bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic consequences of a species difference in Gibbs free energy of Na+/Ca2+exchange: rat versus guinea pig
Authors: Cooper P. J. , Ward M.-L. , Hanley P. J. , Denyer G. R. , Loiselle D. S.
Published: December 2017

The Gibbs free energy of the sarcolemmal Na+/Ca2+exchanger (ΔGNa/Ca) determines its net Ca2+flux. We tested the hypothesis that a difference of diastolic ΔGNa/Caexists between rat and guinea pig myocardium. We measured the suprabasal rate of oxygen consumption (Vo2) of arrested Langendorff-perfused hearts of both species, manipulating ΔGNa/Caby reduction of extracellular Na+concentration, [Na+]o. Hill equations fitted to the resulting Vo2-[Na+]orelationships yielded Michaelis constant ( Km) values of 67 and 25 mM for rat and guinea pig, respectively. We developed and tested a simple thermodynamic model that attributes this difference of Kmvalues to a 7.84 kJ/mol difference of ΔGNa/Ca. The model predicts that reversal of Na+/Ca2+exchange, leading to diastolic Ca2+influx, should occur at a value of [Na+]oabout three times higher in rat myocardium. We verified this quantitative prediction using fura 2 fluorescence to index intracellular Ca2+concentration in isolated ventricular trabeculae at 37°C. The postulated difference in free energy of Na+/Ca2+exchange explains a number of reported disparities of Ca2+handling at rest between rat and guinea pig myocardia.
Sites of respiratory rhythmogenesis during development in the tadpole
Authors: Torgerson C. S. , Gdovin M. J. , Remmers J. E.
Published: December 2017

During ontogeny, amphibian larvae experience a dramatic alteration in the motor act of breathing as the premetamorphic gill breather develops into the postmetamorphic lung ventilator. We tested the hypothesis that the site of lung rhythmogenesis relocates during metamorphosis by recording fictive lung ventilation before and after transecting the in vitro brain stem of pre- and postmetamorphic Rana catesbeiana into four segments. In premetamorphic tadpoles, the two caudalmost brain stem segments combined proved to be the minimum brain stem configuration necessary and sufficient for lung burst generation. In the postmetamorphic counterpart, this function was supplied by the combination of the two rostralmost brain stem segments. In the postmetamorphic brain stem, a 500-μm segment lying just rostral to cranial nerve IX conveys rhythmogenic capability to neighboring rostral or caudal segments. We conclude that lung rhythmogenic capability translocates rostrally during development as the tadpole shifts from gill to lung ventilation.
Expression of myogenic constrictor tone in the aorta of hypertensive rats
Authors: Rapacon-Baker Michelle , Zhang Fan , Pucci Michael L. , Guan Hui , Nasjletti Alberto
Published: December 2017

We investigated the effect of intraluminal pressure or stretch on the development of tone in the descending thoracic aorta from rats with aortic coarctation-induced hypertension of 7–14 days duration. Increments of pressure >100 mmHg decreased the diameter of thoracic aortas from hypertensive but not from normotensive rats. The pressure-induced constriction was not demonstrable in vessels superfused with calcium-free buffer. Stretched rings of aorta from hypertensive rats exhibited a calcium-dependent constrictor tone accompanied by elevated calcium influx that varied in relation to the degree of stretch. Blockers of l-type calcium channels and inhibitors of protein kinase C reduced both basal tone and calcium influx in aortic rings of hypertensive rats. Hence, the thoracic aorta of hypertensive rats expresses a pressure- and stretch-activated constrictor mechanism that relies on increased calcium influx throughl-type calcium channels via a protein kinase C-regulated pathway. The expression of such a constrictor mechanism is suggestive of acquired myogenic behavior.
Defense reaction alters the response to blood loss in the conscious rabbit
Authors: Schadt James C. , Hasser Eileen M.
Published: December 2017

The interaction of sensory stressors with the cardiovascular response to blood loss has not been studied. The cardiovascular response to a stressor (i.e., the defense reaction) includes increased skeletal muscle blood flow and perhaps a reduction in arterial baroreflex function. Arterial pressure maintenance during blood loss requires baroreflex-mediated skeletal muscle vasoconstriction. Therefore, we hypothesized that the defense reaction would limit arterial pressure maintenance during blood loss. Male, New Zealand White rabbits were chronically prepared with arterial and venous catheters and Doppler flow probes. We removed venous blood in conscious rabbits until mean arterial pressure decreased to <40 mmHg. We repeated the experiment with (air) and without (sham) simultaneous exposure to an air jet stressor. Air resulted in a defense reaction (e.g., mean arterial pressure = 94 ± 1 and 67 ± 1 mmHg for air and sham, respectively). Contrary to our hypothesis, air increased the blood loss necessary to produce hypotension (19.3 ± 0.2 vs. 16.9 ± 0.2 ml/kg for sham). Air did not reduce skeletal muscle vasoconstriction during normotensive hemorrhage. However, air did enhance renal vasoconstriction (97 ± 3 and 59 ± 3% of baseline for sham and air, respectively) during the normotensive phase. Thus the defense reaction did not limit but rather extended defense of arterial pressure during hemorrhage.
Injection of muscimol in dorsomedial hypothalamus and stress-induced Fos expression in paraventricular nucleus
Authors: Morin S. M. , Stotz-Potter E. H. , Dimicco J. A.
Published: December 2017

