bluuebunny/crossref_metadata_2025 huggingface dataset:
Ontogeny of the arterial and cardiopulmonary baroreflex during fetal and postnatal life
Authors: Segar J. L.
Published: December 2017

The autonomic nervous system is intimately involved in regulating cardiovascular function. Sensing mechanisms dispersed throughout the circulation, including arterial baroreceptors, low pressure receptors, and chemosensitive receptors, continually evoke reflexes designed to maintain cardiovascular homeostasis. Although there is a growing body of knowledge regarding neural regulation of the adult cardiovascular system, characterization and understanding of these physiological systems during development is limited. This review highlights developmental changes in the arterial and cardiopulmonary baroreflex during fetal and postnatal life and contrasts the function of these responses with those seen in the adult. Baroreceptors are functional in the immature animal and reset toward higher pressure levels with maturation. In our ovine model, the sensitivity of the efferent limb of the baroreflex is greatest during fetal life and decreases with postnatal development. As in the adult, angiotensin II and arginine vasopressin interact with the sympathetic nervous system early during development to alter baroreflex control of the cardiovascular system. However, the extent to which these hormonal systems influence autonomic reflexes during the fetal and newborn period appears vastly different than in the adult. Endogenous angiotensin II significantly contributes to resetting of the arterial baroreflex early in life, whereas even high circulating levels of vasopressin have little effect on baroreflex function until adulthood. Finally, the ability of cardiopulmonary mechanoreceptors to regulate cardiovascular function is impaired early in development, in sharp contrast to the heightened sensitivity of the arterial baroreflex at this stage of maturation. The potential importance of these autonomic reflexes on cardiovascular function during the perinatal period is highlighted.
Febrile responsiveness of vagotomized rats is suppressed even in the absence of malnutrition
Authors: Romanovsky A. A. , Kulchitsky V. A. , Simons C. T. , Sugimoto N. , Szekely M.
Published: December 2017

The repeatedly observed attenuation of fever in vagotomized rats has been accepted as evidence of an essential role of vagal afferents in the transduction of pyrogenic signals from the periphery to the brain. If, however, the general condition of a vagotomized animal is poor (the usual case) and accompanied by malnutrition and body mass loss (common complications of vagotomy), the febrile responsiveness can be suppressed not because of the lack of vagal afferentation, but rather secondarily to a malnutrition-associated thermogenic incompetence. In the present study, we addressed this dilemma. Male Wistar rats were subjected to subdiaphragmatic vagotomy (or sham surgery) and, 24 days later, catheterized in the jugular vein. Postsurgically, the rats were closely watched and fed highly palatable food. Their febrile responsiveness [colonic (Tc) and tail skin (Tsk) temperature responses] to Escherichia coli lipopolysaccharide (LPS: 1 microgram/kg i.v.) was tested on day 27 postvagotomy. To verify the completeness of vagotomy, each rat was food deprived for 24 h and then euthanized; its stomach's evacuatory function was assessed by weighing the organ. One month postsurgery, both food consumption and body mass of the vagotomized rats (33 +/- 2 g/day and 313 +/- 4 g, respectively) were similar to the control values (30 +/- 1 g/day and 315 +/- 8 g). In the sham rats, LPS induced a monophasic Tc rise of 0.5 +/- 0.3 degree C at 70 min postinjection (peak), preceded by a fall in Tsk. Neither this Tsk fall (tail skin vasoconstriction) nor the resultant fever occurred in the vagotomized rats; at 70 min, Tc change was -0.1 +/-0.1 degree C. The gastric mass (4.1 +/- 0.5 g in the vagotomized vs. 1.8 +/- 0.1 g in sham rats) indicated the effectiveness of vagotomy. In sum, although the vagotomy-associated malnutrition was successfully prevented with special perioperative care, the vagotomized animals still did not respond to LPS with fever. Malnutrition is, therefore, unlikely to constitute the main reason of the febrile irresponsiveness of vagotomized rats.
NMDA receptor coagonist glycine site: evidence for a role in lateral hypothalamic stimulation of feeding
Authors: Stanley B. G. , Butterfield B. S. , Grewal R. S.
Published: December 2017

