bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of median eminence lesion on the hypertensive response due to acute aortic coarctation
Authors: Fregoneze J. B. , Salgado M. C. , Salgado H. C.
Published: December 2017

The present study was designed to investigate the effect of a lack of vasopressin resulting from electrolytic lesion of the median eminence of the hypothalamus on the acute 45-min aortic coarctation hypertension elicited in conscious rats by means of a pneumatic cuff placed around the aorta above the renal arteries. Forty-eight hours after lesion, aortic constriction elicited a prompt (5-min) rise in mean carotid pressure from 115 +/- 2 to 149 +/- 2 mmHg, followed by a gradual decline to 129 +/- 2 mmHg. In contrast, sham-lesioned rats exhibited a prompt hypertensive response from 118 +/- 2 to 157 +/- 2 mmHg that leveled off throughout the experiment. Lesioned rats treated with saralasin presented a blunted hypertensive response (within 125 +/- 2 to 130 +/- 2 mmHg), whereas sham-lesioned rats showed only a delay in the onset of hypertension. The hypertensive response of lesioned rats was unaffected by the vasopressin antagonist [d(CH2)5Tyr(Me)]AVP, whereas sham-lesioned rats submitted to this treatment presented a prompt rise in pressure followed by a gradual decline at the end of the experiment. Lesioned and sham-lesioned rats treated with saralasin plus vasopressin antagonist showed a blunted hypertensive response throughout the experiment. These data demonstrate that the integrity of the median eminence plays a pivotal role in the maintenance (30-45 min) of acute aortic coarctation hypertension, presumably involving the release of vasopressin from the neurohypophysis, whereas angiotensin II mainly accounts for the prompt (5-15 min) rise in pressure.
Effect of atrial natriuretic factor on release of arginine vasopressin and renin in fetal lambs
Authors: Berry D. D. , Jaekle R. K. , Rose J. C.
Published: December 2017

The purpose of this study was to determine the effect of increased plasma atrial natriuretic factor (ANF) concentrations on the arginine vasopressin (AVP) and renin response to arterial hypotension in fetal sheep. Lamb fetuses at 123-133 days of gestation were infused intravascularly with 0.9% NaCl and ANF at 25 ng.kg-1.min-1 (low dose) or NaCl and ANF at 250 ng.kg-1.min-1 (high dose) for 115 min. After 45 min, sodium nitroprusside was infused for 10 min to yield a 25% decrease in mean arterial blood pressure. ANF infusions resulted in plasma concentrations of 150-200 and 500-800 pg/ml in the low-dose and high-dose groups, respectively. In both the low-dose and high-dose ANF groups, AVP and renin concentrations increased in response to hypotension. In the low-dose ANF group, there was no difference in this response between ANF and control lambs. Compared with controls, a high dose of ANF resulted in an elevated basal level of AVP (1.6 +/- 0.04 vs. 12.3 +/- 6.7 pg/ml) and an 11-fold increase of AVP at 10 min of hypotension (12.2 +/- 5.6 vs. 134.9 +/- 36.1 pg/ml). Basal and stimulated renin concentrations were unchanged by the high-dose ANF infusion. This study demonstrates that in the fetal lamb, ANF concentrations of 500-800 pg/ml augment the basal and stimulated release of AVP but do not affect the renin response.
Ontogenic changes in renal response to alpha 1-adrenoceptor stimulation in sheep
Authors: Guillery E. N. , Segar J. L. , Merrill D. C. , Nakamura K. T. , Jose P. A. , Robillard J. E.
Published: December 2017

The present study was designed to examine the effect of direct intrarenal infusion of the alpha 1-adrenoceptor agonist, phenylephrine, on urinary flow rate (UFR) and on renal Na and Cl excretion in conscious and chronically instrumented fetal (128-133 days gestation, term 145 days), newborn (6-12 days), and adult sheep. Five different renal concentrations of phenylephrine, varying from 5 +/- 1 to 72 +/- 2 ng/ml, were studied. Low renal phenylephrine concentration (< or = 12 +/- 1 ng/ml) induced a significant renal vasoconstrictor response in fetuses but not in newborn and adult sheep. The effects of intrarenal phenylephrine infusion on UFR and fractional excretion of Na (FENa) was greater (P < 0.05) in newborn lambs than in fetal and adult sheep. At a renal concentration of phenylephrine between 9 +/- 1 and 12 +/- 1 ng/ml, the percent decrease in UFR was greater (P < 0.05) in newborn lambs (-19.1 +/- 4.7%) than in fetal (9.8 +/- 8.9%) and adult sheep (-3.3 +/- 3.9). The percent decrease in FENa at renal concentration of phenylephrine between 18 +/- 1 and 24 +/- 1 ng/ml was also significantly (P < 0.05) larger in newborn lambs (-20.2 +/- 2.8%) than in fetal (-8.0 +/- 3.1%) and adult sheep (-11.2 +/- 2.6%). In summary, the present results indicate that the fetal kidney has a limited ability to increase sodium reabsorption in response to stimulation of alpha-adrenoceptors and that the effect of renal alpha-adrenoceptor stimulation on urinary volume and urinary sodium excretion increases during the newborn period.
Muscle glucose utilization during sustained swimming in the carp (Cyprinus carpio)
Authors: West T. G. , Brauner C. J. , Hochachka P. W.
Published: December 2017