Prior microinjection of the GABAA-receptor agonist muscimol into the dorsomedial hypothalamus (DMH) in conscious rats attenuates the increases in heart rate, blood pressure, and circulating adrenocorticotrophic hormone seen in air stress. Here, we examined the effect of similar treatment on air stress- or hemorrhage-induced Fos expression in the paraventricular nucleus (PVN). Muscimol (80 pmol/100 nl per side) or saline (100 nl per side) was microinjected bilaterally into the DMH in conscious rats before either air stress, an emotional or neurogenic stressor, or graded hemorrhage, a physiological stressor. Each stressor evoked a characteristic pattern of Fos expression in the parvocellular and magnocellular PVN after saline. Injection of muscimol into the DMH suppressed Fos expression in the PVN associated with air stress but not with hemorrhage. Injection of muscimol at sites anterior to the DMH and closer to the PVN had no effect on Fos expression in the PVN after air stress. Thus activation of neurons in the DMH is necessary for excitation of neurons in the PVN during air stress but not during hemorrhage.
Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo
Authors: Matsuo Isamu , Hirooka Yoshitaka , Hironaga Kiyoshi , Eshima Kenichi , Shigematsu Hideaki , Shihara Miwako , Sakai Koji , Takeshita Akira
Published: December 2017

Nitric oxide (NO) in the nucleus tractus solitarii (NTS) plays an important role in regulating sympathetic nerve activity. The aims of this study were to determine whether the activation of N-methyl-d-aspartate (NMDA) receptors in the NTS facilitates the release ofl-glutamate (Glu) via NO production, and, if so, to determine whether this mechanism is involved in the depressor and bradycardic responses evoked by NMDA. We measured the production of NO in the NTS as NO[Formula: see text] and NO[Formula: see text](NOx) or Glu levels by in vivo microdialysis before, during, and after infusion of NMDA in anesthetized rats. We also examined effects of Nω-nitro-l-arginine methyl ester (l-NAME) on the changes in these levels. NMDA elicited depressor and bradycardic responses and increased the levels of NOxand Glu. l-NAME abolished the increases in the levels of NOxand Glu and attenuated cardiovascular responses evoked by NMDA. These results suggest that NMDA receptor activation in the NTS induces Glu release through NO synthesis and that Glu released via NO enhances depressor and bradycardic responses.
Interaction of serotonin and cholecystokinin in the lateral parabrachial nucleus to control sodium intake
Authors: Fratucci De Gobbi Juliana Irani , De Luca Laurival Antonio , Johnson Alan Kim , Menani José Vanderlei
Published: December 2017

Serotonin [5-hydroxytryptamine (5-HT)] and CCK injected into the lateral parabrachial nucleus (LPBN) inhibit NaCl and water intake. In this study, we investigated interactions between 5-HT and CCK into the LPBN to control water and NaCl intake. Male Holtzman rats with cannulas implanted bilaterally in the LPBN were treated with furosemide + captopril to induce water and NaCl intake. Bilateral LPBN injections of high doses of the 5-HT antagonist methysergide (4 μg) or the CCK antagonist proglumide (50 μg), alone or combined, produced similar increases in water and 1.8% NaCl intake. Low doses of methysergide (0.5 μg) + proglumide (20 μg) produced greater increases in NaCl intake than when they were injected alone. The 5-HT2a/2c agonist 2,5-dimetoxy-4-iodoamphetamine hydrobromide (DOI; 5 μg) into the LPBN reduced water and NaCl intake. After proglumide (50 μg) + DOI treatment, the intake was not different from vehicle treatment. CCK-8 (1 μg) alone produced no effect. CCK-8 combined with methysergide (4 μg) reduced the effect of methysergide on NaCl intake. The data suggest that functional interactions between 5-HT and CCK in the LPBN may be important for exerting inhibitory control of NaCl intake.
Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection
Authors: Fang L. , Nowicki B. , Yallampalli C.
Published: December 2017

Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-α protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-α protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-α after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and that the constitutively elevated uterine NO during pregnancy may help contain or even reduce the risk of infection-related complications.
Vagal and spinal mechanosensors in the rat stomach and colon have multiple receptive fields
Authors: Berthoud Hans-Rudolf , Lynn Penny A. , Blackshaw L. Ashley
Published: December 2017

Mechano- and chemosensitive extrinsic primary afferents innervating the gastrointestinal tract convey important information regarding the state of ingested nutrients and specific motor patterns to the central nervous system via splanchnic and vagal nerves. Little is known about the organization of peripheral receptive sites of afferents and their correspondence to morphologically identified terminal structures. Mechano- and chemosensory characteristics and receptive fields of single vagal fibers innervating the stomach as well as lumbar splanchnic nerves innervating the distal colon were identified using an in vitro perifusion system. Twenty-three (17%) of one-hundred thirty-six vagal units identified were found to have multiple, punctate receptive fields, up to 35 mm apart, and were distributed throughout the stomach. Evidence was based on similarity of generated spike forms, occlusion, and latency determinations. Most responded with brief bursts of activity to mucosal stroking with von Frey hairs (10–200 mg) but not to stretch, and 32% responded to capsaicin (10−5M). They were classified as rapidly adapting mucosal receptors. Four (8%) of fifty-three single units recorded from the lumbar splanchnic nerve had more than one, punctate receptive field in the distal colon, up to 40 mm apart. They responded to blunt probing, particularly from the serosal side, and variously to chemical stimulation with 5-hydroxytryptamine and capsaicin. We conclude that a proportion of gastrointestinal mechanosensors has multiple receptive fields and suggest that they integrate mechanical and chemical information from an entire organ, constituting the generalists in visceral sensation.
Intestinal satiety protein apolipoprotein AIV is synthesized and regulated in rat hypothalamus
Authors: Liu Min , Doi Takashi , Shen Ling , Woods Stephen C. , Seeley Randy J. , Zheng Shuqin , Jackman Alana , Tso Patrick
Published: December 2017

