bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of corticosteroid receptors in gills of coho salmon due to stress and cortisol treatment
Authors: Shrimpton J. M. , Randall D. J.
Published: December 2017

The effect of stress and cortisol treatment on corticosteroid receptors (CRs) in the gills of coho salmon (Oncorhynchus kisutch) was examined. Plasma cortisol levels were elevated acutely by intraperitoneal injection of cortisol 21-hemisuccinate and chronically by implanting miniosmotic pumps filled with cortisol or by repeated daily handling stresses. CR concentration and affinity were measured by radioreceptor assay employing 3H-labeled triamcinolone acetonide as ligand. Acute administration of cortisol resulted in a reduction in CR numbers for 72 h with no change in affinity. Chronic cortisol treatment resulted in a decrease in CR concentration and affinity. The change in affinity occurred only while plasma cortisol levels remained elevated, but CR population remained significantly reduced for at least 10 days after cessation of hormone treatment. Repeated handling stresses resulted in a similar reduction in CR numbers but without an apparent change in affinity. The chronic or repeated elevation in plasma cortisol downregulates the sensitivity of the gills to cortisol by a persistent reduction in CR concentration, despite the return to nonstress levels of circulating cortisol.
TNF-alpha and IL-6 expression in perfused rat liver after intraportal candidemia vs. E. coli or S. aureus bacteremia
Authors: Matuschak G. M. , Munoz C. , Epperly N. A. , Britton R. S. , Walsh D. , Schilly D. R. , Tredway T. L. , Khan T. A. , Bacon B. R. , Lechner A. J.
Published: December 2017

We tested the hypothesis that regulation of tumor necrosis factor-alpha (TNF-alpha) and IL-6 by the liver differs after intraportal challenge with Candida albicans spp. vs. gram-negative or gram-positive bacteria, independent of microbial clearance kinetics or hepatic O2 consumption (VO2). Buffer-perfused rat livers were infected with equivalent inocula (10(9) colony-forming units) of viable Escherichia coli serotype 055:B5 (EC), exotoxin C-producing Staphylococcus aureus (SA), or two strains of yeast phase C. albicans (CA-1 and CA-2). Microbial clearance and circulating cytokine levels were assessed over 180 min while monitoring VO2 and functional parameters, after which organ-based microbial killing, cell-associated TNF-alpha, and cytokine mRNA levels were determined. Compared with saline controls (normal saline solution; NSS), circulating and cell-associated TNF-alpha and TNF-alpha transcripts minimally increased after CA. In contrast, large increases in perfusate TNF-alpha occurred after EC, peaking at 180 min [135 +/- 32 U/ml (mean + SE)], concomitant with rises in cell-associated cytokine and TNF-alpha transcripts (P < 0.01 vs. NSS). Circulating TNF-alpha also rose after SA but neither cell-associated nor mRNA levels exceeded NSS values. There were no pathogen-specific differences in microbial clearance or VO2. IL-6 gene expression paralleled that for TNF-alpha, but IL-6 bioactivity in perfusates was inhibited by TNF-alpha-dependent and -independent mechanisms. We conclude that hepatic TNF-alpha and IL-6 expression are differentially regulated after taxonomically diverse microbial challenges, with E. coli eliciting the strongest and Candida spp. the weakest stimulatory responses.
Plasma-derived serum from hypertensive rats differentially increases growth of cultured arteriolar smooth muscle
Authors: Overbeck H. W. , Dubey R. K.
Published: December 2017

A role for humoral factors in the arterial hypertrophy accompanying hypertension has been suggested, but direct evidence is lacking. We measured [3H]thymidine incorporation of growth-arrested smooth muscle cells, cultured from renal preglomerular arterioles of normal rats and exposed for 12 h to 10% platelet-poor plasma-derived serum (PDS) from male rats with early, benign, one-kidney, one-clip hypertension and paired one-kidney normotensive control rats. In the presence of low background concentrations (1-2%) of fetal calf serum, PDS from hypertensive rats increased [3H]thymidine incorporation up to 117% more than PDS from normotensive rats (P < 0.0001). Results were similar for the < 10,000 mol wt fraction of PDS and for PDS from rats drinking saline vs. water or eating a 7% (high) vs. a 0.45% NaCl diet. PDS from hypertensive rats also differentially increased smooth muscle cell proliferation and c-fos mRNA expression. Platelet-derived growth factor levels in PDS were undetectable (< 0.17 ng/ml). This study provides evidence for altered concentrations of sodium chloride-unresponsive plasma factor or factors in hypertension that result in enhanced growth of arteriolar smooth muscle cells.
Reduced glucose availability induces torpor in Siberian hamsters
Authors: Dark J. , Miller D. R. , Zucker I.
Published: December 2017

Siberian hamsters kept in long photoperiods (16 h light/day) at 10 degrees C do not display torpor when provided with food ad libitum but do reduce their body temperatures (Tb) from 37 degrees C to as low as 15 degrees C for several hours each day in response to food restriction. Female hamsters maintained in a long photoperiod and fed ad libitum were injected with 2-deoxy-D-glucose (2-DG), a glucose analogue that reduces cellular glucose oxidation, or mercaptoacetate (MA), a drug that disrupts fatty acid oxidation. Dosages of 2-DG in excess of 1,500 mg/kg body mass reliably induced torpor with latencies of approximately 50 min from time of injection to a decrease in Tb below 30 degrees C; 79% of females displayed torpor at a dosage of 2,500 mg/kg. MA was uniformly ineffective in inducing torpor and did not increase incidence of torpor when combined with 2-DG treatment or food restriction. Decreased availability of glucose may be the major metabolic signal for inducing torpor in Siberian hamsters; availability of fatty acids appears to play little if any role in regulating this behavior.
A5 noradrenergic neurons and the carotid sympathetic chemoreflex
Authors: Koshiya N. , Guyenet P. G.
Published: December 2017