The involvement of circulatory glucose in the energy provision of skeletal muscle and heart of swimming carp was examined. Plasma glucose concentration varied from 3 to 17 mM among individual carp, and estimates of glucose turnover rate (RT) were positively correlated with plasma glucose level in resting fish (range 1.6-6.3 mumol.min-1.kg-1) and in swimming fish (range 4.2-10.7 mumol.min-1.kg-1). Carp that were exercised at 80% of their critical swimming speed displayed a twofold higher RT at any given plasma glucose concentration. Metabolic clearance rate also doubled in swimming carp (1.0 +/- 0.1 ml.min-1.kg-1) relative to resting controls (0.5 +/- 0.1 ml.min-1.kg-1). Indexes of muscle glucose utilization (GUI), determined with 2-deoxy-D-[14C]glucose, indicated that glucose utilization in red muscle was not dependent on plasma glucose concentration; however, glucose utilization in this muscle mass was threefold higher in swimming fish than in resting control fish. On the basis of whole body aerobic scope measurements in carp, it was estimated that circulatory glucose potentially comprised 25-30% of the total fuel oxidation in the active red muscle mass. GUI in heart was positively correlated with plasma glucose concentration, and it is possible that glucose availability had considerable influence on the pattern of myocardial substrate oxidation in resting and active carp. Carp are somewhat more reliant than rainbow trout on glucose for locomotor energetics, correlating with species differences in swimming capability and with the greater capacity of omnivorous carp to tolerate dietary glucose.
Thermoregulatory responses to hyperinsulinemic hypoglycemia and euglycemia in humans
Authors: Maggs D. G. , Scott A. R. , MacDonald I. A.
Published: December 2017

Hypoglycemia induces physiological changes that influence thermoregulatory mechanisms. We studied such responses in a group of healthy males (mean age 23.5 yr, body mass index 23.7 kg/m2) during hyperinsulinemic euglycemia (E; 4.5 mmol/l) and hypoglycemia (H; 2.5 mmol/l) and under placebo control conditions (P; saline). Plasma epinephrine (P < 0.0001) and norepinephrine (P < 0.01) levels increased during H and were unchanged during P and E. During H, early increases in metabolic rate (P < 0.05), forearm blood flow (P < 0.01), and sweating (P < 0.01) were followed by a fall in skin temperature (from -1.2 to -2.6 degrees C) and blood flow (P < 0.01). Core temperature fell after 40 min of H and continued to fall thereafter (-0.34 +/- 0.08 degrees C). E and P had minimal effect on skin temperature and blood flow. In summary, in healthy human subjects, H causes a fall in core temperature by heat dissipation at the skin surface through evaporative heat loss and conduction of heat to the periphery, despite an increase in metabolic heat production.
Chronic physiological increases in cortisol inhibit the vasopressin response to hypertonicity in conscious dogs
Authors: Papanek P. E. , Raff H.
Published: December 2017

Chronic increases in cortisol inhibit basal plasma arginine vasopressin (AVP). Acute pretreatment with cortisol inhibits the large increase in AVP during hypotension or hypoxia but does not inhibit the modest increase in AVP in response to hypertonic saline (HS). We evaluated the effect of a chronic increase in cortisol (physiological range) on the acute AVP response to HS. Five male dogs received a continuous infusion of either vehicle or cortisol (65 mg/day) for 7 days. The AVP response to HS (0.2 mmol.kg-1.min-1 for 30 min) was tested before infusion, on days 1, 4, and 7 of chronic infusion, and 2 days after the infusion was discontinued. Plasma cortisol increased significantly from 1.0 +/- 0.2 micrograms/dl to an average over the 7 days of infusion of 5.0 +/- 0.2 micrograms/dl, and basal plasma AVP was significantly decreased during cortisol infusion. The increase in plasma Na and osmolality during HS was unaffected by chronic infusion. HS resulted in an increase in AVP from 3.5 +/- 0.2 to 7.1 +/- 0.7 pg/ml before cortisol infusion. After 7 days of cortisol, the AVP response to HS (from 2.6 +/- 0.1 to 3.9 +/- 0.7 pg/ml) was significantly attenuated. Sustained, physiological increases in cortisol significantly inhibited osmotically stimulated AVP release. The decrease in AVP during hypercortisolism and the syndrome of inappropriate antidiuretic hormone in patients with adrenal insufficiency appear to be due to an inhibitory effect of cortisol on the osmotic sensitivity of the AVP control system.
Hemodynamic response to vasopressin during V1-receptor antagonism in baroreflex-deficient subjects
Authors: Huch K. M. , Runyan K. R. , Wall B. M. , Gavras H. , Cooke C. R.
Published: December 2017

Six quadriplegic subjects and 6 control subjects received high-dose arginine vasopressin (AVP) infusions at rates of 500, 1,000, 2,000, and 4,000 microU.kg-1.min-1 in consecutive 10-min intervals. Six additional quadriplegic subjects received low-dose AVP infusions at rates of 50, 100, 200, 400, and 800 microU.kg-1.min-1. All subjects were studied once with and once without administration of a selective V1-receptor antagonist. During high-dose AVP infusions without V1-receptor blockade, mean arterial pressure (MAP) increased from 80 +/- 4 to 87 +/- 5 mmHg (P < 0.05) in quadriplegic subjects but was unchanged in control subjects. In the presence of V1-receptor blockade, MAP decreased from 75 +/- 4 to 58 +/- 4 mmHg (P < 0.001), and heart rate (HR) increased from 61 +/- 5 to 80 +/- 5 beats/min (P < 0.001) in quadriplegic subjects. In the studies on control subjects, MAP decreased only from 75 +/- 3 to 72 +/- 5 mmHg (P < 0.05), whereas HR increased from 64 +/- 4 to 87 +/- 4 beats/min (P < 0.001). Plasma renin activity (PRA) increased in both quadriplegic and control subjects. The effects of low-dose AVP infusions on MAP, HR, and PRA in quadriplegic subjects were similar to those observed during high-dose infusions. Thus, in the absence of baroreceptor-mediated sympathetic nervous system responses, a vasodilatory effect of AVP that is capable of producing marked reductions in MAP can be demonstrated in the presence of V1-receptor blockade.
Whole body energy expenditure and fuel oxidation after 2,5-anhydro-D-mannitol administration
Authors: Park C. R. , Seeley R. J. , Benthem L. , Friedman M. I. , Woods S. C.
Published: December 2017