To investigate the role of the glycine coagonist binding site on the N-methyl-D-aspartate (NMDA) receptor in feeding control, we injected the glycine site antagonist 7-chlorokynurenic acid (7-CK) into the lateral hypothalamus (LH) of satiated rats before LH injection of NMDA, 7-CK (10-44 nmol) blocked the 6- to 10-g eating response elicited by NMDA. This block was reversed by LH pretreatment with glycine, arguing for a specific action at the glycine site. In contrast to the suppression produced by high doses, 7-CK at 0.1 nmol enhanced NMDA-elicited eating. For examination of behavioral specificity, 7-CK was injected into the LH before kainic acid (KA) or DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA). 7-CK at a dose of 0.1 nmol suppressed feeding elicited by KA or AMPA, but at 10 nmol it suppressed eating elicited by AMPA while enhancing eating elicited by KA. Finally, bilateral LH injection of 7-CK effectively suppressed eating produced by fasting. These findings support a role for the NMDA receptor coagonist glycine site in LH regulation of eating behavior.
Renal and amniotic fluid responses to umbilicoplacental embolization for 20 days in fetal sheep
Authors: Cock M. L. , Harding R.
Published: December 2017

We determined the effects of placental insufficiency induced by umbilicoplacental embolization on fetal renal function and amniotic fluid volume and composition. Pregnant ewes underwent surgery at 115 +/- 2 days after mating (term approximately 147 days) for implantation of fetal vascular, bladder, and amniotic sac catheters. We studied five fetuses from 120 to 140 days during umbilicoplacental embolization and six control fetuses. Umbilicoplacental embolization reduced fetal arterial partial pressure of oxygen from 24.1 +/- 0.5 mmHg (pretreatment) to 14.6 +/- 0.2 mmHg. Fetal body weights were reduced to 80% of control values. Urine production and glomerular filtration rate in treated fetuses were significantly lower than in controls at 135 days of gestation. Amniotic fluid volume was not different between embolized and control animals. Fetal urine production in treated fetuses, when adjusted for body weight, was not different from that in control fetuses. We conclude that, in fetal growth restriction, reduced kidney weight, rather than hypoxemia per se is responsible for reduced urine production, which, if severe and prolonged, may contribute to oligohydramnios.
Location and quantification of muscarinic receptor subtypes in rat pons: implications for REM sleep generation
Authors: Baghdoyan H. A.
Published: December 2017

Microinjecting cholinomimetics into the pontine reticular formation produces a state that resembles natural rapid eye movement (REM) sleep. Evocation of this REM sleeplike states is anatomically site dependent within the pons and is mediated by muscarinic receptors. The cellular and molecular mechanisms underlying cholinergic REM sleep generation and muscarinic receptor subtype involvement remain to be specified. This study tested the hypothesis that muscarinic receptor subtypes are differentially distributed within the oral and caudal divisions of rat pontine reticular nucleus. In vitro receptor autoradiography was used to localize and quantify M1, M2, and M3 binding sites in the pontine reticular formation and in pontine brain stem regions known to regulate REM sleep. M1-M3 binding sites were present in some REM sleep-related nuclei, such as dorsal raphe and locus ceruleus. The pontine reticular formation was found to have a homogeneous distribution of M2 binding sites across its rostral to caudal extent, indicating that anatomic specificity of cholinergic REM sleep induction cannot be accounted for by a differential density of muscarinic receptors.
Interleukin-6 is differently modulated by central opioid receptor subtypes
Authors: Bertolucci M. , Perego C. , De Simoni M. G.
Published: December 2017