Inhibition of neural activity in the caudal ventrolateral pons (A5 area) by microinjection of muscimol (Mus) attenuates (-65%) the carotid sympathetic chemoreflex (SChR) without altering the concomitant activation of the phrenic nerve (PND). The present study, performed in urethan-anesthetized rats, explores the possibility that activation of the noradrenergic (NE) neurons of the A5 area is involved in the SChR. The NE neuron-selective toxin 6-hydroxydopamine (6-OHDA) was microinjected bilaterally into the spinal cord at T2 level (4 micrograms). This dose reduced the SChR by 55% (n = 5) 90 min after injection, while 0.4 microgram of 6-OHDA produced no effect (n = 5). In seven rats that had received 250 micrograms 6-OHDA intracisternally 2 wk before, Mus injections into the A5 area failed to attenuate the SChR. These rats also had a lower resting mean arterial pressure than controls (97 vs. 112 mmHg). Spinal intrathecal injection of alpha-adrenergic receptor antagonists (prazosin, 10 and 20 micrograms) or phentolamine (20 and 40 micrograms) attenuated resting sympathetic nerve discharge (SND) and SChR in a roughly proportional manner (25-40%); the beta-adrenergic antagonist nadolol (10 and 20 microgram(s) intrathecally) attenuated the SChR selectively but modestly (-10%). The results are generally compatible with the hypothesis that A5 NE neurons and particularly their spinal cord projection could play a facilitating role in the SChR. However, clear evidence that A5 cells contribute selectively to sympathoactivation during chemoreceptor stimulation by releasing NE in the spinal cord could not be obtained.
Diet cycling and age alter weight gain and insulin levels in rats
Authors: Levin B. E.
Published: December 2017

For assessment of the effect of diet cycling on body weight gain patterns, 3-mo-old male Sprague-Dawley rats were either cycled from chow to a high-energy condensed milk (CM) diet, back to chow, and then back to CM diet at 3-mo intervals (cyclers) or were fed chow to 9 mo of age and then CM diet for 3 mo (noncyclers). Nine of 21 cyclers developed diet-induced obesity (DIO), gaining 36, 59, and 281% more weight than chow-fed controls (CF) at each cycle, respectively. Twelve cycled rats were diet-resistant (DR) with comparable weight gain to CF rats after the first CM diet and chow cycles. However, they gained 202% more than CF rats and 50% more, with 29% heavier retroperitoneal fat pads, than noncycled DR rats after their second CM diet cycle begun at 9 mo of age. Enhanced weight gain in DR cyclers was probably due to enhanced food efficiency in the last few weeks of CM diet intake. Plasma insulin levels were 70% higher in cycled vs. noncycled DIO and DR rats, and both were higher than CF rats. Unlike 6-mo-old DR rats in a prior study, 12-mo-old noncycled DR rats after 3 mo on CM diet here had 45-172% higher alpha 2-adrenoceptors binding in 6 of 17 brain areas than noncycled DIO and/or CF rats. Thus age, diet cycling, and brain alpha 2-adrenoceptors interact to affect long-term changes in weight gain and metabolism.
Altered renal P-450 metabolism of arachidonic acid in Dahl salt-sensitive rats
Authors: Ma Y. H. , Schwartzman M. L. , Roman R. J.
Published: December 2017

The renal metabolism of arachidonic acid (AA) was compared in male and female prehypertensive Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats maintained on a low- (0.3%) sodium chloride diet. Renal cortical microsomes incubated with AA produced 20-hydroxyeicosatetraenoic acid (20-HETE), 14,15- and 11,12-epoxyeicosatrienoic acids, and a new metabolite of AA, 11,12-epoxy-20-hydroxyeicosatrienoic acid. The production of 20-HETE was similar in cortical microsomes of female SS/Jr and SR/Jr rats maintained on a low-salt diet (72 +/- 5 vs. 66 +/- 3 pmol.min-1.mg protein-1); however, the formation of epoxygenase metabolites was significantly less in SS/Jr than in SR/Jr rats (45 +/- 2 vs. 70 +/- 3 pmol.min-1.mg protein-1). Outer medullary microsomes produced primarily 20-HETE, and the formation of this compound was significantly lower in SS/Jr than in SR/Jr female rats fed a low-salt diet (8 +/- 2 vs. 18 +/- 3 pmol.min-1.mg protein-1). Renal papillary microsomes produced prostaglandin E2 and F2 alpha, and the formation of these compounds was similar in female SS/Jr and SR/Jr rats fed a low-salt diet. Similar differences in the metabolism of AA by P-450 were observed in microsomes prepared from the renal cortex and outer medulla of male SS/Jr and SR/Jr rats. These results indicate that the renal metabolism of AA by P-450 is altered in prehypertensive Dahl SS/Jr rats; however, the functional significance of this system in resetting renal function and in the development of hypertension in this model remains to be established.
Phosphoinositide turnover signaling stimulated by ET-3 in endothelial cells from spontaneously hypertensive rats
Authors: Yokokawa K. , Johnson J. , Kohno M. , Mandal A. K. , Yanagisawa M. , Horio T. , Yasunari K. , Takeda T.
Published: December 2017