Apolipoprotein AIV (apo AIV) is a satiety protein secreted by the small intestine. We demonstrate for the first time that apo AIV protein and apo AIV mRNA are present in rat hypothalamus, a site intimately involved in the integration of signals for regulation of food intake and energy metabolism. We further characterized the regulation of hypothalamic apo AIV mRNA levels. Food-deprived animals showed a pronounced decrease in gene expression of apo AIV in the hypothalamus, with a concomitant decrease in the jejunum. Refeeding fasted rats with standard laboratory chow for 4 h evokes a significant increase of apo AIV mRNA in jejunum but not in hypothalamus. However, lipid refeeding to the fasted animals restored apo AIV mRNA levels both in hypothalamus and jejunum. Intracerebroventricular administration of apo AIV antiserum not only stimulated feeding, but also decreased apo AIV mRNA level in the hypothalamus. These data further confirm the central role of apo AIV in the regulation of food intake.
Role of spinal α1-adrenoceptor subtypes in the bladder reflex in anesthetized rats
Authors: Yoshiyama Mitsuharu , De Groat William C.
Published: December 2017

The contribution of different subtypes of α1-adrenoceptors in the lumbosacral spinal cord to the control of the urinary bladder was examined in urethane-anesthetized rats. Bladder pressure was recorded via a transurethral catheter under isovolumetric conditions. Drugs were administered intrathecally at the L6-S1segmental level of spinal cord. RS-100329 (an α1A-antagonist) in doses of 25, 50, and 100 nmol significantly decreased bladder-contraction amplitude by 38%, 52%, and 95%, respectively, whereas (+)-cyclazosin (an α1B-antagonist) significantly decreased bladder-contraction amplitude (48% reduction) only in a 50-nmol but not a 100-nmol dose. Fifty nanomoles of RS-100329 and (+)-cyclazosin increased bladder-contraction frequency by 54% and 44%, respectively. BMY7378 (an α1D-antagonist), in doses of 25, 50, and 100 nmol, did not change bladder activity. These studies suggest that reflex-bladder activity is modulated by two types of spinal α1-adrenergic mechanisms: 1) α1A- or α1B-inhibitory control of the frequency of voiding reflexes presumably mediated by an alteration in the processing of bladder afferent input and 2) α1A-facilitatory modulation of the descending efferent limb of the micturition-reflex pathway. Spinal α1D-adrenoceptors do not appear to have a significant role at either site.
L-364,718, a cholecystokinin-A receptor antagonist, suppresses feeding-induced sleep in rats
Authors: Shemyakin Alexei , Kapás Levente
Published: December 2017

Feeding induces increased sleep in several species, including rats. The aim of the study was to determine if CCK plays a role in sleep responses to feeding. We induced excess eating in rats by 4 days of starvation and studied the sleep responses to refeeding in control and CCK-A receptor antagonist-treated animals. Sleep was recorded on 2 baseline days when food was provided ad libitum. After the starvation period, sleep was recorded on 2 refeeding days when the control rats ( n = 8) were injected with vehicle and the experimental animals ( n = 8) received intraperitoneal injections of L-364,718 (500 μg/kg, on both refeeding days). In the control group, refeeding caused increases in rapid eye movement sleep (REMS) and non-REMS (NREMS) and decreases in NREMS intensity as indicated by the slow-wave activity (SWA) of the electroencephalogram. CCK-A receptor antagonist treatment completely prevented the SWA responses and delayed the NREMS responses to refeeding; REMS responses were not simply abolished, but the amount of REMS was below baseline after the antagonist treatment. These results suggest that endogenous CCK, acting on CCK-A receptors, may play a key role in eliciting postprandial sleep.
Acupuncture effects on reflex responses to mental stress in humans
Authors: Middlekauff Holly R. , Yu Jun Liang , Hui Kakit
Published: December 2017

In animal studies, acupuncture has been shown to be sympathoinhibitory, but it is unknown if acupuncture is sympathoinhibitory in humans. Nineteen healthy volunteers underwent mental stress testing pre- and postacupuncture. Muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate during mental stress were compared pre- and postacupuncture. Control acupuncture consisted of acupuncture at nonacupoints and “no-needle” acupuncture. Acupuncture had no effect on resting MSNA, blood pressure, or heart rate. After real acupuncture, the increase in mean arterial pressure (pre- vs. postacupuncture 4.5 vs. 1.7 mmHg, P < 0.001), but not MSNA or heart rate, was blunted during mental stress. Similarly, following nonacupoint acupuncture, the increase in mean arterial pressure was blunted during mental stress (5.4 vs. 2.9 mmHg, P < 0.0003). No-needle acupuncture had no effect on these variables.