The central endogenous opioid system is involved in the modulation of interleukin (IL)-6, an inflammatory cytokine that plays a major role in the acute phase response. The present study evaluates whether specific opioid receptor subtypes are selectively involved in this immunomodulatory action. IL-1 beta was administered either intracerebroventricularly or intraperitoneally at the dose of 400 ng to rats pretreated with the mu-antagonist beta-funaltrexamine, the delta-antagonist naltrindole, or the kappa-antagonist nor-binaltorphimine, each at the doses of 1, 10, and 100 micrograms/rat intracerebroventricularly. Serum IL-6 levels were measured 2 h later. The results show that mu-receptor blockade increases, whereas delta-receptor blockade decreases IL-6 induction, suggesting that the fine tuning exerted by opioids on the immune system may be achieved through a balance of opposing effects. Moreover the three antagonists affect IL-6 induction by central and peripheral IL-1 beta with a similar pattern, indicating that the brain endogenous opioid system plays a general role in the regulation of this cytokine.
Differential effects of dorsomedial medulla lesion size on ingestive behavior in rats
Authors: Wang Tianlun , Edwards Gaylen L.
Published: December 2017

Previous studies indicate that rats with lesions centered on the area postrema (AP) drink more saline and consume abnormally large amounts of water after treatment with subcutaneous isoproterenol (Iso) or angiotensin II. In addition, lesioned rats lose a significant amount of body weight immediately after surgery. Nonetheless, there are disparate reports on the effects of lesions of the AP on fluid intake and body weight. These reports suggest that the adjacent nucleus of the solitary tract (NTS) may play a role in the effects observed subsequent to the lesion. In this study we evaluated the effects of varying lesion size on body weight, fluid intake, and the baroreflex. As the lesion included more of the NTS, the effect on body weight was reduced. Moreover, water intake induced by Iso increased as more NTS was involved in the lesion. Conversely, 3-h ad libitum saline intake and saline intake after sodium depletion decreased with more involvement of the NTS in the lesion. These data suggest that the neural population in the NTS bordering the AP may play a critical role in the control of water and saline intake as well as the regulation of body weight.
Long-term effects of AVP-induced neurohumoral interaction via area postrema on body fluid and blood pressure
Authors: Nishida Yasuhiro , Hosomi Hiroshi , Bishop Vernon S.
Published: December 2017

Arginine vasopressin (AVP) has been known to interact with the central nervous system via the area postrema (AP), resulting in suppression of renal sympathetic outflow in short-term studies. We hypothesize that if this sympathoinhibitory effect lasts long, then the neurohumoral interaction would enhance urinary output because of the suppression of neurogenic reuptake of sodium (Na+) and water. Intact (Int) and AP-lesioned (APX) rabbits were chronically catheterized and housed in metabolic cages. AVP was intravenously infused (0.1 mU ⋅ kg−1 ⋅ min−1) for 5 consecutive days. Urine volume and urinary Na+excretion rates in Int rabbits were lower than those in APX rabbits during AVP infusion. This smaller urinary output in Int rabbits was reconfirmed either from the daily balance of water and Na+or from the body weight, plasma Na+ concentration, and plasma osmolality data. This result contradicted the hypothesis. Mean arterial pressure was not altered in either group of rabbits while heart rate was suppressed in the Int rabbits. These data suggest that AP-mediated long-term action of AVP augments water retention and sustains bradycardia.
Low urine flow reduces the capacity to excrete a sodium load in humans
Authors: Choukroun Gabriel , Schmitt François , Martinez Franck , Drüeke Tilman B. , Bankir Lise
Published: December 2017

