulate its rate of respiratory evaporative heat loss to any significant extent in response to environmental heat stress and only loses an estimated 14% of its metabolic heat load by this route. Cutaneous heat loss channels must therefore be very important to these animals. Some reasons for the observed differences in the thermoregulatory responses of flying bats and birds are discussed as well as the relative advantages and limitations of each group's solutions to their thermoregulatory challenges.
Attentuation of systemic vasoreactivity in chronically hypoxic rats
Authors: Doyle M. P. , Walker B. R.
Published: December 2017

Experiments were performed to assess the effects of chronic hypoxia on systemic vasoreactivity in conscious unrestrained rats and in abdominal aortic rings. Two groups of rats were used: normoxic controls and chronically hypoxic rats that were maintained in a hypobaric chamber (380 mmHg) for 4 wk before experimentation. In conscious animals instrumented with pulsed Doppler cardiac output probes and arterial and venous catheters, mean arterial pressure and mean cardiac output were measured before and during graded continuous infusions of phenylephrine (PE), angiotensin II, and arginine vasopressin (AVP). Measurements were made while the animals breathed either room air or 12% O2. Acute exposure to 12% O2 significantly reduced pressor and vasoconstrictor responses for all three agents. These responses were also attenuated in the chronically hypoxic rats in 12% O2; however, acute return to room air conditions did not return pressor or vasoconstrictor responses to normoxic control levels. In abdominal aortic rings from both groups of animals, cumulative dose-response curves to PE and AVP were completed in 21 and 3% O2 conditions. Neither acute nor chronic hypoxia caused a shift in the dose-response curves. In rings from control rats, maximum tension responses to AVP were significantly diminished in 3% O2. Rings from chronically hypoxic rats exhibited less maximum tension to AVP in 21% O2 than did rings from control rats. We conclude that acute hypoxia reversibly attenuates systemic vasoreactivity and that chronic hypoxia induces a more sustained decrease in reactivity. In addition, at least part of the mechanism may reside within the vasculature.
Brown fat-specific mitochondrial uncoupling protein in adipose tissues of newborn reindeer
Authors: Soppela P. , Nieminen M. , Saarela S. , Keith J. S. , Morrison J. N. , Macfarlane F. , Trayhurn P.
Published: December 2017

Reindeer inhabit a severe arctic or subarctic environment, with the young born in early spring under adverse weather conditions. The extreme northern climate imposes a major thermal challenge to the newborn, and in the present study we have examined fetal, neonatal, and young (from 2 wk before birth to 16 mo postpartum) semidomesticated reindeer from northern Finland for the presence of thermogenic brown adipose tissue. Adipose tissues were removed, mitochondria were prepared, and the proteins were separated by molecular weight and blotted onto nitrocellulose membranes. The membranes were then probed for the presence of the 32,000-relative molecular weight mitochondrial uncoupling protein (UCP) unique to brown fat by use of a rabbit anti-(ground squirrel UCP) serum. Immunoreactivity at the molecular weight characteristic of UCP was present in perirenal, abdominal, inter(pre)scapular, sternal, intralumbar, vertebral, tracheal, inguinal, and omental-mesenteral adipose tissues of newborn reindeer (0-2 days of age). No immunoreactivity was detected in coronary adipose tissue. UCP was found at high levels in interscapular and perirenal adipose tissues of fetal reindeer at 2 wk before birth. Although the protein was present during the first few days postpartum, little immunoreactivity was found at 1 mo of age, and none was evident by 2 mo. UCP and its mRNA were also apparent in perirenal adipose tissue of the newborn of another species of Cervidae, the red deer. It is concluded, on the basis of the immunologic identification of UCP, that most adipose tissues of newborn reindeer represent functional brown fat but that there is a subsequent conversion to white adipose tissue by the 2nd mo of life.(ABSTRACT TRUNCATED AT 250 WORDS)
Carrier-mediated mechanism for biotin transport in rabbit intestine: studies with brush-border membrane vesicles
Authors: Said H. M. , Derweesh I.
Published: December 2017

Simple diffusion has been reported as the mechanism of biotin transport in rabbit intestine. In this study, we reevaluated this concept by examining biotin transport in rabbit intestine using optimal experimental conditions and a well-established brush-border membrane vesicles (BBMV) technique. Uptake of biotin by rabbit intestinal BBMV was found by an osmolarity study to be mostly the result of transport of the vitamin into an osmotically sensitive intravesicular space with little binding to membrane surfaces. Biotin transport in rabbit intestinal BBMV was 1) Na+ gradient dependent (out greater than in) with a clear “overshoot” phenomenon, indicating the accumulation of the substrate against a concentration gradient; 2) initial rate of biotin transport by the Na+ gradient-dependent component was saturable as a function of substrate concentration with apparent Km and maximum velocity (Vmax) values of 6.7 microM and 10.7 pmol.mg protein-1 x 10 s-1, respectively; 3) inhibited by high concentrations of unlabeled biotin and its related compounds desthiobiotin and thioctic acid in the presence, but not absence, of a Na+ gradient; and 4) not affected by inducing a relatively positive or negative intravesicular space with the use of valinomycin-induced K+ diffusion potential. These findings indicate that the biotin transport mechanism in rabbit intestine is carrier mediated in nature. Furthermore, this mechanism is Na+ gradient dependent, capable of accumulating the substrate against a concentration gradient and transport the vitamin via an electroneutral process.
Endothelium-derived relaxing factor in regulation of basal cardiopulmonary and renal function
Authors: Perrella M. A. , Hildebrand F. L. , Margulies K. B. , Burnett J. C.
Published: December 2017

The endothelium has emerged as an important modulator of vascular tone by producing both vasodilating and vasoconstricting substances. In vitro studies have demonstrated that endothelial cells produce endothelium-derived relaxing factor (EDRF), which promotes vasodilation via the stimulation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). However, the role of EDRF in the basal regulation of cardiopulmonary and renal function is not well defined. The present study was therefore designed to assess the function of EDRF by studying two groups of normal anesthetized dogs, of which one received a competitive inhibitor to EDRF generation, NG-monomethyl-L-arginine (L-NMMA; 50 micrograms.kg-1.min-1 iv), and the other received a vehicle. The L-NMMA infusion produced no significant increase in mean arterial pressure but marked increases in systemic, pulmonary, and renal vascular resistances compared with the vehicle group. Although renal blood flow decreased with L-NMMA, no changes were observed in glomerular filtration rate or sodium excretion. Associated with the cardiopulmonary and renal responses with L-NMMA was a modest increase in plasma endothelin (7.9 +/- 1.3 to 10.2 +/- 1.8 pg/ml, P less than 0.05), an endothelium-derived vasoconstrictor. No alteration was observed in plasma or urinary cGMP with EDRF inhibition. These cardiopulmonary and renal responses with L-NMMA may be attributed not only to EDRF inhibition but to an imbalance between endothelium-derived relaxing and contracting factors.