In conclusion, acupuncture at traditional acupoints, nonacupoints, and no-needle acupuncture does not modulate baseline MSNA or MSNA responses to mental stress in normal humans. Acupuncture significantly attenuates the increase in blood pressure during mental stress. Needling nonacupoints, but not “no-needle” acupuncture, have a similar effect on blood pressure.
Melatonin enhancement of splenocyte proliferation is attenuated by luzindole, a melatonin receptor antagonist
Authors: Drazen Deborah L. , Bilu Donna , Bilbo Staci D. , Nelson Randy J.
Published: December 2017

In addition to marked seasonal changes in reproductive, metabolic, and other physiological functions, many vertebrate species undergo seasonal changes in immune function. Despite growing evidence that photoperiod mediates seasonal changes in immune function, little is known regarding the neuroendocrine mechanisms underlying these changes. Increased immunity in short days is hypothesized to be due to the increase in the duration of nightly melatonin secretion, and recent studies indicate that melatonin acts directly on immune cells to enhance immune parameters. The present study examined the contribution of melatonin receptors in mediating the enhancement of splenocyte proliferation in response to the T cell mitogen Concanavalin A in mice. The administration of luzindole, a high-affinity melatonin receptor antagonist, either in vitro or in vivo significantly attenuated the ability of in vitro melatonin to enhance splenic lymphocyte proliferation during the day or night. In the absence of melatonin or luzindole, splenocyte proliferation was intrinsically higher during the night than during the day. In the absence of melatonin administration, luzindole reduced the ability of spleen cells to proliferate during the night, when endogenous melatonin concentrations are naturally high. This effect was not observed during the day, when melatonin concentrations are low. Taken together, these results suggest that melatonin enhancement of splenocyte proliferation is mediated directly by melatonin receptors on splenocytes and that there is diurnal variation in splenocyte proliferation in mice that is also mediated by splenic melatonin receptors.
Melatonin or a melatonin agonist corrects age-related changes in circadian response to environmental stimulus
Authors: Van Reeth Olivier , Weibel Laurence , Olivares Elisabeth , Maccari Sonia , Mocaer Elisabeth , Turek Fred William
Published: December 2017

The effects of a melatonin agonist, S-20098, included in the diet were tested on a specific effect of aging in hamsters: the marked decline in the phase shifting effects of a 6-h pulse of darkness on a background of constant light. In contrast to young hamsters, old hamsters fed with the control diet showed little or no phase shifts in response to a dark pulse presented in the middle of their inactive or active period. Old hamsters fed with S-20098 showed phase shifts that were ∼70% of the ones in young animals and significantly greater than those in old controls. The phase advancing response to a dark pulse presented during the inactive period was dose dependent and reversed after S-20098 discontinuation. Melatonin included in the diet showed comparable restorative effects on the phase shifting response to a dark pulse in old hamsters. Replacement therapy with melatonin or melatonin-related compounds could prove useful in treating, preventing, or delaying disturbances of circadian rhythmicity and/or sleep in older people.
Enhancement of REM sleep during extraocular light exposure in humans
Authors: Murphy Patricia J. , Campbell Scott S.
Published: December 2017

This study examined the effects on sleep of light administered to an extraocular site. A 3-h photic stimulus was applied to the popliteal region during sleep in 14 human subjects. Each subject also underwent a control stimulus condition during a separate laboratory session. The proportion of rapid eye movement (REM) sleep during the 3-h light administration session increased by an average of 31% relative to the control condition. The frequency but not the duration of REM episodes was altered during light exposure, thereby shortening the REM/non-REM (NREM) cycle length. No other sleep stages were significantly affected during light administration nor was sleep architecture altered after the light-exposure interval. These results confirm that extraocular light is transduced into a signal that is received and processed by the human central nervous system. In addition, they expand to a novel sensory modality previous findings that REM sleep can be enhanced by sensory stimulation.
Intracerebroventricular CART peptide reduces rat ingestive behavior and alters licking microstructure
Authors: Aja Susan , Schwartz Gary J. , Kuhar Michael J. , Moran Timothy H.
Published: December 2017

Intracerebroventricular administration of cocaine- and amphetamine-regulated transcript (CART) peptides reduces food intake and increases c-Fos in brain areas involved in the control of feeding. To discern behavioral mechanisms through which CART alters the microstructure of feeding, we injected CART-(55–102) (0.1, 0.5, 1, 2 μg, and saline controls) into the lateral ventricle of male Sprague-Dawley rats 5 min before dark onset and, using lickometers, monitored the ingestion of an Ensure liquid diet for the first 6 h of dark. At a threshold dose of 1 μg, CART dose dependently 1) decreased intake of Ensure in licks; 2) decreased meal size, but did not alter meal duration or number; 3) reduced initial lick rate of meals; and 4) significantly reduced burst number, licks/burst, and licks/cluster. CART dose dependently increased interlick interval (0.5 μg threshold, 192 ± 4 vs. 183 ± 3 ms, control; 1 μg: 201 ± 1 ms; 2 μg: 214 ± 6 ms). These data suggest that altered oral motor function, and possibly palatability perception, may be fundamental to the anorexigenic action of CART.
Muscarinic modulation of GABAergic transmission to neurons in the rat subfornical organ
Authors: Xu Sheng-Hong , Honda Eiko , Ono Kentaro , Inenaga Kiyotoshi
Published: December 2017