Recent studies in rats suggest that vasopressin and the resulting urinary concentrating activity reduce the capacity of the kidney to excrete sodium. The present study investigates the influence of the level of hydration on the excretion of a sodium load in humans. Eight healthy male volunteers (18–35 yr) were studied twice, in random order, under either low (LowH) or high (HighH) hydration. They drank throughout the study either 0.25 (LowH) or 2.0 ml water/kg body wt (HighH) every 30 min. After 1 h equilibration, urine was collected for 2 h before (basal) and 10 h after the NaCl load (5 g NaCl in 250 ml, infused intravenously over 30 min). Differences in excretory patterns between LowH and HighH were mostly confined to the first 4 h after the load. The increase in Na excretion after the load was more intense under HighH than under LowH (+10.9 ± 2.6 vs. +5.8 ± 2.7 mmol/h in the first 4 postload h; P < 0.001). Under HighH, urine flow rate (V) increased markedly (+41%), with little change in urinary Na concentration (UNa), whereas under LowH, V declined slightly and UNa rose significantly (+33%). The capacity to raise UNa seemed to reach a maximum at ≈280 mM. In both conditions, the changes in UNa observed after the load were positively correlated with basal UNa. After the load, urea excretion increased under HighH and decreased under LowH, whereas K excretion was unaffected in either condition. These results show that sodium excretion is facilitated by an abundant water supply. The less efficient sodium excretion occurring at low V is probably due to the influence of vasopressin on water, urea, and sodium movements across the collecting ducts. These observations suggest that, in everyday life, a low water intake could limit the capacity to excrete sodium. Whether this could contribute to salt-sensitive hypertension remains to be evaluated.
Medullary inputs to nucleus accumbens neurons
Authors: Kirouac Gilbert J. , Ciriello John
Published: December 2017

Extracellular single-unit recording experiments were done in α-chloralose-anesthetized, paralyzed, and artificially ventilated rats to investigate the effect of stimulation of the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) in the region of the A1 noradrenergic cell group on the activity of neurons in the nucleus accumbens (NA). In addition, the response of NA neurons to activation of the arterial baroreceptors was investigated. Electrical or glutamate (Glu) stimulation of the ipsilateral NTS excited 47 of 99 (48%) and inhibited 10 of 99 (10%) of the units tested in the NA. Similarly, electrical or Glu stimulation of the ipsilateral VLM excited 24 of 97 (24.7%) or inhibited 7 of 97 (7.2%) of the units tested. Approximately 22% (17 of 77) of these units responded to stimulation of both the NTS and VLM. Simultaneous stimulation of both the NTS and VLM potentiated the response of the NA neuron tested. CoCl2 injection into the ipsilateral NTS did not alter the response of NA neurons to stimulation of the VLM. Similarly, CoCl2 injections into the ipsilateral VLM did not alter the response of NA neurons to NTS stimulation. The discharge rate of some of the units (6 of 49) that were activated by both NTS and VLM was also increased during the activation of arterial baroreceptors by the acute rise in systemic arterial pressure to phenylephrine injection. Units that responded to stimulation of the NTS and VLM and to baroreceptor activation were located in the shell region of the NA. These data indicate that afferent inputs from the NTS and VLM converge onto NA neurons and suggest that visceral and cardiovascular afferent inputs may influence the output of neurons in the shell region of the NA.
Defense of differfing body weight set points in diet-induced obese and resistant rats
Authors: Levin Barry E. , Keesey Richard E.
Published: December 2017

Among outbred Sprague-Dawley rats, approximately one-half develop diet-induced obesity (DIO) and one-half are diet resistant (DR) on a diet relatively high in fat and energy content (HE diet). Here we examined the defense of body weight in these two phenotypes. After HE diet for 13 wk, followed by chow for 6 wk, DR rats gained weight comparably but their plasma leptin levels fell to 54% of chow-fed controls. When a palatable liquid diet (Ensure) was added for 13 wk, other DR rats became obese. But when switched to chow, their intakes fell by 60%, and body and retroperitoneal (RP) fat pad weights and plasma leptin and insulin levels all declined for 2 wk and then stabilized at control levels after 6 wk. In contrast, comparably obese DIO rats decreased their intake by only 20%, and their weights plateaued when they were switched to chow after 13 wk on HE diet. When a subgroup of these DIO rats was restricted to 60% of prior intake, their weights fell to chow-fed control levels over 2 wk. But their leptin and insulin levels both fell disproportionately to 30% of controls. When no longer restricted, their intake and feed efficiency rose immediately, and their body and RP pad weights and leptin and insulin levels rose to those of unrestricted DIO rats within 2 wk. Thus diet and genetic background interact to establish high (DIO) or low (DR) body weight set points, which are then defended against subsequent changes in diet composition and/or energy availability. If leptin affects energy homeostasis, it does so differentially in DIO vs. DR rats since comparably low and high levels were associated with differing patterns of weight change between the two phenotypes.
Inward rectifier potassium channels in the rat middle cerebral artery
Authors: Johnson T. David , Marrelli Sean P. , Steenberg Marie L. , Childres William F. , Bryan Robert M.
Published: December 2017