Endothelin (ET) B-type receptor-mediated signal transduction after stimulation with ET-3 was examined in cultured aortic endothelial cells obtained from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. The purpose of this study was to elucidate ETB receptor-mediated response in endothelial cells from hypertensive rat models. Non-isopeptide-selective displacement and affinity in these binding experiments suggest that aortic endothelial cell receptors for ET-3 correspond to ETB receptor subtypes. These receptors for ET-3 were similar in WKY and SHR endothelial cells. ETB receptor mRNA expression in cultured endothelial cells was also similar in WKY and SHR. However, the cytosolic free Ca2+ level in the absence of extracellular Ca2+ as well as the inositol 1,4,5-trisphosphate level in response to ET-3 were greater in endothelial cells from SHR than in those from WKY. Phospholipase C and protein kinase C activities after stimulation with ET-3 were also greater in SHR than in WKY. The 6-ketoprostaglandin F1 alpha production was also augmented in SHR, although nitric oxide formation and guanosine 3',5'-cyclic monophosphate production after stimulation with ET-3 were similar in WKY and SHR. We conclude that the phosphoinositide turnover signaling stimulated by ET-3 is augmented in cultured aortic endothelial cells from SHR compared with those from WKY.
Central and systemic kappa-opioid agonists exacerbate neurobehavioral response to brain injury in rats
Authors: McIntosh T. K. , Fernyak S. , Yamakami I. , Faden A. I.
Published: December 2017

The endogenous opioid peptide dynorphin has been implicated in the pathophysiology of secondary tissue injury after central nervous system (CNS) trauma. The detrimental effects of dynorphin appear to be mediated through both opioid receptors (probably kappa-receptors) and nonopioid mechanisms. However, both kappa-opioid agonists and antagonists have been reported to improve outcome in models of CNS trauma. To attempt to clarify this controversy, we examined the effects of centrally or systemically administered kappa-opioid agonists on neurological recovery after experimental fluid-percussion brain injury in the rat. Agonists included dynorphin A-(1-17) [Dyn A-(1-17)], which has actions at both kappa 1- and kappa 2-sites, and the selective kappa 1-agonists U-50,488H and U-69,593. des-Tyr-dynorphin A-(2-17) [Dyn A-(2-17)], which is inactive at opioid receptors, was also used. Microinjection of Dyn A-(1-17), but not Dyn A-(2-17) or U-50,488H, into the lateral ventricle 15 min before brain injury significantly worsened motor deficits over a 2-wk period. However, systemic administration of high doses of the kappa-agonists U-50,488H and U-69,593 also significantly worsened neurological outcome. These results fail to demonstrate any protective actions of kappa 1-agonists in this model of experimental traumatic brain injury and suggest that the opioid-related pathophysiological actions of dynorphin may be mediated by kappa 2-opioid receptors.
Nonuniform enhancement of baroreflex sensitivity by atrial natriuretic peptide in conscious rats and dogs
Authors: Woods R. L. , Courneya C. A. , Head G. A.
Published: December 2017

The influence of atrial natriuretic peptide (ANP) on the blood pressure (BP)-heart rate (HR) baroreflex was studied in conscious chronically instrumented dogs and rats. In both species, sigmoid steady-state baroreflex curves were constructed from the baroreflex changes in HR to alternating slow injections of vasopressor and vasodepressor drugs. When this method was used in dogs, ANP caused a small but significant (P < 0.05) enhancement of the sensitivity (22 +/- 10%) and curvature (26 +/- 10%) of the baroreflex, which was without a change in HR range. In rats, ANP had no significant effect on any baroreflex parameter derived from steady-state curves. By contrast, in the same rats, fast reflex HR responses to rapid increases in BP (ramp) exposed a substantial (81 +/- 21%) ANP-induced enhancement of baroreflex sensitivity. Contribution from arterial vs. nonarterial afferents to the baroreflex is not uniform between these two techniques (steady state reflects largely arterial baroreceptor input, ramp evokes a greater proportion of cardiopulmonary afferent activation). The present study demonstrated that baroreceptor HR reflex responses to ANP depend on the baroreflex techniques employed and probably exposed a selectivity by ANP for nonarterial baroreflex pathways.
Effect of chronic ANG I-converting enzyme inhibition on aging processes. IV. Cerebral blood flow regulation
Authors: Lartaud I. , Makki T. , Bray-des-Boscs L. , Niederhoffer N. , Atkinson J. , Corman B. , Capdeville-Atkinson C.
Published: December 2017

Age-related changes in systemic arterial blood pressure, basal cerebral blood flow (CBF), and CBF regulatory capacity were investigated in awake 6-, 12-, 24-, and 30-mo-old male Wistar (WAG/Rij) rats, one-half of which received the angiotensin I-converting enzyme inhibitor (ACEI) perindopril from 6 mo onward. There was no age-dependent change in mean arterial blood pressure, basal CBF, or cerebrovascular reactivity to hypercapnia, but the lower limit of CBF autoregulation rose from 70 mmHg at 6 and 12 mo to 90 mmHg in 24- and 30-mo-old animals. ACEI lowered mean arterial blood pressure but had no effect on basal CBF or on cerebrovascular reactivity to hypercapnia. ACEI shifted the lower limit of CBF autoregulation to a 20-mmHg-lower level in 12- and 24-mo animals but not in rats treated for 2 yr, i.e., from the ages of 6 to 30 mo. In conclusion, the main age-related change in CBF regulation was an increase in the lower limit of CBF autoregulation to a higher blood pressure level. Treatment with ACEI partially restored the lower limit of CBF autoregulation.
Effect of chronic blood pressure reduction on soleus muscle contractile properties in spontaneously hypertensive rats
Authors: Gray S. D. , Carlsen R. C. , Atherley R.
Published: December 2017