The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) increases food intake in nondeprived rats. Several lines of evidence indicate that vagal signals arising from the liver are critical for this effect. In addition, 2,5-AM decreases plasma glucose and increases lipolysis, resulting in an increase in plasma free fatty acids and ketone bodies. In these respects 2,5-AM produces a state analogous to that observed after food deprivation. Using an indirect calorimeter, we determined that 2,5-AM (300 mg/kg ip) causes a potent and long-lasting decrease in respiratory quotient, indicating a decrease in the fraction of total energy derived from carbohydrate oxidation and an increase in the fraction derived from fatty acid oxidation. These metabolic variables were altered without affecting total metabolic rate. This dose of analogue also stimulated significantly greater food intake than injections of vehicle. These results support the continued use of 2,5-AM as a tool to probe the metabolic controls of food intake.
Pressor-induced responses of the cat ventral medullary surface
Authors: Harper R. M. , Gozal D. , Aljadeff G. , Carroll J. L. , Dong X. W. , Rector D. M.
Published: December 2017

We examined ventral medullary surface activity using light reflectance procedures after blood pressure alterations induced by phenylephrine or sodium nitroprusside in 23 pentobarbital sodium-anesthetized cats. Images of reflected 660-nm light were collected and digitized at 1- to 3-s intervals after baseline and intravenous saline, 5-40 micrograms/kg phenylephrine, or sodium nitroprusside infusion. Carotid sinus nerve denervation (CSD) and bilateral vagotomy were performed in five and three animals, respectively, and challenges were repeated. Phenylephrine elicited a dose-dependent transient blood pressure elevation and reflectance increase (interpreted as activity decline) over the entire ventral medullary surface examined. The increase consisted of an initial rapid transient component, peaking at 45 s, and a 3- to 5-min recovery. CSD enhanced, and vagotomy substantially reduced, the initial transient response to phenylephrine. Sodium nitroprusside-induced lowering of blood pressure was associated with decreased reflectance in rostral sites and increased reflectance in caudal regions. CSD abolished a late component and diminished amplitude of an initial rapidly rising component of changes induced by nitroprusside, a decline further accentuated by addition of vagotomy.
Regulatory volume decrease in lamprey erythrocytes: mechanisms of K+ and Cl- loss
Authors: Virkki L. V. , Nikinmaa M.
Published: December 2017

The nature of the swelling-activated K+ and Cl- transport pathways of lamprey (Lampetra fluviatilis) erythrocytes was studied. In isosmotic medium, unidirectional K+ and Cl- effluxes appear to be largely mediated by conductive pathways. Unidirectional Cl- efflux increased as a function of a decrease in medium osmolarity. The swelling-activated Cl- transport was inhibited by R(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inde n-5- yl)oxy]acetic acid (DIOA), furosemide, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In contrast, moderate cell swelling did not increase unidirectional ouabain-insensitive K+ efflux. However, inhibition of transport by Ba2+ was markedly reduced. This suggests that the Ba(2+)-sensitive pathway that mediated most of the K+ efflux in isosmotic conditions was inhibited by cell swelling and a Ba(2+)-insensitive pathway was activated. DIOA had no effect on K+ efflux in isosmotic or hyposmotic medium. These data and the finding that substitution of NO3- or SCN- for Cl- had only a minor effect on the swelling-induced net extrusion of K+ and water indicate that the pathways for K+ and Cl-, activated by cell swelling, are conductive.
Characterization of the endogenous intestinal peptide that stimulates the rectal gland of Scyliorhinus canicula
Authors: Anderson W. G. , Conlon J. M. , Hazon N.
Published: December 2017

It has been postulated that gut peptides play a major role in the regulation of rectal gland secretion in elasmobranchs. An isolated perfused rectal gland secretion in elasmobranchs. An isolated perfused rectal gland preparation was developed for Scyliorhinus canicula that responded to dibutyryl 3',5'-cyclic monophosphate plus 3-isobutyl-1-methylxanthine, increasing chloride clearance rates threefold over basal levels. Activity was stimulated by an endogenous peptide, isolated in pur form by reverse-phase high-performance liquid chromatography from the intestine of S. canicula. The primary structure was established as Ser-Pro-Ser-Asn-Ser-Lys-Cys-Pro-Asp-Gly-Pro-Asp-Cys-Phe-Val-Gly-Leu-Met- NH2. This is a sequence identical to that of the tachykinin scyliorhinin II. Perfusion of synthetic scyliorhinin II increased secretion rate in the rectal gland of S. canicula in a dose-dependent manner with a maximal response at 10(-6) M, whereas vasoactive intestinal peptide, a stimulator in the spiny dogfish, Squalus acanthias, had no effect. We propose that scyliorhinin II is the uncharacterized peptide rectin, previously identified from the intestine of S. canicula.
Correlation between neural release of VIP and adrenomedullary catecholamine secretion in vivo
Authors: Gaspo R. , Yamaguchi N. , de Champlain J.
Published: December 2017

The aim of the present study was to determine whether vasoactive intestinal peptide (VIP) can be released along with catecholamines from the adrenal gland in response to direct splanchnic nerve stimulation in anesthetized dogs. An attempt was made to verify whether VIP was released mainly from chromaffin cells or from the splanchnic nerve terminals. The first group received a supramaximal stimulation (12 V) given on the left splanchnic nerve at three successive frequencies of 0.2, 2, and 20 Hz. The second group received increasing doses of 1,1-dimethyl-4-phenylpiperazinium (DMPP) locally infused into the denervated left adrenal gland. In response to nerve stimulation, adrenal venous catecholamine concentration significantly increased in a frequency-dependent manner, whereas VIP-like immunoreactive substance (VIP-ir) reached a significant level only at the highest frequency. The multiple linear regression analyses revealed that the net increases in adrenal venous catecholamine concentrations were strongly correlated with combined variables of VIP-ir concentration and frequencies, indicating r = 0.915 and 0.949 (n = 42, P < 0.0001) for epinephrine and norepinephrine concentrations, respectively. In response to local DMPP infusion, adrenal venous catecholamines increased in a dose-dependent manner, whereas VIP-ir remained unchanged. The results indicate that VIP-ir is released along with catecholamines from the dog adrenal gland in response to direct splanchnic nerve stimulation in vivo. The study also suggests that VIP is mainly released from splanchnic nerve endings.
Inhibitory effect of atrial natriuretic factor on sympathetic ganglionic neurotransmission in humans
Authors: Floras J. S.
Published: December 2017