Inward rectifier K+ channels (Kirs) were studied in the isolated perfused rat middle cerebral artery (MCA). The addition of 15 mM K+ (KCl) to the extraluminal bath dilated the MCAs. These dilations were blocked by selective inhibitors for the Kirs (40 μM BaCl2 or 40 mM CsCl) but not selective inhibitors for other K+channels (glibenclamide, tetraethylammonium, or 4-aminopyridine). Neither removal of the endothelium nor treatment with the nitric oxide synthase inhibitor ( N G-nitro-l-arginine methyl ester, 10 μM) affected the K+-induced dilation. The addition of BaCl2 to resting MCAs produced a dose-dependent constriction of 8–12%, indicating that, during resting conditions, Kirs aid in setting or determining the resting tone. The magnitude of the dilations produced by the addition of K+ or constrictions produced by BaCl2 were independent of pressure over a range of 40–100 mmHg. We conclude that Kirs, which produce a dilation when activated, exist on the vascular smooth muscle of the rat MCA. These Kirs aid in determining the resting tone of the vessel, and their function is independent of pressure over physiological pressure ranges.
Altered frequency characteristics of sympathetic nerve activity after sustained elevation in arterial pressure
Authors: Claassen Dale E. , Fels Richard J. , Kenney Michael J.
Published: December 2017

We tested the hypothesis that sustained elevation in mean arterial pressure (MAP) alters the frequency-domain characteristics of efferent sympathetic nerve discharge (SND) after the return of MAP to control levels. Renal, lumbar, and splanchnic SND were recorded before, during, and after a 30-min increase in MAP produced by phenylephrine (PE) infusion in α-chloralose-anesthetized, spontaneously hypertensive (SH) rats. The following observations were made. 1) The basic cardiac-locked pattern of renal, lumbar, and splanchnic SND bursts was altered after sustained elevation in MAP, demonstrating prolonged effects on the neural circuits involved in entraining efferent SND to the cardiac cycle. Importantly, discharge bursts in afferent baroreceptor nerve activity remained pulse-synchronous after sustained increases in arterial pressure. 2) The frequency-domain relationships between the activity in sympathetic nerve pairs were altered after sustained elevation in MAP, suggesting a transformation from a system of tightly coupled neural circuits to one of multiple generators exerting selective control over SND. 3) The most prominent reduction in SND power after sustained elevation in MAP occurred in the frequency band containing the cardiac cycle, indicating that the prolonged suppression of SND after sustained increases in arterial pressure is due primarily to the selective inhibition of cardiac-related SND bursts. We conclude that sustained elevation in MAP profoundly affects the neural circuits responsible for the frequency components of basal SND in SH rats.
Microinjection of a cyclooxygenase inhibitor into the anteroventral preoptic region attenuates LPS fever
Authors: Scammell Thomas E. , Griffin John D. , Elmquist Joel K. , Saper Clifford B.
Published: December 2017

Considerable evidence supports the role of prostaglandins in fever production, but the neuroanatomic sites of prostaglandin synthesis that produce fever remain unknown. With the use of a novel microinjection technique, we injected the cyclooxygenase inhibitor ketorolac into the preoptic area (POA) to determine which preoptic regions produce the prostaglandins required for fever. Initial experiments demonstrated that intravenous ketorolac blocked the fever normally produced by lipopolysaccharide (LPS) 5 μg/kg iv. Microinjection of ketorolac into the POA had no effect on body temperature, and injection of artificial cerebrospinal fluid into the POA did not alter LPS fever. Injection of ketorolac into the anteroventral POA markedly decreased the fever produced by LPS, compared with injections into more rostral, caudal, or dorsal locations. These observations indicate that prostaglandin synthesis in the anteroventral preoptic region is necessary for the production of fever.
Photic resetting of intrinsic rhythmicity of the rat suprachiasmatic nucleus under various photoperiods
Authors: Sumová Alena , Illnerová Helena
Published: December 2017