Soleus muscle in Wistar-Kyoto rats (WKY), as well as in most normotensive mammals, is highly fatigue resistant. In 6-mo-old spontaneously hypertensive rats (SHR), however, soleus muscle generates less specific force and experiences a more rapid rate of fatigue than in age-matched WKY. The present experiments tested the hypothesis that antihypertensive treatment with hydralazine or amlodipine would shift the contractile force and fatigue resistance profile of SHR soleus toward that which characterizes WKY. Hydralazine was given via the drinking water (100 mg/l) and amlodipine via the food (1 g/4 kg rat chow) to two separate groups of animals, starting at the age of 16 wk. At 24-26 wk of age soleus twitch and tetanic force generation and the rate of fatigue were evaluated during a 4-min period of repetitive stimulation. Although both hydralazine and amlodipine lowered blood pressure, they had different effects on muscle function. Hydralazine decreased force generation in both WKY and SHR at all stimulation frequencies; it did not change the fatigue properties of SHR but made WKY soleus less fatigue resistant. Amlodipine, on the other hand, increased contractile force in both WKY and SHR and increased fatigue resistance in SHR. Amlodipine is a dihydropyridine that blocks L-type channels, thereby preventing entry of Ca2+ into the muscle. We suggest that Ca2+ entry during activity stimulates Ca-activated K+ efflux in SHR and adds to the extracellular load of K+. Increased extracellular K+ can in turn depress contractile performance.
Parasympathetic-mediated reflex salivation and vasodilatation in the cat submandibular gland
Authors: Izumi H. , Karita K.
Published: December 2017

The aim of the present study was to compare and characterize the secretory and vasodilator effects induced by chorda lingual nerve (CLN) stimulation (i.e., direct parasympathetic stimulation) and reflex parasympathetic stimulation in the submandibular gland (SMG) of sympathectomized cats. The increase in blood flow and salivary secretion in response to electrical stimulation of the central cut ends of the vagus and inferior alveolar nerves, as well as to stimulation of the CLN at a site approximately 5 mm distal to the intersection of the CLN and the SMG duct (site D) was completely abolished by section of the chorda tympani nerve (CTN). Neither response to CLN stimulation at a site nearly 5 mm proximal to the intersection of the CLN and the SMG duct (site C) was affected by CTN section. Section of the CLN at a site approximately 5 mm distal to the intersection of the CTN and the CLN abolished the submandibular salivary and vasodilator responses elicited by CLN stimulation at site D but had no effect on the two responses evoked by CLN stimulation at site C. The blood flow increases evoked by electrical stimulation of the CLN at site D were greatly reduced by prior treatment with the autonomic ganglion blocker hexamethonium, but the vasodilator responses evoked from site C were reduced much less. These data suggest that the secretory and vasodilator responses elicited by CLN stimulation at site D and those by vagus and inferior alveolar nerve stimulation are mediated largely via a parasympathetic reflex mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential regulation of central vasopressin in transgenic rats harboring the mouse Ren-2 gene
Authors: Moriguchi A. , Ferrario C. M. , Brosnihan K. B. , Ganten D. , Morris M.
Published: December 2017

The transgenic (TG) rat carrying the mouse renin gene (mRen-2d) has provided a unique opportunity to explore central interactions between the brain renin-angiotensin (RAS) and vasopressin (AVP) systems. To evaluate the hypothalamic vasopressin axis in the TG rat, we measured the central nervous system concentrations of AVP and determined the effect of angiotensin II (ANG II) and its NH2-terminal heptapeptide [angiotensin-(1-7)] on blood pressure, heart rate, and AVP release using brain microdialysis. Intracerebroventricular infusion of ANG II or ANG-(1-7) in control rats increased local AVP release from the paraventricular and supraoptic nuclei. The ANG II infusion was associated with a significant increase in blood pressure not observed with ANG-(1-7). In contrast, the angiotensin peptide-induced central AVP responses and the ANG II-induced blood pressure increase were absent in the TG animal. The plasma AVP responses to ANG II and ANG-(1-7) were comparable in the control and TG rats. The TG rats exhibited a 22-fold higher level of AVP in the dorsal lower brain stem but had lower AVP levels in the posterior pituitary and the median eminence compared with control rats. These results suggest that insertion of the mouse renin gene into the rat genome leads to alterations in the AVP axis in terms of AVP peptide content and angiotensin-induced cardiovascular and AVP responses.
Cardiovascular activation by serotonergic stimulation: role of corticotropin-releasing factor
Authors: Dedeoglu A. , Fisher L. A.
Published: December 2017

Serotonin (5-HT) and serotonergic agonists stimulate the release of corticotropin-releasing factor (CRF) from hypophysiotropic neurons and thereby activate the pituitary-adrenal axis. Studies were performed to test the hypothesis that the release of CRF into central nervous system (CNS) sites where it influences cardiovascular function is likewise stimulated by serotonergic mechanisms. Experiments were thus designed to examine whether the cardiovascular effects of central administration of low doses of 5-HT and the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), are secondary to the release of CRF. Intracerebroventricular administration of 5-HT (1 nmol) and 8-OH-DPAT (3 nmol) produced cardiovascular responses similar to those evoked by CRF (0.15 nmol), i.e., simultaneous elevations of arterial pressure and heart rate, in conscious unrestrained rats. Coadministration of the CRF receptor antagonist, alpha-helical CRF-(9-41) (9 nmol), significantly attenuated the pressor and tachycardic responses to 5-HT and 8-OH-DPAT as well as those to injection of CRF. In contrast, coadministration of alpha-helical CRF-(9-41) did not alter the pressor and bradycardic responses to a high dose (100 nmol) of serotonin. It is concluded that the cardiovascular effects of low doses of 5-HT and 8-OH-DPAT are mediated in part through the release of CRF within the CNS.
Basis for differential coupling between rhythmic discharges of sympathetic efferent nerves
Authors: Kocsis B.
Published: December 2017