Cholinergic actions on subfornical organ (SFO) neurons in rat slice preparations were studied by using whole cell voltage- and current-clamp recordings. In the voltage-clamp recordings, carbachol and muscarine decreased the frequency of GABAergic inhibitory postsynaptic currents (IPSCs) in a dose-dependent manner, with no effect on the amplitudes or the time constants of miniature IPSCs. Meanwhile, carbachol did not influence the amplitude of the outward currents induced by GABA. Furthermore, carbachol and muscarine also elicited inward currents in a TTX-containing solution. From the current-voltage relationship, the reversal potential was estimated to be −7.1 mV. These carbachol-induced responses were antagonized by atropine. In the current-clamp recordings, carbachol depolarized the membrane with increased frequency of action potentials. These observations suggest that acetylcholine suppresses GABA release through muscarinic receptors located on the presynaptic terminals. Acetylcholine also directly affects the postsynaptic membrane through muscarinic receptors, by opening nonselective cation channels. A combination of these presynaptic and postsynaptic actions may enhance activation of SFO neurons by acetylcholine.
Hypothesis testing of the aging male gonadal axis via a biomathematical construct
Authors: Keenan Daniel M. , Veldhuis Johannes D.
Published: December 2017

Neuroendocrine axes are feedback- and feedforward-coupled dynamic ensembles. Disruption of selected pathways in such networklike organizations may explicate loss of orderly hormonal output as observed in aging. To test this notion more explicitly, we implemented an earlier computer-assisted biomathematical model of the interlinked male hypothalamo [gonadotropin-releasing hormone (GnRH)]-pituitary [luteinizing hormone, (LH)]-testicular [Leydig cell testosterone (Te)] axis ( Am J Physiol Endocrinol Metab Physiol 275: E157–E176, 1988; Keenan D., W. Sun, and J. D. Veldhuis, SIAM J Appl Math 61: 934–965, 2000). Thereby, we appraise mechanistic hypotheses for more disorderly LH and Te secretion in aging men. We compare model predictions with monitored abnormalities in the older male, namely, irregular patterns of individual and synchronous LH and Te release, reduced 24-h rhythmic Te output, and variably elevated LH secretion. Among the mechanisms examined, the most parsimonious aging hypothesis would entail impaired LH feedforward on Te without or with attenuated Te feedback on GnRH/LH secretion. This investigative strategy should aid in exploring new postulates of disrupted feedback networks in pathophysiology.
Pregnancy alters cortisol feedback inhibition of stimulated ACTH: studies in adrenalectomized ewes
Authors: Keller-Wood Maureen , Wood Charles E.
Published: December 2017

These studies test the hypothesis that pregnancy alters the feedback effects of cortisol on stimulated ACTH secretion. Ewes were sham-operated (Sham), or adrenalectomized (ADX) at ∼108 days gestation and replaced with aldosterone (3 μg · kg−1· day−1) and with cortisol at either of two doses (ADX + 0.6 and ADX + 1 mg · kg−1· day−1); ewes were studied during pregnancy and postpartum. Mean cortisol levels produced in ADX ewes were similar to normal pregnant ewes (ADX+1) or nonpregnant ewes (ADX+0.6), respectively. Plasma ACTH concentrations in response to infusion of nitroprusside were significantly increased in the pregnant ADX+0.6 ewes (1,159 ± 258 pg/ml) relative to pregnant Sham ewes (461 ± 117 pg/ml) or the ADX+1 ewes (442 ± 215 pg/ml) or the same ewes postpartum (151 ± 69 pg/ml). Plasma ACTH concentrations were not significantly different among the groups postpartum. Increasing plasma cortisol to 20–30 ng/ml for 24 h before hypotension produced similar inhibition of ACTH in all groups. Pregnancy appears to decrease the effectiveness of low concentrations of cortisol to inhibit ACTH responses to hypotension.
Social stress induces glucocorticoid resistance in macrophages
Authors: Stark Jennifer L. , Avitsur Ronit , Padgett David A. , Campbell Kim A. , Beck F. Michael , Sheridan John F.
Published: December 2017

Stress-induced levels of plasma glucocorticoid hormones are known to modulate leukocyte function. These experiments examined the effects of a social stressor on the responsiveness of peripheral immune cells. Male mice experienced six evening cycles of social disruption (SDR), in which an aggressive male intruder was placed into their home cage for 2 h. Although circulating corticosterone was elevated in SDR mice, they had enlarged spleens and increased numbers of splenic leukocytes. Splenocytes from SDR and control mice were cultured with lipopolysaccharide and corticosterone. Cells from SDR mice exhibited decreased sensitivity to the antiproliferative effects of corticosterone, suggesting that the peripheral immune cells were resistant to glucocorticoids. In addition, SDR cells produced more interleukin (IL)-6. To determine which cell population was affected, we used antibody-labeled magnetic beads to deplete splenocyte suspensions of B cells or macrophages. Depletion of macrophages from SDR cultures, but not depletion of B cells, abolished both the corticosterone resistance and enhanced IL-6 secretion. These findings demonstrate that a psychosocial stressor induced glucocorticoid resistance in mouse splenic macrophages.
Cytokine- and microbially induced sleep responses of interleukin-10 deficient mice
Authors: Toth Linda A. , Opp Mark R.
Published: December 2017

Interleukin (IL)-1 and tumor necrosis factor (TNF) promote slow-wave sleep (SWS), whereas IL-10 inhibits the synthesis of IL-1 and TNF and promotes waking. We evaluated the impact of endogenous IL-10 on sleep-wake behavior by studying mice that lack a functional IL-10 gene. Under baseline conditions, C57BL/6-IL-10 knockout (KO) mice spent more time in SWS during the dark phase of the light-dark cycle than did genetically intact C57BL/6 mice. The two strains of mice showed generally comparable responses to treatment with IL-1, IL-10, or influenza virus, but differed in their responses to lipopolysaccharide (LPS). In IL-10 KO mice, LPS induced an initial transient increase and a subsequent prolonged decrease in SWS, as well as profound hypothermia. These responses were not observed in LPS-treated C57BL/6 mice. These data demonstrate that in the absence of endogenous IL-10, spontaneous SWS is increased and the impact of LPS on vigilance states is altered. Collectively, these observations support a role for IL-10 in sleep regulation and provide further evidence for the involvement of cytokines in the regulation of sleep.
Renal mRNA response to reduced perfusion pressure conserved despite denervation in mature ovine fetuses
Authors: Rosnes Jon S. , Valego Nancy , Wang Jin Juan , Perez Frank M. , Rose James C.
Published: December 2017