To date, photic entrainment of the mammalian circadian system has been studied by following phase shifts of overt rhythms in the periphery governed by a circadian pacemaker located in the suprachiasmatic nucleus (SCN). The present study follows for the first time photic resetting of intrinsic rhythmicity of the SCN itself. Rats maintained under either a shorter photoperiod, with 12 h of light and 12 h of darkness per day, or under a long, 18:6-h light-dark photoperiod were exposed to a light stimulus during the dark period and then released into darkness, and the next day the SCN rhythm in the light-stimulated c-Fos protein immunoreactivity was followed as a marker of the SCN endogenous rhythmicity. After a light stimulus in the early night, the evening rise in the photic elevation of Fos protein photoinduction as well as the morning decline were phase delayed within one cycle. After a light stimulus in the late night, only the morning decline in the photic elevation of Fos was phase advanced the next night, not the evening rise; consequently, the interval enabling high photic elevation of Fos was reduced. After a light stimulus was administered around the middle of the night, the next night the evening rise in the light-stimulated Fos was eventually phase delayed, the morning decline was phase advanced, and the rhythm amplitude was reduced significantly; under 18:6-h light-dark, a mere 5-min light exposure exhibited such effects. The data indicate that resetting of the SCN rhythmicity in the light-elevated c-Fos 1 day after a resetting stimulus administration, i.e., during transient cycles, may proceed via nonparallel phase shifts of the evening rise and of the morning decline of the light-stimulated Fos, and via amplitude lowering and suggest a complex circadian pacemaking system in the rat SCN.
Nitric oxide is the predominant mediator of cerebellar hyperemia during somatosensory activation in rats
Authors: Yang Guang , Chen Gang , Ebner Timothy J. , Iadecola Costantino
Published: December 2017

Crus II is an area of the cerebellar cortex that receives trigeminal afferents from the perioral region. We investigated the mechanisms of functional hyperemia in cerebellum using activation of crus II by somatosensory stimuli as a model. In particular, we sought to determine whether stimulation of the perioral region increases cerebellar blood flow (BFcrb) in crus II and, if so, whether the response depends on activation of 2-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-kainate receptors and nitric oxide (NO) production. Crus II was exposed in anesthetized rats, and the site was superfused with Ringer. Field potentials were recorded, and BFcrb was measured by laser-Doppler flowmetry. Crus II was activated by electrical stimulation of the perioral region (upper lip). Perioral stimulation evoked the characteristic field potentials in crus II and increased BFcrb (34 ± 6%; 10 Hz-25 V; n = 6) without changing arterial pressure. The BFcrb increases were associated with a local increase in glucose utilization (74 ± 8%; P < 0.05; n = 5) and were attenuated by the AMPA-kainate receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-[f]quinoxaline (−71 ± 3%; 100 μM; P < 0.01; n = 5). The neuronal NO synthase inhibitor 7-nitroindazole (7-NI, 50 mg/kg; n = 5) virtually abolished the increases in BFcrb(−90 ± 2%; P < 0.01) but did not affect the amplitude of the field potentials. In contrast, 7-NI attenuated the increase in neocortical cerebral blood flow produced by perioral stimulation by 52 ± 6% ( P < 0.05; n = 5). We conclude that crus II activation by somatosensory stimuli produces localized increases in local neural activity and BFcrbthat are mediated by activation of glutamate receptors and NO. Unlike in neocortex, in cerebellum the vasodilation depends almost exclusively on NO. The findings underscore the unique role of NO in the mechanisms of synaptic function and blood flow regulation in cerebellum.
Reduction of food intake by intestinal macronutrient infusion is not reversed by NMDA receptor blockade
Authors: Covasa M. , Ritter R. C. , Burns G. A.
Published: December 2017