I have previously documented an inhibitory effect of atrial natriuretic factor (ANF) on postganglionic muscle sympathetic nerve activity (MSNA) in normal subjects that was consistent with either a central or ganglionic sympathoinhibitory action. To test the latter hypothesis, I examined, in seven young normotensive men, the effect of saline (as vehicle) and ANF (50 micrograms, then 50 ng.kg-1.min-1), given on 2 separate days according to a random double-blind study design, on blood pressure, heart rate, and MSNA before and after ganglionic neurotransmission was stimulated with edrophonium (ED; 12 mg iv), a rapidly reversible acetylcholinesterase inhibitor without central nervous system effects, and during subsequent augmentation of central sympathetic outflow by a cold pressor test (CPT). In five of these subjects, the protocol was replicated during nitroprusside infusion (0.4 micrograms.kg-1.min-1). ED increased MSNA during vehicle (P < 0.005) and nitroprusside (P < 0.003) but not during ANF infusion. The sympathoneural response to the combined stimuli of ED and CPT was also attenuated by ANF compared with either saline or nitroprusside infusions. Conclusions were that 1) postganglionic MSNA is increased by ED, 2) this facilitative effect of ED is attenuated by ANF, and 3) modulation of ganglionic neurotransmission is one mechanism for the relative sympatho-inhibition observed when ANF is infused at this dose.
Lymphatic regulation of hematocrit during hypoxia in the toad Bufo woodhousei
Authors: Malvin G. M. , Macias S. , Sanchez M. , Dasalla R. , Park A. , Duran M.
Published: December 2017

Hypoxia rapidly increases hematocrit (Hct) in anuran amphibians by reducing plasma volume, but the mechanism(s) mediating this response is unknown. We tested the hypothesis that, during hypoxia, plasma volume is reduced by impaired lymph heart (LH) function, decreasing lymph flow into the circulation. In Bufo woodhousei, we measured the effects of hypoxia on Hct, lymph heart rate (LHR), LH pressure, the movement of dye from the dorsal lymph sac to the arterial blood, and flow through an open LH cannula. We also tested whether splenic contraction or cholinergic nerves contribute to the hypoxia-induced changes. Graded hypoxia between 21 and 4% O2 produced graded increases in Hct (P < 0.0001) and decreases in LHR (P = 0.01). Hypoxia reduced the rate of increase in arterial Evans blue concentration after injection into the dorsal lymph sac (P = 0.041) and decreased flow through an open LH cannula (P < 0.012). Hypoxia increased Hct and reduced LHR similarly in control, splenectomized, and sham-splenectomized toads. Atropine had no significant effect on Hct and LHR. These results indicate that the LHs play a regulatory role in hypoxia-induced hemoconcentration.
EGTA-induced disruption of epithelial cell tight junctions in the lactating caprine mammary gland
Authors: Stelwagen K. , Farr V. C. , Davis S. R. , Prosser C. G.
Published: December 2017

The suitability of the Ca2+ chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to induce disruption of mammary tight junctions (TJ) and its effect on milk secretion were investigated in six goats. EGTA was administered via the teat of one gland as an isosmotic (300 mosmol/l) K-EGTA solution (68 mM EGTA), whereas the control gland received an isosmotic sucrose solution. Lactose, Na, K, and Cl in milk, blood lactose, and the presence of Evans blue (EB) in mammary lymph were used as indicators of TJ disruption. EGTA caused transient (approximately 60 h) changes (P < 0.05) in the concentration of lactose, K, Na, and Cl in milk, consistent with loss of TJ integrity. This was confirmed by a rapid (< 1 h) increase (P < 0.05) in blood lactose levels. Moreover, EB appeared in lymph < 1 h after EGTA+EB treatment. Milk secretion declined unilaterally by 15% (P < 0.05) after EGTA and did not return to baseline until approximately 60 h after EGTA. EGTA caused a unilateral, temporary (first 7 h) increase in mammary blood flow. This study shows that a rapid temporary disruption of mammary TJ can be successfully induced in vivo and that such disruption compromises milk secretion.
Angiotensin II modulates arterial baroreflex function via a central alpha 1-adrenoceptor mechanism in rabbits
Authors: Nishida Y. , Ryan K. L. , Bishop V. S.
Published: December 2017

To test the hypothesis that angiotensin II (ANG II) modulates arterial baroreflex function via a central alpha 1-adrenoceptor mechanism, we examined the effects of intravertebral infusion of ANG II on baroreflex function curves before and after intravertebral administration of the alpha 1-adrenoreceptor antagonist prazosin. Rabbits were chronically instrumented with subclavian and vertebral arterial catheters, venous catheters, and aortic and vena caval occludes. Baroreflex curves were obtained by relating heart rate (HR) to mean arterial pressure during increases and decreases in arterial pressure. Intravertebral infusions of ANG II (5, 10, and 20 ng.kg-1.min-1) produced a dose-dependent shift of the midrange of the curve toward higher pressures (64 +/- 1 to 68 +/- 1, 76 +/- 1, and 85 +/- 2 mmHg, respectively). Pretreatment with prazosin (10 micrograms/kg) via the vertebral artery markedly reduced the shift in the baroreflex curve induced by the highest dose of ANG II (64 +/- 2 to 70 +/- 2 mmHg). These data suggest that ANG II resets the operating point of the HR baroreflex curve to a higher blood pressure and that this effect is mediated via a central alpha 1 mechanism. When the effects of vertebral ANG II on the baroreflex control of renal sympathetic nerve activity (RSNA) were examined, intravertebral administration of ANG II, while reducing the gain and the maximum RSNA, did not reset the RSNA baroreflex curve. These data suggest that ANG II acutely resets the HR baroreflex but not the RSNA baroreflex and that the resetting involves an alpha 1-adrenergic mechanism.
Role of hemodilution on renal responses to water immersion in humans
Authors: Johansen L. B. , Bie P. , Warberg J. , Christensen N. J. , Norsk P.
Published: December 2017