We hypothesized that renal denervation in mature ovine fetuses reduces renin mRNA response to 24 h of reduced renal perfusion pressure (RPP). Seven occluder (O) (132.4 ± 1.2 days gestation) and six control (C) (131.5 ± 1.2 days gestation) fetuses underwent left renal denervation. Postoperatively, O fetuses experienced 24 h of reduced RPP by suprarenal aortic occlusion. Femoral arterial blood pressure (FAB) and plasma active renin (pARC) and prorenin (pPRC) concentrations were obtained hourly for 6 h and at h 23 and 24. Renin mRNA was measured by RNase protection assay. We quantitated renin containing glomeruli by immunocytochemistry. Variables were compared by ANOVA. Mean O group FAB reduction from baseline was −6.60 ± 0.41 mmHg. pARC and pPRC increased with occlusion, renal ARC and renal PRC 1 did not increase with occlusion. No effect in renin mRNA or number of positive glomeruli was noted with denervation in the basal state; however, significant increases were noted in response to RPP irrespective of innervation status. In conclusion, 24 h or reduced RPP in mature ovine fetus increases renal renin mRNA and the immunocytochemical expression of renin. This response is conserved despite denervation.
Central angiotensin induction of fetal brain c-fos expression and swallowing activity
Authors: Xu Zhice , Glenda Calvario , Day Linda , Yao Jiaming , Ross Michael G.
Published: December 2017

The present study examined physiological and cellular responses to central application of ANG II in ovine fetuses and determined the fetal central ANG-mediated dipsogenic sites in utero. Chronically prepared near-term ovine fetuses (130 ± 2 days) received injection of ANG II (1.5 μg/kg icv). Fetuses were monitored for 3.5 h for swallowing activity, after which animals were killed and fetal brains were perfused for subsequent Fos staining. Intracerebroventricular ANG II significantly increased fetal swallowing in near-term ovine fetuses (1.1 ± 0.2 to 4.5 ± 1.0 swallows/min). The initiation of stimulated fetal swallowing activity was similar to the latency of thirst responses (drinking behavior) elicited by central ANG II in adult animals. ANG II evoked increased Fos staining in putative dipsogenic centers, including the subfornical organ, organum vasculosum of the lamina terminalis, and median preoptic nucleus. Intracerebroventricular injection of ANG II also caused c- fos expression in the fetal hindbrain. These results indicate that an ANG II-mediated central dipsogenic mechanism is intact before birth, acting at sites consistent with the dipsogenic neural network. Central ANG II mechanisms likely contribute to fetal body fluid and amniotic fluid regulation.
Spinal proerectile effect of oxytocin in anesthetized rats
Authors: Giuliano François , Bernabé Jacques , McKenna Kevin , Longueville Florence , Rampin Olivier
Published: December 2017

The spinal cord contains the neural network that controls penile erection. This network is activated by information from peripheral and supraspinal origin. We tested the hypothesis that oxytocin (OT), released at the lumbosacral spinal cord level by descending projections from the paraventricular nucleus, regulated penile erection. In anesthetized male rats, blood pressure and intracavernous pressure (ICP) were monitored. Intrathecal (it) injection of cumulative doses of OT and the selective OT agonist [Thr4,Gly7]OT at the lumbosacral level elicited ICP rises whose number, amplitude, and area were dose dependent. Thirty nanograms of OT and one-hundred nanograms of the agonist displayed the greatest proerectile effects. Single injections of OT also elicited ICP rises. Preliminary injection of a specific OT-receptor antagonist, hexamethonium, or bilateral pelvic nerve section impaired the effects of OT injected it. NaCl and vasopressin injected it at the lumbosacral level and OT injected it at the thoracolumbar level or intravenously had no effect on ICP. The results demonstrate that OT, acting at the lumbosacral spinal cord, elicits ICP rises in anesthetized rats. They suggest that OT, released on physiological activation of the PVN in a sexually relevant context, is a potent activator of spinal proerectile neurons.
Effect of 5α-pregnan-3α-ol-20-one on nitric oxide biosynthesis and plasma volume in rats
Authors: Lo F. , Kaufman S.
Published: December 2017