The relationships between activities of three sympathetic efferents [vertebral (VN); cardiac (CN); and renal nerves (RN)] of 45 chloralose-urethan anesthetized cats were investigated using multivariate spectral analysis. The multiple coherences measuring the extent to which one nerve signal may be predicted from the other two were very high (0.77-0.83) at the peak frequency of synchronized rhythmic activity, indicating that specific components comprised < 20% of the power in the nerve signals. The pattern of sympathetic activity was characterized by the partial coherences calculated for different nerve pairs after the components common for all three nerve signals were removed. In baroreceptor-intact cats, partialization on the CN signal drastically reduced the coherences between the VN and RN (0.25), whereas the coherences between the CN activity and either of the vasoconstrictors remained high after partialization on the other vasoconstrictor (0.52 and 0.43). In baroreceptor-denervated cats, partial coherence was high between vertebral and cardiac nerves (0.52) and low between renal and any other nerve discharge (0.19-0.20). In individual experiments, five different patterns of coupling were observed, and their separation was tested by cluster analysis.
Both NMDA and non-NMDA receptors in the NTS participate in the baroreceptor reflex in rats
Authors: Ohta H. , Talman W. T.
Published: December 2017

In this study, we determined whether either N-methyl-D-aspartate (NMDA) receptors or non-NMDA receptors in the nucleus tractus solitarii (NTS) participate in the baroreceptor reflex in rats. Microinjection of an NMDA receptor antagonist, MK-801, and a non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, into the NTS decreased the sensitivity of the baroreceptor reflex by 51 and 41%, respectively. Simultaneous administration of both agents further reduced the sensitivity of the baroreceptor reflex to 28% of control. A competitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid, also attenuated reflex bradycardia or tachycardia elicited by a single dose of phenylephrine or nitroprusside, respectively. Specificity of each antagonist's effects was supported by selective blockade of depressor responses produced by agonists that act at the NMDA and non-NMDA receptors, respectively. Results of this study indicate that both non-NMDA- and NMDA-sensitive receptors are involved in baroreceptor reflex transmission in the NTS.
Na(+)-K(+)-ATPase inhibition sensitizes renal mechanoreceptors activated by increases in renal pelvic pressure
Authors: Kopp U. C. , Smith L. A. , Pence A. L.
Published: December 2017

In anesthetized rats, the activation threshold of renal pelvic mechanoreceptors was determined by graded increases in renal pelvic pressure. Ipsilateral afferent renal nerve activity increased 9 +/- 4 (NS), 34 +/- 12, 47 +/- 8, 58 +/- 13, 68 +/- 14, and 91 +/- 17% (all P < 0.01) by the increase in renal pelvic pressure from 2.5 to 15 mmHg in 2.5-mmHg steps. Contralateral diuresis and natriuresis were elicited by renal pelvic pressures > 2.5 mmHg. Renal pelvic perfusion with 1.4 mM ouabain, an inhibitor of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase), increased basal afferent renal nerve activity transiently, lowered the activation threshold of renal mechanoreceptors to < 2.5 mmHg, and enhanced the afferent renal nerve activity, responses to increasing renal pelvic pressures by 8 and 30 mmHg. The afferent renal nerve activity response to increased renal pelvic pressure was also enhanced by renal pelvic perfusion with 900 mM NaCl but was unaltered by NaCl concentrations ranging from 10 to 600 mM. These findings show that renal pelvic mechanoreceptors are activated by increases in renal pelvic pressure within the physiological range. Although renal Na(+)-K(+)-ATPase contributes to the maintenance of the resting membrane potential of renal pelvic mechanoreceptors, the renal pelvic mechanoreceptor discharge is not influenced by physiological renal pelvic Na+ concentrations.
A method for selective section of vagal afferent or efferent axons in the rat
Authors: Norgren R. , Smith G. P.
Published: December 2017

Although normally a mixed nerve, intracranially the vagus separates into dorsal rootlets that contain afferent axons and ventral rootlets that contain efferents. Surgical procedures are described for exposing the ventral surface of the occipital bone at the level where the vagus passes through the posterior lacerated foramen. When the foramen is expanded medially and the dura lanced, the intracranial course of the vagus can be observed by use of an operating microscope. Under these conditions, either the efferent or the afferent rootlets can be severed selectively. When the dorsal rootlets are divided and the contralateral trunk is cut below the diaphragm, a selective bilateral subdiaphragmatic afferent vagotomy is produced with unilateral sparing of the efferents. Cutting the efferents intracranially has the converse effect.
Ventral medullary surface activity during sleep, waking, and anesthetic states in the goat
Authors: Rector D. M. , Gozal D. , Forster H. V. , Ohtake P. J. , Pan L. G. , Lowry T. F. , Harper R. M.
Published: December 2017

We examined activity, measured as changes in reflected light, from the surface of a rostral ventral medullary area that is involved in cardiorespiratory control. We collected images during sleep and waking states and during halothane anesthesia in five adult unrestrained goats. During quiet sleep, overall activity increased and overall variability decreased compared with waking levels, whereas rapid eye movement sleep increased variability, and average activity decreased to near-waking levels. Distinct regions of activation and suppression appeared during sleep states. Deep anesthesia decreased activity and minimized variation. We speculate that alterations in rostral ventral medullary surface activity may play a role in state-dependent changes in cardiorespiratory control mechanisms.
Prolonged stimulation of intrarenal V1 vasopressin receptors results in sustained hypertension
Authors: Szczepanska-Sadowska E. , Stepniakowski K. , Skelton M. M. , Cowley A. W.
Published: December 2017