The present experiments were designed to elucidate 1) the role of the lower extremity capillary bed in decreasing plasma colloid osmotic pressure (COP) during immersion of humans (n = 8) for 6 h, and 2) the extent to which the natriuresis of water immersion is triggered by this decrease in COP. Irrespective of the depth, COPs were very similar during the immersion procedures, varying between 25.3 +/- 0.5 and 26.4 +/- 0.6 mmHg, which was significantly lower than during control (28.3 +/- 0.3 and 28.6 +/- 0.3 mmHg). During neck immersion, central venous pressure rose instantly by approximately 12 mmHg (P < 0.05) and remained elevated. Only a transient, marginal increase (1.6 +/- 0.7 mmHg) occurred during hip immersion. Cumulated sodium excretion during seated control, hip immersion, and neck immersion, respectively, differed significantly (30 +/- 5, 45 +/- 5, and 101 +/- 6 mmol). It is concluded that the decrease in COP during immersion is primarily due to fluid shifts occurring in the capillary bed of the legs and that this may account for up to 25% of the immersion-induced increase in renal sodium excretion.
Drinking after intragastric NaCl without increase in systemic plasma osmolality in rats
Authors: Kraly F. S. , Kim Y. M. , Dunham L. M. , Tribuzio R. A.
Published: December 2017

Drinking after intragastric hypertonic solutions was examined to determine whether increased plasma osmolality always accompanied initiation of drinking. A 2-ml infusion through a gastric catheter was the beginning of tests in Sprague-Dawley male rats. Latency to drink was shorter and 1-h water intake was greater for increasing concentrations of NaCl (600, 1,200, and 1,800 mosmol/kg) compared with baseline (290 mosmol/kg). Although 600, 900, or 1,200 mosmol/kg NaCl elicited drinking, such infusions failed to change systemic plasma osmolality, and 900 mosmol/kg also failed to change plasma sodium, protein, renin activity, or packed cell volume at the initiation of drinking. Intragastric 900 mosmol/kg sodium bicarbonate, sodium isethionate, potassium chloride, lithium chloride, and mannitol differentially increased water intake. Total subdiaphragmatic vagotomy abolished drinking elicited by intragastric NaCl; selective gastric or hepatic vagotomy attenuated intake under some conditions. These results support the hypothesis of a vagally mediated, gastrointestinal and/or hepatic-portal, osmosensitive mechanism for initiation of drinking in advance of postprandial increases in systemic osmolality.
No effect of aging on skeletal muscle insulin-like growth factor mRNAs
Authors: Hamilton M. T. , Marsh D. R. , Criswell D. S. , Lou W. , Booth F. W.
Published: December 2017

This study examined the hypothesis that during aging insulin-like growth factor (IGF) mRNAs are reduced in skeletal muscle. IGF-I, IGF-II, and IGF-binding protein-5 (IGFBP-5) mRNAs were measured with a ribonuclease protection assay in the gastrocnemius of specific pathogen-free Fischer-344 rats. We hypothesized that IGF-I, IGF-II, and IGFBP-5 mRNA concentration (normalized to 18S RNA) in the gastrocnemius muscle of growing animals (3 mo) would be downregulated in a coordinated manner with muscle size during aging-associated atrophy. As indicated by muscle wet weight and total protein content, the gastrocnemius muscle was growing in the 3-mo group (P < 0.01 smaller compared with 12 mo), fully developed at 12 mo, and was atrophied at 24 mo of age (P < 0.05 compared with 12 mo). IGF-I mRNA concentration in the gastrocnemius of 12- and 24-mo-old rats was 39-49% less than in 3-mo-old rats (P < 0.05). Contrary to our hypothesis, there was not a significant skeletal muscle IGF-I mRNA difference between middle age (12 mo) and senescence (24 mo). Thus IGF-I mRNA changed during maturation (3-12 mo) but not during aging (12-24 mo). Skeletal muscle IGF-II mRNA concentration was not different among 3-, 12-, and 24-mo-old animals. Furthermore, animal age did not have an effect on IGFBP-5 mRNA concentration. We conclude that the aging-associated atrophy of skeletal muscle is not caused by altered pretranslational regulation of IGF-I, IGF-II, or IGFBP-5 in skeletal muscle.
Botulinum-induced muscle paralysis alters metabolic gene expression and fatigue recovery
Authors: Gorin F. , Herrick K. , Froman B. , Palmer W. , Tait R. , Carlsen R.
Published: December 2017

We evaluated the physiological, histochemical, and biochemical consequences of inhibiting contractile activity in rat skeletal muscles with botulinum toxin A (BTX). Contractile activity was entirely eliminated 12-18 h after a single, focal, intramuscular injection of BTX into the rat tibialis anterior muscle (TA). Neuromuscular transmission remained completely inhibited for 10-12 days, then slowly recovered. BTX-treated muscles exhibited a lower resistance to both high- and low-frequency fatigue at 7 and 14 days after injection, but contractile force recovered more rapidly in treated TA after fatigue. Treated TA showed a twofold increase in the activity of the triglyceride hydrolase enzyme lipoprotein lipase (LPL) and a comparable increase in the relative abundance of LPL steady-state mRNA. In contrast, there was a 28% reduction in protein levels of the muscle isozyme of glycogen phosphorylase (MGP) and a 70% decrease in relative MGP transcript levels. Similar changes in relative transcript levels of LPL and MGP were observed in the predominantly fast-twitch extensor digitorum longus after BTX injection, but relative LPL and MGP mRNA levels were not altered in predominantly slow-twitch soleus. Histochemical evidence indicated that fast-twitch glycolytic fibers had increased lipid content. These biochemical alterations were reversed 120 days after BTX treatment despite persistent atrophy.
A prejunctional mechanism in midbrain periaqueductal gray inhibition of vagal bradycardia in rats
Authors: Nosaka S. , Inui K. , Murase S. , Murata K.
Published: December 2017