Plasma 5α-pregnan-3α-ol-20-one (pregnan) levels and nitric oxide (NO) biosynthesis increase during pregnancy. These factors have independently been implicated in the control of blood pressure and volume. We wished to determine whether pregnan might be responsible both for the increase in NO biosynthesis and for the increase in plasma volume observed during pregnancy. Virgin female Long-Evans rats were implanted with indwelling cannulas and maintained on a low nitrate/nitrite diet. After the rats recovered from surgery, 500 μg of pregnan or vehicle were given daily for 2 days. NO biosynthesis and plasma volume were measured in conscious animals before and after treatment. Pregnan caused a significant increase in NO biosynthesis (1.9 ± 0.8 μmol/24 h, n = 10) compared with the vehicle-treated control group (0.3 ± 0.4 μmol/24 h, n = 10, P < 0.05). Similarly, there was a significant increase in plasma volume in the pregnan-treated group (0.7 ± 0.2 ml/100 g, n = 11) compared with the vehicle-treated control group (0.2 ± 0.1 ml/100 g, n = 11, P < 0.05). These results confirm that pregnan can mimic pregnancy by its ability to increase both NO biosynthesis and plasma volume.
Chronic endothelin-1 blockade reduces sympathetic nerve activity in rabbits with heart failure
Authors: Liu J.-L. , Pliquett R. U. , Brewer E. , Cornish K. G. , Shen Y.-T. , Zucker I. H.
Published: December 2017

Endothelin-1 (ET-1) is elevated in chronic heart failure (CHF). In this study, we determined the effects of chronic ET-1 blockade on renal sympathetic nerve activity (RSNA) in conscious rabbits with pacing-induced CHF. Rabbits were chronically paced at 320–340 beats/min for 3–4 wk until clinical and hemodynamic signs of CHF were present. Resting RSNA and arterial baroreflex control of RSNA were determined. Responses were determined before and after the ET-1 antagonist L-754,142 (a combined ETAand ETBreceptor antagonist, n = 5) was administered by osmotic minipump infusion (0.5 mg · kg−1· h−1for 48 h). In addition, five rabbits with CHF were treated with the specific ETAreceptor antagonist BQ-123. Baseline RSNA (expressed as a percentage of the maximum nerve activity during sodium nitroprusside infusion) was significantly higher (58.3 ± 4.9 vs. 27.0 ± 1.0, P < 0.001), whereas baroreflex sensitivity was significantly lower in rabbits with CHF compared with control (3.09 ± 0.19 vs. 6.04 ± 0.73, P < 0.001). L-754,142 caused a time-dependent reduction in arterial pressure and RSNA in rabbits with CHF. In addition, BQ-123 caused a reduction in resting RSNA. For both compounds, RSNA returned to near control levels 24 h after removal of the minipump. These data suggest that ET-1 contributes to sympathoexcitation in the CHF state. Enhancement of arterial baroreflex sensitivity may further contribute to sympathoinhibition after ET-1 blockade in heart failure.
Tubuloglomerular feedback after nephron or ureteral obstruction
Authors: Tanner G. A.
Published: December 2017

The effects of 1 day of single nephron, unilateral ureteral (UUO), and bilateral ureteral (BUO) obstruction on tubuloglomerular feedback were studied in anesthetized rats. Stop-flow pressure (SFP) was measured as an index of glomerular capillary pressure before, during, and after loop of Henle microperfusion. Tubuloglomerular feedback (delta SFP) showed an increased sensitivity to low loop perfusion rates and an increased maximal response after 1 day of single nephron obstruction or relief of UUO. Tubuloglomerular feedback was not significantly different from normal after release of BUO. Whole kidney glomerular filtration rate (GFR) was about 10% of normal after release of ureteral obstruction, and single nephron glomerular filtration rate (SNGFR) averaged one-third of normal. Paired measurements of SNGFR from proximal and distal tubules revealed no significant differences in control or in BUO kidneys, but a significant proximal-distal SNGFR difference was observed after UUO. The results suggest that tubuloglomerular feedback does not significantly contribute to the low GFR after release of BUO; after release of UUO, approximately one-fourth of the fall in GFR may be due to activation of the feedback mechanism.
Sites of insulin and glucagon metabolism in the rabbit nephron
Authors: Nakamura R. , Hayashi M. , Emmanouel D. S. , Katz A. I.
Published: December 2017

Uptake and degradation of peptide hormones have been demonstrated in proximal convoluted tubules (PCT), but the contribution of other regions of the nephron to renal hormone metabolism is unknown. In the present study we used micromethods to determine for the first time the degradation of radiolabeled insulin and glucagon by each segment of the rabbit nephron and examined some characteristics of this process in proximal convoluted and cortical collecting tubules (CCT). Degradation of insulin (8-10 fmol . cm-1 . h-1) and glucagon (13-15 fmol . cm-1 . h-1) was maximal in proximal convoluted and straight tubules, but occurred to a substantial degree (approximately 25-30% of PCT) in all other segments of the nephron except the thin descending limb. In PCT degradation of both hormones was maximal at physiological pH, and competition studies suggested that it is brought about by both specific and nonspecific proteases. Most of the degrading activity (insulin, 86%; glucagon, 73%) was in the cytosol or could be eluted off the cell membrane or organelles. In the CCT, a representative segment of the distal nephron, the characteristics of insulin degradation were similar to those observed in the PCT, whereas glucagon degradation appeared to be due chiefly to nonspecific proteases. In conclusion, the metabolism of insulin and glucagon by isolated rabbit tubules occurs chiefly in the proximal convoluted and straight tubules, but up to one-third of the degrading capacity of the proximal nephron is also present in distal nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of volume depletion in the glycerol model of acute renal failure
Authors: Cushner H. M. , Barnes J. L. , Stein J. H. , Reineck H. J.
Published: December 2017