In an earlier study, we reported that chronic intravenous administration of the V1 agonist [Phe2,Ile3,Orn8]vasopressin (V1AG) results in sustained hypertension. The present study was designed to determine whether V1-induced hypertension may be related specifically to intrarenal actions of this peptide. Chronic infusion of the V1 agonist into the medullary interstitial space of a single remaining kidney of normal, conscious Sprague-Dawley rats at the rate of 2 ng.kg-1.min-1 for 14 days resulted in a sustained rise of 18 mmHg of mean arterial pressure (MAP). After withdrawal of V1AG, MAP returned to the baseline level. During the first day of V1AG infusion, there was a net loss of body sodium and no evidence of fluid retention throughout the period of hypertension. Plasma osmolality, sodium and potassium concentration, and water intake and body weight were not significantly affected by medullary interstitial infusion of V1AG. Renal medullary interstitial infusion of an equimolar amount of arginine vasopressin (AVP) did not affect MAP. Chronic medullary interstitial infusion of the selective V1 antagonist d(CH2)5[Tyr(Me)2,Ala-NH(2)9]AVP in equimolar amounts (2.5 ng.kg-1.min-1) prevented the MAP increase elicited by intravenous V1AG. However, intravenous administration of the V1 antagonist at the same rate together with V1AG (n = 7) failed to prevent hypertension. The results indicate that hypertension can be elicited by chronic stimulation of renal medullary V1 vasopressin receptors. They also suggest that some V2 agonistic properties of AVP may restrict the hypertensive action of this hormone. The mechanism for the rise of arterial pressure remains to be determined.
Developmental changes in cardiorespiratory patterns of sleep-associated apnea in northern elephant seals
Authors: Castellini M. A. , Rea L. D. , Sanders J. L. , Castellini J. M. , Zenteno-Savin T.
Published: December 2017

The development of heart rate and respiratory patterns related to sleep-associated apnea were studied in northern elephant seal (Mirounga angustirostris) pups and adult males. Heart rate patterns became more refined in conjunction with an age-related increase in apnea duration in pups. That is, older pups showed significant sinus arrhythmia, while breathing and apneic heart rate were both stable and similar in magnitude to the sinus arrhythmia minimum. By contrast, younger pups showed poor or nonexistent sinus arrhythmia and shorter apnea durations with a variable and/or high heart rate during apnea. Apnea duration was positively correlated with the development of sinus arrhythmia and negatively correlated with both eupneic and apneic heart rate. Adult males showed extremely well-developed patterns of sinus arrhythmia and, in all cases, the minimum heart rate during the sinus arrhythmia was lower than the average heart rate recorded during apnea. These results suggest that seal pups are not born with the cardiac control associated with voluntary long duration apnea, but that apnea tolerance increases with refined cardiorespiratory control.
Effects of chronic lard feeding on sympathetic nervous system activity in the rat
Authors: Young J. B. , Daly P. A. , Uemura K. , Chaouloff F.
Published: December 2017

The level of sympathetic nervous system (SNS) activity in obesity is controversial, with reports claiming either increased or decreased SNS activity. The following studies examined SNS activity in a dietary form of obesity, ingestion of a lard-enriched diet for 4 wk. Plasma norepinephrine (NE) levels were 61% higher in rats fed the lard-enriched diet than in chow-fed controls at 20 degrees C (200 +/- 24 pg/ml vs. 124 +/- 6, P < 0.005) and remained elevated after 1 h of cold exposure (4 degrees C). [3H]NE turnover was markedly increased in heart, but not in interscapular brown adipose tissue (IBAT), kidney, liver, skeletal muscle, or spleen of rats fed the high-fat diet. By contrast, ingestion of a diet similarly enriched with sucrose raised rates of [3H]NE turnover in IBAT as well as in heart. Thus chronic ingestion of a lard-enriched diet induces region-specific stimulation of SNS activity that is greater in heart than in IBAT. Whereas the absence of an SNS response to lard in IBAT may contribute to weight gain in these animals, activation of cardiac sympathetic nerves may promote development of hypertension in this model of obesity.
Insulin and insulin-like growth factor I in coho salmon Oncorhynchus kisutch injected with streptozotocin
Authors: Plisetskaya E. M. , Duan C.
Published: December 2017

Streptozotocin (STR), an agent known to induce damage of pancreatic B cells in mammals, was used to study changes of plasma insulin concentration and hepatic insulin-like growth factor I (IGF-I) mRNA levels in juvenile coho salmon, Oncorhynchus kisutch. Fish were injected intraperitoneally with either 200 mg/kg body wt STR or the vehicle. All fish fed and grew throughout the experiment; however, the STR-injected fish had lower instantaneous growth rates than control fish (1.4% and 2.1%, correspondingly). Plasma insulin concentration and hepatic IGF-I mRNA levels in STR-treated fish were significantly lower than in the control fish, whereas there was no difference between the two groups of fish in plasma concentrations of either glucagon or growth hormone. Impaired insulin production caused by STR injection was either coincident with or slightly preceded reduction in hepatic IGF-I mRNA expression, implying that insulin may affect IGF-I production and, consequently, fish growth.
Interaction between angiotensin II and nitric oxide in control of renal hemodynamics in conscious dogs
Authors: Alberola A. M. , Salazar F. J. , Nakamura T. , Granger J. P.
Published: December 2017