Stimulation of the dorsal part of the midbrain periaqueductal gray matter (dPAG) inhibits baroreflex vagal bradycardia (BVB) via a central mechanism. Here we report that the dPAG suppresses vagal bradycardia also by a peripheral mechanism. In chloralose-urethan-anesthetized, beta-blocked rats, the cervical vagus nerve was cut and the distal cut end was electrically stimulated to induce vagal bradycardia (VIB). Sustained electrical stimulation of the dPAG attenuated VIB in a duration-dependent manner but did not affect bradycardia induced by intravenous acetyl-choline (AIB). The dPAG inhibition of VIB was abolished by C1 transection. Intravenous norepinephrine (NE) reduced VIB but did not affect AIB. Both the dPAG and NE inhibitions of VIB were largely attenuated during intravenous prazosin, a selective alpha 1-receptor antagonist. In contrast, BVB provoked by aortic depressor nerve stimulation was remarkably inhibited by a shortly preceding dPAG stimulation, but this inhibition was not affected by C1 transection. Prazosin treatment did reduced the inhibition, but only moderately. In conclusion, the dPAG has a potential ability to suppress VIB by prejunctionally inhibiting acetylcholine release from cardiac vagus nerve terminals via alpha 1-receptors. However, dPAG stimulation first suppresses BVB largely at a central site, leaving a limited fraction of vagal outflow to be inhibited by a prejunctional mechanism operating with long latency.
Central trigeminal effects of somatostatin and etorphine on adrenal and autonomic function in the cat
Authors: Bereiter D. A. , Benetti A. P. , Bereiter D. F. , Hathaway C. B.
Published: December 2017

The influence of somatostatin and the potent mu-opiate receptor agonist etorphine on adrenal and autonomic responses mediated by trigeminal neurons was examined in chloralose-anesthetized cats. Microinjections of somatostatin (100 pmol) into laminae I-II of trigeminal subnucleus caudalis (Vc) evoked increases in the adrenal secretion of catecholamines and adrenal blood flow without affecting arterial pressure, heart rate, or plasma adrenocorticotropic hormone. Injections of somatostatin into laminae III-IV of Vc had no effect. Microinjections of etorphine (500 pmol) into laminae I-II of Vc had no effect, whereas injections into laminae III-IV caused small increases in total adrenal blood flow and peripheral concentrations of norepinephrine. To assess local effects of these drugs on peripheral trigeminal nociceptor-evoked autonomic responses, corneal stimulation was presented before and after topical application of somatostatin or etorphine on the dorsal brain stem surface. Somatostatin did not affect the adrenal and autonomic responses evoked by noxious thermal or chemical irritant stimulation of the cornea. Topical etorphine blocked completely the increase in adrenal blood flow, arterial pressure, and heart rate after noxious thermal stimulation of the cornea. These results suggest that somatostatin and mu-opiate receptor agonists act by different mechanisms at the level of the spinal trigeminal complex to affect adrenal and autonomic function.
Influence of circulating angiotensin II and vasopressin on neurons of the nucleus of the solitary tract
Authors: Hegarty A. A. , Hayward L. F. , Felder R. B.
Published: December 2017

The central cardiovascular effects of the circulating peptides angiotensin II (ANG II) and arginine vasopressin (AVP) may be mediated through the nucleus of the solitary tract (NTS). In this study, we used single-unit extracellular recording techniques to determine the effects of peripheral infusions of ANG II and AVP on NTS neurons. Barosensitive NTS neurons were characterized by their response to an increase in arterial pressure induced with phenylephrine (PE). Of 74 NTS neurons, 17 were excited by ANG II infusion. Of these, nine were also excited by activation of baroreceptors. ANG II inhibited 15 of 74 neurons, 13 of which were also baroinhibited. Of 77 NTS neurons, 13 were excited by AVP infusion, 7 of which were also baroexcited. One AVP-excited neuron was inhibited by a PE-induced increase in arterial pressure. Of 77 neurons, 21 were inhibited by AVP, 10 of which were also baroinhibited. Out of 21 AVP-inhibited neurons, 2 were excited by an increase in arterial pressure. These results indicate that some barosensitive NTS neurons may be independently influenced by circulating peptides and that separate populations of barosensitive and peptide-sensitive neurons are found in the NTS.
Consequences of weight cycling in obese spontaneously hypertensive rats
Authors: Ernsberger P. , Koletsky R. J. , Baskin J. S. , Collins L. A.
Published: December 2017

We mimicked human weight cycling in the obese spontaneously hypertensive rat (SHROB) model of genetic obesity. A 12-day very low calorie diet (VLCD; 16.7% of baseline calories) was alternated with 4-6 wk of ad libitum chow refeeding for three cycles. Control SHROB ate chow ad libitum. VLCD induced rapid weight loss, but during refeeding all the lost weight was regained. Final body weight was higher in cycled rats than in ad libitum controls (149 +/- 5 vs. 117 +/- 7% of initial baseline). Less weight was lost as a percent of starting body weight during each successive VLCD, which could not be explained by aging. At death, retroperitoneal fat pads were heavier in cycled SHROB than in ad libitum controls (62 +/- 3 vs. 44 +/- 4 g). During the first 2 days after each VLCD, cycled rats overate significantly relative to ad libitum controls (88 +/- 2 vs. 78 +/- 3 kcal/day), but cumulative food intake throughout the duration of the experiment did not differ (11.4 +/- 0.6 vs. 11.7 +/- 0.1 Mcal). Compared with ad libitum-fed rats, food efficiency (g body wt gain/kcal) was increased during each refeeding period. Weight cycling elevated blood pressure above the initial baseline throughout refeeding. Refeeding hypertension was abolished by ganglionic blockade with chlorisondamine. Thus weight cycling in SHROB exacerbates obesity, metabolic efficiency, abdominal fat accumulation, sympathetic activity, and hypertension.
Involvement of transcription factor C/EBP-beta in stimulation of PEPCK gene expression during exercise
Authors: Nizielski S. E. , Arizmendi C. , Shteyngarts A. R. , Farrell C. J. , Friedman J. E.
Published: December 2017