Rats increase their intake of food, but not water, after intraperitoneal injection of MK-801, a noncompetitive antagonist of N-methyl-d-aspartate-activated ion channels. We hypothesized that MK-801 might enhance intake by interfering with intestinal chemosensory signals. To test this hypothesis, we examined the effect of the antagonist on 15% sucrose intake after an intraduodenal infusion of maltotriose, oleic acid, or phenylalanine in both real- and sham-feeding paradigms. MK-801 (100 μg/kg) significantly increased sucrose intake regardless of the composition of the infusate during real feeding. Furthermore, MK-801 had no effect on reduction of sucrose intake by intestinal nutrient infusions in sham-feeding rats. These results indicate that MK-801 does not increase meal size and duration by interfering with signals activated by intestinal macronutrients.
Baroreflex control of muscle sympathetic nerve activity after 120 days of 6° head-down bed rest
Authors: Kamiya Atsunori , Iwase Satoshi , Kitazawa Hiroki , Mano Tadaaki , Vinogradova Olga L. , Kharchenko Irina B.
Published: December 2017

To examine how long-lasting microgravity simulated by 6° head-down bed rest (HDBR) induces changes in the baroreflex control of muscle sympathetic nerve activity (MSNA) at rest and changes in responses of MSNA to orthostasis, six healthy male volunteers (range 26–42 yr) participated in Valsalva maneuver and head-up tilt (HUT) tests before and after 120 days of HDBR. MSNA was measured directly using a microneurographic technique. After long-term HDBR, resting supine MSNA and heart rate were augmented. The baroreflex slopes for MSNA during Valsalva maneuver (in supine position) and during 60° HUT test, determined by least-squares linear regression analysis, were significantly steeper after than before HDBR, whereas the baroreflex slopes for R-R interval were significantly flatter after HDBR. The increase in MSNA from supine to 60° HUT was not different between before and after HDBR, but mean blood pressure decreased in 60° HUT after HDBR. In conclusion, the baroreflex control of MSNA was augmented, whereas the same reflex control of R-R interval was attenuated after 120 days of HDBR.
Vasopressin and oxytocin release evoked by NaCl loads are selectively blunted by area postrema lesions
Authors: Huang Wan , Sved Alan F. , Stricker Edward M.
Published: December 2017

The present study investigated the effect of area postrema lesions (APX) on stimulated neurohypophysial secretion of vasopressin (VP) and oxytocin (OT) in conscious rats. Blunted increases in plasma levels of both pituitary hormones were observed when rats with APX were infused intravenously with 1 M NaCl solution (2 ml/h for 6 h). In contrast, plasma VP and OT increased normally in rats with APX when equivalent increases in plasma osmolality (but not plasma Na+) resulted from intravenous infusion of an equiosmotic solution of 1 M mannitol and 0.5 M NaCl. Furthermore, APX did not affect increases in plasma VP and OT stimulated by plasma volume deficits, nor did APX disrupt OT secretion stimulated by intravenous injection of cholecystokinin. These findings suggest that the area postrema plays an important role in mediating secretion of VP and OT in response to an NaCl load, but not in response to an equiosmotic load that does not cause substantial hypernatremia, and not in response to other stimuli of neurohypophysial hormone secretion. Together with previous reports, these results suggest that APX impairs Na+ regulation in rats.
Rhythmic multiunit neural activity in slices of hamster suprachiasmatic nucleus reflect prior photoperiod
Authors: Mrugala Maciej , Zlomanczuk Piotr , Jagota Anita , Schwartz William J.
Published: December 2017