Recent in vitro studies have provided evidence that the vasoconstrictor actions of angiotensin II on afferent arterioles are enhanced by nitric oxide synthesis inhibition. Although these studies suggest that nitric oxide may play a role in protecting the afferent arterioles from angiotensin II-induced vasoconstriction, the importance of this interaction in the regulation of glomerular filtration rate and renal blood flow in the intact, conscious animal is not known. The objective of the present study was to determine the role of nitric oxide in modulating the renal hemodynamic and excretory effects of angiotensin II. Angiotensin II was infused at rates of 0.5, 1.0, and 2.0 micrograms.kg-1.min-1 intrarenally in conscious, chronically instrumented dogs in both the presence and absence of nitric oxide synthesis inhibition by continuous intrarenal infusion of NG-nitro-L-arginine methyl ester (3 micrograms.kg-1.min-1). At a dose of 0.5 micrograms.kg-1.min-1, angiotensin II decreased renal plasma flow by 19%, while having no effect on glomerular filtration rate in control dogs. In contrast, angiotensin II decreased renal plasma flow by 54%, glomerular filtration rate by 40%, and increased renal vascular resistance by 125% in the presence of intrarenal nitric oxide synthesis blockade. At doses of 1.0 and 2.0 micrograms.kg-1.min-1, angiotensin II reduced renal plasma flow by 36 and 45%, glomerular filtration rate by 17 and 23%, and increased renal vascular resistance by 80 and 120%, respectively, in control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Cholecystokinin reduces sucrose palatability in rats: evidence in support of a satiety effect
Authors: Eckel L. A. , Ossenkopp K. P.
Published: December 2017

To investigate the hypothesis that peripherally administered cholecystokinin (CCK) reduces food intake by the production of aversive internal cues, we examined the effects of the sulfated, octapeptide form of CCK on taste reactivity responses to oral sucrose infusions in male rats implanted with intraoral cannulas. After injection of CCK (4, 8, or 16 micrograms/kg ip) or 0.15 M saline (1 ml/kg ip), a series of brief (30 s) intraoral infusions of a 0.30 M sucrose solution was administered at 2-min intervals for 10 min. All doses of CCK were found to significantly decrease ingestive responding during the first and subsequent sucrose infusions without promoting a significant increase in aversive responses relative to controls. The lack of a gradual, conditioned shift in taste reactivity responses, from an ingestive to an aversive pattern (which is typically observed after LiCl administration), suggests that the production of nausea-like aversive internal cues was likely not responsible for the observed CCK-induced alterations in taste reactivity responses. It appears that the unconditioned, satiogenic effects of CCK contributed to the selective reduction in ingestive responses observed in the present study.
Ventilatory and metabolic responses to hypoxia in the echidna, Tachyglossus aculeatus
Authors: Frappell P. B. , Franklin C. E. , Grigg G. C.
Published: December 2017

Oxygen consumption (VO2), CO2 production (VCO2), and minute ventilation (VE) together with breathing pattern were measured in echidnas during normoxia and hypoxia. In normoxia, VO2, VCO2, and VE were all found to be approximately 30% of the allometric prediction for a eutherian. As a consequence VE/VO2 and VE/VCO2 are as predicted for a mammal. This is in contrast to previous reports on the echidna in which the VE was shown to be low and the echidna, subsequently, to be in a state of hypoventilation. It is possible that the difference between this and previous studies is related to the resting state of the echidna; echidnas in this study adopted a curled-up "sleeping" posture, and measurements were made without tactile disturbance. Breathing pattern was typical of a semifossorial species in that inspiration time to total breath time was short when compared with the normal eutherian value. In graded hypoxia VE increased [threshold fractional concentration of inspired O2 (FIO2) = 0.125], predominantly the result of changes in frequency achieved through a shortening in expiration time. In acute hypoxia (FIO2 = 0.10) VE/metabolic rate showed a tendency to increase, mainly because of the increase in VE. Approximately 50% of the increase in VE could be attributed to the 25% increase in VO2 and VCO2 that occurred in acute hypoxia. Given that the general mammalian response to hypoxia is a drop in metabolic rate, possible reasons as to why the echidna does not decrease metabolic rate in hypoxia are discussed.
Does the histaminergic system mediate bombesin/GRP-induced suppression of food intake?
Authors: Merali Z. , Banks K.
Published: December 2017

Bombesin (BN) and its mammalian homologue, gastrin-releasing peptide (GRP), are potent satiety agents and have been implicated in the physiological regulation of food intake. The mechanism(s) of action of this effect remains unclear. There is a functional and anatomic overlap between histamine and BN in relationship to feeding, which led us to hypothesize that BN may mediate its satiety effects through activation of the histaminergic system. To assess this contention, we examined the effects of R-alpha-methylhistamine (alpha-MH) and Imetit, selective H3-receptor agonists that inhibit the release and synthesis of histamine, on BN- or cholecystokinin (CCK)-induced satiety. In this report we present the first evidence for the role of histamine H3 receptors in the mediation of BN-elicited satiety. During the first hour of the 4-h daily feeding session, BN reduced food intake by > 50% relative to the control condition; this suppression was blocked by prior treatment with the H3-receptor agonist, alpha-MH. This blockade of BN-induced satiety was dose related and selective to BN as alpha-MH failed to attenuate sulfated CCK-8-induced satiety. When alpha-MH was administered alone, it failed to significantly affect food intake. The specificity of this effect was further supported by the demonstration that another H3 agonist, Imetit, was also able to block the feeding-suppressant effects of BN. Furthermore, thioperamide, an H3-receptor antagonist, blocked these effects of Imetit.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of acute phase responses induced in rabbits by lipopolysaccharide and double-stranded RNA
Authors: Kimura M. , Toth L. A. , Agostini H. , Cady A. B. , Majde J. A. , Krueger J. M.
Published: December 2017