Prolonged exercise increases gluconeogenesis and activates transcription of the hepatic phosphoenol pyruvate carboxykinase (PEPCK) gene. The mechanisms that regulate the transcriptional control of gene expression depend on the interaction of nuclear proteins with distinct DNA sequences. To determine the involvement with the liver-enriched transcription factor CCAAT/enhancer binding protein beta (C/EMP-beta) in the induction of PEPCK gene transcription during prolonged exercise or adenosine 3',5'-cyclic monophosphate (cAMP) treatment, we examined C/EBP-beta mRNA and nuclear protein concentrations, as well as C/EBP-beta binding to the PEPCK promoter at the cAMP response element (CRE)(-87/-74) and P3I (-248/-230) binding sites. The requirement of these DNA elements for exercise-induced stimulation of PEPCK gene expression was established in transgenic mice carrying -460 +/- 73 of the PEPCK promoter with a mutation in either the CRE or P3I binding domain linked to a bovine growth hormone (bGH) reporter gene. In mice carrying the intact promoter, prolonged exercise increased the concentration of liver bGH mRNA by 510% compared with an increase of only 270% in mice with a mutation in either the CRE or P3I site. Exercise or cAMP injection induced a 7.5- and 13-fold increase in nuclear C/EBP-beta protein, respectively. In electrophoretic mobility shift assays (EMSA), the total quantity of nuclear proteins bound to either oligomer was not altered by treatment. However, addition of C/EBP-beta antisera in the EMSA in a supershift assay indicated that liver nuclear extracts from exercised or cAMP-treated mice demonstrated significantly greater DNA binding due to C/EBP-beta (CRE: control 44.4 +/- 2.3%, exercise 56.7% +/- 2.2%, cAMP 54.5 +/- 3.6% of total binding, P < 0.001; P3I: control 35.8 +/- 2.5%, exercise 64.9 +/- 1.9%, cAMP 57.3 +/- 2.5% of total binding, P < 0.001). Taken together, these results suggest that exercise and cAMP treatment induce a transient increase in C/EBP-beta that may contribute to the molecular mechanism for signaling PEPCK gene transcription and increasing gluconeogenesis during exercise.
Role of paraventricular angiotensin AT1 receptors in salt-sensitive hypertension in mRen-2 transgenic rats
Authors: Li P. , Morris M. , Diz D. I. , Ferrario C. M. , Ganten D. , Callahan M. F.
Published: December 2017

We have previously demonstrated that mRen-2 transgenic [Tg(+)] rats show a salt-induced exacerbation of hypertension (Callaha, M., P. Li, C. M. Ferrario, D. Ganten, and M. Morris. Hypertension Dallas 27: 573-577, 1996). In this study, we examined the role of paraventricular (PVN) angiotensin type-1 (AT1) receptors in the salt sensitivity of this model. Male Tg(+) and Tg(-) rats were instrumented with PVN cannulas for intracerebral drug administration and carotid catheters for chronic cardiovascular monitoring. Substitution of 2% NaCl for drinking water for 4 days caused a significant elevation (23 mmHg) of mean arterial pressure (MAP) in Tg(+) rats but not in Tg(-) rats. PVN injection of AT1 receptor antisense oligodeoxynucleotides (ASODN), but not scrambled oligodeoxynucleotides (SCODN), produced a rapid decrease in MAP of 24 +/_ 8 mmHg in salt-treated Tg(+) rats. There was no effect of either AT1 ASODN or SCODN on MAP in salt-loaded Tg(-) rats or in Tg(+) rats consuming tap water. Salt loading significantly increased subfornical organ AT1 receptors in Tg(+) rats with no changes produced by ASODN or SCODN. In contrast, there was a 40% decrease in PVN AT1 receptors 20 h after direct PVN injection of AT1 ASODN injection, compared with SCODN in Tg(+) rats. We conclude that PVN AT1 receptors are critical in the expression of salt sensitivity in mRen-2 transgenic rats.
Application of acute maximal exercise to protect orthostatic tolerance after simulated microgravity
Authors: Engelke K. A. , Doerr D. F. , Convertino V. A.
Published: December 2017

Pages R837–R847: K. A. Engelke, D. F. Doerr, and V. A. Convertino. “Application of acute maximal exercise to protect orthostatic tolerance after simulated microgravity.” On p. 837, the author line of the article and abstract and the affiliation line should read as follows:

KEITH A. ENGELKE, DONALD F. DOERR,CRAIG G. CRANDALL, AND VICTOR A. CONVERTINO

Department of Physiology, University of Florida, Gainesville, Florida 32610; National Aeronautics and Space Administration-Kennedy Space Center, Cape Canaveral, Florida 32899;Department of Physiology, University of North Texas Health Science Center, Ft. Worth, Texas 76107; and Physiology Research Branch, Clinical Science Division, Brooks Air Force Base, Texas 78235
Identification and characterization of zeta-opioid receptor in human colon cancer
Authors: Hytrek S. D. , Smith J. P. , McGarrity T. J. , McLaughlin P. J. , Lang C. M. , Zagon I. S.
Published: December 2017