Previous studies have demonstrated significant volume depletion early in the course of glycerol-induced acute renal failure. In addition, it has been shown that acute volume expansion within 6 h of glycerol administration reverses the fall in inulin clearance but volume expansion 12-24 h after glycerol fails to restore that parameter to normal. The current studies were performed to determine whether chronic volume expansion would prevent the fall in inulin clearance normally observed 18-20 h after the insult. Inulin clearance was therefore compared 18-20 h after glycerol in hydropenic rats and in rats undergoing chronic volume expansion by the constant infusion of Ringer solution at a rate of 5 ml/h initiated at the time of the glycerol injection. Inulin clearance was well maintained in the latter group, averaging 1.77 compared with 0.22 ml/min in the hydropenic group. Renal histology revealed no difference in the degree of tubular necrosis between groups but did show a marked decrease in cast formation in the animals undergoing chronic volume expansion. To determine the possible significance of these casts, micropuncture studies were carried out to measure proximal tubular pressures. Under hydropenic conditions these pressures were not different control animals and rats receiving glycerol when studied 18-20 h after glycerol. Following acute volume expansion, however, glycerol-treated rats demonstrated significantly higher pressures than control rats. On the other hand, proximal tubular pressures were comparable in glycerol-treated and control animals receiving the chronic volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)
Contributions of glomerular and tubular mechanisms to antidiuresis in conscious domestic fowl
Authors: Stallone John N. , Braun Eldon J.
Published: December 2017

Pages F842-F850: John N. Stallone and Eldon J. Braun. “Contributions of glomerular and tubular mechanisms to antidiuresis in conscious domestic fowl.” An early version rather than the final version of this article was printed. The corrected article will appear in the June issue of the journal for substitution.
Synergistic action of angiotensin II on norepinephrine-induced prostaglandin release from rat glomeruli
Authors: Matsumura Y. , Ozawa Y. , Suzuki H. , Saruta T.
Published: December 2017

The effects of vasoactive substances on the release of prostaglandin (PG) and thromboxane (TX) from isolated rat glomeruli were investigated. The PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TXB2 release during 60 min into Krebs-Henseleit medium was assessed by radioimmunoassay following extraction. Norepinephrine (NE) stimulated PGE2 (from 2,117 +/- 117 to 3,968 +/- 182 pg X mg protein-1 X 60 min-1, P less than 0.01) at a concentration of 10(-4)M and PGF2 alpha (from 2,748 +/- 285 to 8,535 +/- 495 pg X mg protein-1 X 60 min-1, P less than 0.01) at a concentration of 10(-5)M. However, neither angiotensin II (ANG II) nor arginine vasopressin (AVP) affected the release of PG and TXB2 at concentrations up to 10(-5)M. In the presence of 10(-5) M NE, ANG II enhanced the release of PGE2 (from 3,307 +/- 207 to 6,865 +/- 469 pg X mg protein-1 X 60 min-1., P less than 0.01) and PGF2 alpha (from 3,652 +/- 252 to 6,612 +/- 388 pg X mg protein-1 X 60 min-1, P less than 0.01) at a concentration of 10(-8)M, whereas AVP lacked any similar effect. These results indicate that catecholamine acts as a major stimulant for the release of PG from isolated glomeruli via alpha-receptors. ANG II may work in cooperation with catecholamine, but AVP appears to play little role.
Platelet-activating factor mediates endotoxin-induced acute renal insufficiency in rats
Authors: Wang J. , Dunn M. J.
Published: December 2017

Platelet-activating factor (PAF) may contribute to the renal functional impairment of endotoxemia. We therefore examined 1) the effects of two specific PAF-receptor antagonists, L-653,150 and L-652,731, on endotoxin-induced acute renal insufficiency and 2) the renal hemodynamic actions of PAF in anesthetized postpartum Wistar rats. An intravenous injection of endotoxin at 150 micrograms/kg reduced glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) without a change in mean arterial pressure. L-653,150, 50 mg/kg orally, attenuated the endotoxin-induced fall in GFR, RPF, and FF. An intravenous injection of L-652,731, 0.3 mg/kg, followed by an infusion at 16 micrograms.kg-1. min-1 prevented the endotoxin-elicited reduction in GFR, RPF, and FF. L-652,731 also reversed the endotoxin-induced renal functional impairment. PAF, infused at 16 ng.kg-1.min-1 into the suprarenal aorta, reduced GFR, RPF, and FF without a significant change in renal arterial pressure. L-652,731 prevented the PAF-induced changes. In contrast, meclofenamate worsened the renal hemodynamic effects of PAF. We conclude that PAF may play an important role in mediating the endotoxin-induced acute hemodynamic renal insufficiency in rats with normotensive endotoxemia.
Asymmetry of plasma membrane lipid order in Madin-Darby Canine Kidney cells
Authors: Le Grimellec C. , Friedlander G. , Giocondi M. C.
Published: December 2017

Fluorescence anisotropy experiments have been done to estimate, in situ, the lipid order of the plasma membrane of polarized Madin-Darby Canine Kidney cells (MDCK) grown on glass cover slips and labeled by 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH), a specific marker of the plasma membrane of living cells. Fluorescence microscopy, back-exchange, and quenching experiments indicated that TMA-DPH labeled the highly ordered (r greater than or equal to 0.32, 37 degrees C) apical domain of the plasma membrane of confluent monolayers. Opening of tight junctions or addition of the probe to cell suspensions resulted in a homogeneous distribution of TMA-DPH over the cell surface and in a marked decrease in anisotropy (0.27 less than or equal to r less than or equal to 0.29) that was due neither to a direct effect of Ca2+ on the probe nor to a change in fluorescence lifetime. Our data indicate that the apical domain, likely the external leaflet, of the plasma membrane of polarized MDCK cells is much more ordered than its basolateral counterpart.