Infection of injury results in several systemic and central reactions termed the acute phase response (APR). Substantial evidence suggests that cytokines induced by microbes initiate the APR. We compared the APR induced in rabbits by a model bacterial stimulus, lipopolysaccharide (LPS), to that induced by a model viral stimulus, polyriboinosinic:polyribocytidylic acid (poly I:C). The cytokine mRNA responses in a mouse macrophage cell line (RAW 264.7) to LPS or poly I:C were also determined. Rabbits were injected intravenously or intracerebroventricularly with different doses of LPS or poly I:C. Colonic temperatures (Tco) and blood samples were taken at the time of injection and at 3, 6, and 24 h after injection. Leukocyte numbers, serum antiviral activity, serum ceruloplasmin, and plasma fibrinogen were analyzed. Both intravenously injected LPS and poly I:C increased Tco, decreased leukocytes, and increased ceruloplasmin. Only LPS by the intravenous route increased fibrinogen, whereas only intravenously injected poly I:C induced antiviral activity. Intracerebroventricular injections of LPS and poly I:C also elicited dose-dependent febrile responses but did not change the hematologic APR significantly except for fibrinogen. The primary distinctions between LPS and poly I:C with respect to cytokine induction in the RAW 264.7 macrophage cell line were that LPS failed to induce interferon (IFN)-alpha, poly I:C induced interleukin (IL)-6 mRNA minimally and for a shorter time period than did LPS, and LPS induced IL-1 alpha and IFN-beta more rapidly than did poly I:C.(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin and Na-dependent alanine transport in skeletal muscle of obese Zucker (fa/fa) rats
Authors: King P. A. , Betts J. J.
Published: December 2017

Obese Zucker (fa/fa) rat skeletal muscle is characterized by a reduced rate of muscle protein deposition possibly due to alterations in amino acid transport. The purpose of the present study was to investigate alanine transport in plasma membrane vesicles from skeletal muscle of lean and obese Zucker rats, facilitating the study of alanine transport independent of cellular metabolism. Initial rates of alanine transport were measured in the presence and absence of Na using a rapid filtration technique, and the properties of membranes from control and maximally insulin-treated lean and obese Zucker rats were studied. For lean rats, the maximal stimulation (Vmax) for Na-dependent alanine transport was 207 pmol.mg-1.s-1, and the half-maximal affinity constant (K1/2) was 2.3 mM. Insulin treatment increased the Vmax to 387 pmol.mg-1.s-1 with no changes in K1/2. For the obese rats, the Vmax for Na-dependent alanine transport was 248 pmol.mg-1.s-1, and the K1/2 was 2.8 mM. These values were not changed by insulin treatment. Thus Na-dependent alanine transport in obese rat skeletal muscle is resistant to stimulation by insulin; this alteration may contribute to the abnormal muscle protein metabolism observed in these animals.
Pathogenesis of hyponatremia in an experimental model of the syndrome of inappropriate antidiuresis
Authors: Verbalis J. G.
Published: December 2017

Rats were infused with a selective agonist of vasopressin V2 receptors (1-desamino-D-arginine vasopressin; DDAVP) at two different doses (1 or 5 ng/h) and fed a liquid formula to produce both moderate (plasma [Na+] = 119-124 mmol/l) and severe (plasma [Na+] = 106-112 mmol/l) hyponatremia. Whole body water and electrolyte contents were analyzed after 1, 7, and 14 days of hyponatremia to assess the relative contributions from water retention and sodium depletion to hyponatremia of varying duration and severity. Body water of the hyponatremic rats was significantly increased over normonatremic control rats after 1 and 7 days; after 14 days, the 1 ng/h DDAVP-infused rats also had elevated body water, but the 5 ng/h DDAVP-infused rats returned to levels not significantly different from controls. Body Na+ and Cl- both decreased significantly after 1 day of hyponatremia, and these decreases were sustained for 14 days; measured decreases were significantly greater in the more hyponatremic rats compared with the less hyponatremic rats. Body K+ of the 1 ng/h DDAVP-infused rats was not different from control rats, but significant K+ decreases occurred in the 5 ng/h DDAVP-infused rats after 7 and 14 days. Analysis of the measured plasma Na+ concentrations vs. those predicted by the changes in body water and sodium showed that both water retention and sodium losses were necessary to predict the final plasma [Na+]. However, the relative contribution from each varied with the duration of induced hyponatremia: acutely, water retention was the major cause of decreased plasma [Na+], but sodium depletion became predominant with longer periods of sustained hyponatremia.
Dopamine or transmitter release from rat carotid body may not be essential to hypoxic chemoreception
Authors: Sun M. K. , Reis D. J.
Published: December 2017

In anesthetized, paralyzed, and ventilated rats, hypoxia or intracarotid cyanide excited the carotid chemoafferents, whereas intracarotid dopamine and tyramine inhibited the chemoafferent discharges. The inhibition was abolished by chlorpromazine without attenuating the hypoxic excitation. Comparably, the hypoxic excitation was not attenuated by the following: 1) inhibition of nitric oxide synthase with NG-nitro-L-arginine; 2) inhibition of heme oxygenase with zinc protoporphyrin IX; 3) antagonism of ATP receptors with reactive blue 2; 4) antagonism of cholinergic receptors with atropine or trimethaphan; 5) inactivation of adenosine with adenosine deaminase; and 6) blockade of glutamate receptors with kynurenate. Systemic administration of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N'N'-tetraacetic acid, in doses reversibly blocking sympathetic ganglionic transmission, was also without effect. Cyanide microinjection (0.05-0.5 nmol) into the petrosal but not nodose ganglion elicited a rapid dose-dependent elevation of arterial pressure. We conclude that excitation of the chemoreceptor afferents by hypoxia/cyanide cannot be attributed to release of these agents nor to others by Ca(2+)-dependent mechanisms. The results suggest that the afferent nerves themselves might function as oxygen detectors.