Opioid growth factor (OGF, [Met5]enkephalin) inhibits the growth of human colon cancer in nude mice in a receptor-mediated fashion. Ligand binding assays using HT-29 human colon cancer tissue and [3H][Met5]enkephalin were performed to characterize the receptor responsible for the growth-regulatory effects of OGF in colon cancer. Specific and saturable binding was detected, and Scatchard analysis revealed that the data were consistent for a single binding site with a binding affinity of 15.4 +/- 2.0 nM and a binding capacity of 364.8 +/- 25.7 fmol/mg protein. Subcellular fractionation studies revealed that binding was restricted to the nuclear fraction. Competition experiments showed that cold [Met5]enkephalin was the most effective ligand at displacing [3H][Met5]enkephalin. Binding to radiolabeled [Met5]enkephalin also was detected in colon cancers obtained from surgical resections. The function, pharmacological and biochemical characteristics, distribution, and subcellular location of this OGF receptor in human colon cancer are consistent with the zeta-opioid receptor.
Lymphocytes and NK cell activity during repeated bouts of maximal exercise
Authors: Nielsen H. B. , Secher N. H. , Christensen N. J. , Pedersen B. K.
Published: December 2017

Effects on the immune system of 6-min “all-out” ergometer rowing were investigated over 2 days (2 x 3 bouts) in eight male oarsmen with a maximal oxygen uptake of 5.5 +/- 0.1 l/min (mean +/- SE). Blood samples were obtained before, during, and 2 h after each bout and on the day after the last bout. Compared with levels at rest, the first bout of exercise increased the concentration of leukocytes (2-fold); neutrophilic granulocytes (2-fold); lymphocytes (2-fold); monocytes (2-fold); the blood mononuclear cell (BMNC) subsets CD3+ (2-fold), CD4+ (2-fold), CD8+ (3-fold), CD16+ (8-fold), CD19+ (2-fold), and CD14+ (2-fold); the NK cell activity (2-fold); and plasma interleukin-6 (3-fold) (P < 0.05). During the last bout even higher levels were noted for leukocytes (3-fold); neutrophilic granulocytes (3-fold); lymphocytes (4-fold); the BMNC subsets CD4+ (3-fold), CD8+ (5-fold), CD16+ (13-fold), CD19+ (5-fold), and CD14+ (3-fold); and for the NK cell activity (4-fold) (P < 0.05). During the recovery periods all values were at or above the level at rest, and elevated concentrations of leukocytes (38%), neutrophilic granulocytes (48%), and lymphocytes (46%) reflected in the BMNC subsets and increased NK cell activity (119%) were also noted on the day after the last bout (P < 0.05). The results show that maximal exercise with large muscle groups provokes higher immune responses during repetitive bouts.
Autoregulation of myocardial glycogen concentration during intermittent hypoxia
Authors: McNulty P. H. , Ng C. , Liu W. X. , Jagasia D. , Letsou G. V. , Baldwin J. C. , Soufer R.
Published: December 2017

During hypoxia, the heart consumes glycogen to generate ATP. Tolerance of repetitive hypoxia logically requires prompt replenishment of glycogen, a process whose regulation is not fully understood. To examine this, we imposed a defined hypoxic stimulus on the rat heart while varying its workload. In intact rats, hypoxia reduced myocardial glycogen approximately 30% and increased both the fraction of glycogen synthase in its physiologically active (GS I) form (from 0.24 +/- 0.06 to 0.82 +/- 0.07; P < 0.005) and glycogen synthesis (from 0.087 +/- 0.011 to 0.375 +/- 0.046 mumol.g-1.min-1; P < 0.005). Reducing cardiac work (with propranolol or heterotopic transplantation) reduced glycogen breakdown, glycogen synthase activation, and glycogen synthesis in parallel, stepwise fashion in intact rats. Correspondingly, hypoxia increased GS I activity in the perfused heart in vitro, but only under conditions where glycogen was consumed. This suggests myocardial glycogen synthase is activated by systemic hypoxia and catalyzes rapid posthypoxic glycogen synthesis. Hypoxic glycogen synthase activation appears to be a proportionate, wholly intrinsic response to local glycogenolysis, operating to preserve myocardial glycogen stores independent of any extracardiac mediator of carbohydrate metabolism.
Bradykinin B2 receptor antagonist increases chloride and water absorption in rat medullary collecting duct
Authors: Mukai H. , Fitzgibbon W. R. , Bozeman G. , Margolius H. S. , Ploth D. W.
Published: December 2017

This study tested the hypothesis that intrarenal kinins play a regulatory role in electrolyte excretion by altering Cl- absorption in the collecting duct. We measured Cl- and insulin concentrations in tubular fluid samples obtained from medullary collecting ducts (MCD) of Dahl/Rapp salt-resistant (SR/ Jr) rats by microcatheterization of ducts of Bellini before and after treatment with the bradykinin receptor antagonist HOE-140. Tubular fluid was obtained from paired terminal inner medullary (t-IMCD) and outer medullary (OMCD) collecting duct sites of the left kidney. HOE-140 (n = 7) or vehicle (n = 5) was infused intravenously, and the collections were repeated. HOE-140 did not alter glomerular filtration rate but decreased urine flow rate (P < 0.05) and absolute and fractional Cl- excretion (P < 0.01). HOE-140 did not alter the fraction of filtered Cl- delivered (FDCl) to the OMCD but decreased FDCl to the t-IMCD from 2.3 +/- 0.3 to 1.3 +/- 0.3% (P < 0.05). The fraction of filtered Cl- absorbed per millimeter between the collection sites was increased from 0.2 +/- 0.1 to 0.6 +/- 0.1% (P < 0.05). Fractional absorption of water along the MCD was also increased (P < 0.05). No changes in excretory function or tubular Cl- or water absorption were observed in vehicle-treated rats. These studies show that kinin B2 receptor blockade enhances Cl- and water absorption in the MCD, a finding that supports a role of renal kinins in the regulation of NaCl and water excretion.