The suprachiasmatic nucleus (SCN) is an endogenous circadian pacemaker, and SCN neurons exhibit circadian rhythms of electrophysiological activity in vitro. In vivo, the functional state of the pacemaker depends on changes in day length (photoperiod), but it is not known if this property persists in SCN tissue isolated in vitro. To address this issue, we prepared brain slices from hamsters previously entrained to light-dark (LD) cycles of different photoperiods and analyzed rhythms of SCN multiunit neuronal activity using single electrodes. Rhythms in SCN slices from hamsters entrained to 8:16-, 12:12-, and 14:10-h LD cycles were characterized by peak discharge rates relatively higher during subjective day than subjective night. The mean duration of high neuronal activity was photoperiod dependent, compressed in slices from the short (8:16 and 12:12 LD) photoperiods, and decompressed (approximately doubled) in slices from the long (14:10 LD) photoperiod. In slices from all photoperiods, the mean phase of onset of high neuronal activity appeared to be anchored to subjective dawn. Our results show that the electrophysiological activity of the SCN pacemaker depends on day length, extending previous in vivo data, and demonstrate that this capacity is sustained in vitro.
Medullary lateral tegmental field: an important source of basal sympathetic nerve discharge in the cat
Authors: Barman Susan M. , Gebber Gerard L. , Orer Hakan S.
Published: December 2017

We used blockade of excitatory amino acid (EAA) neurotransmission in the medullary lateral tegmental field (LTF) and rostral ventrolateral medulla (RVLM) to assess the roles of these regions in the control of inferior cardiac sympathetic nerve discharge (SND) and mean arterial pressure (MAP) in urethan-anesthetized, baroreceptor-denervated cats. Bilateral microinjection of a non- N-methyl-d-aspartate (NMDA)-receptor antagonist [1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo-[f]quinoxaline-7-sulfonamide (NBQX)] into the LTF significantly decreased SND to 46 ± 4% of control (as demonstrated with power-density spectral analysis) and MAP by 16 ± 6 mmHg. In contrast, bilateral microinjection of an NMDA-receptor antagonist [d(−)-2-amino-5-phosphonopentanoic acid (d-AP5)] into the LTF did not decrease SND or MAP. These results demonstrate that the LTF is an important synaptic relay in the pathway responsible for basal SND in the cat. Bilateral microinjection of NBQX or d-AP5 into the RVLM significantly decreased power in SND to 48 ± 5 or 61 ± 5% of control, respectively, and reduced MAP by 15 ± 2 or 8 ± 4 mmHg, respectively. These data indicate that EAA-mediated synaptic drive to RVLM-spinal sympathoexcitatory neurons accounts for a significant component of their basal activity.
GABAB presynaptically modulates suprachiasmatic input to hypothalamic paraventricular magnocellular neurons
Authors: Cui Lu-Ning , Coderre Elaine , Renaud Leo P.
Published: December 2017

This study used whole cell patch clamp recordings in rat hypothalamic slice preparations to evaluate the effects of GABAB receptor activation on GABAA-mediated inhibitory postsynaptic currents (IPSCs) in paraventricular nucleus magnocellular neurons evoked by electrical stimulation in the suprachiasmatic nucleus (SCN). Baclofen induced a dose-dependent (1–10 μM) and reversible reduction in SCN-evoked IPSC amplitude (11/11 cells), blockable with 2-hydroxysaclofen (300 μM; 3/3 cells). IPSCs displayed paired-pulse depression (PPD), attenuated by both baclofen and 2-hydroxysaclofen, but neither altered resting membrane conductances or IPSC time constants of decay. Baclofen induced a significant dose-dependent (1–100 μM) reduction in frequency, but not amplitude, of spontaneous IPSCs and miniature IPSCs, reversible with 2-hydroxysaclofen pretreatment. Baclofen effects and PPD persisted in slices pretreated with pertussis toxin (PTX) and N-ethylmaleimide, implying that these GABABreceptors are coupled to PTX-insensitive G proteins. Responses were unaltered by barium (2 mM) or nimodipine, ruling out involvement of K+ channels and L-type Ca2+ channels. Thus pre- and postsynaptic GABAB and GABAA receptors participate in SCN entrainment of paraventricular neurosecretory neurons.
Effects of midbrain and spinal cord transections on sympathetic nerve responses to heating
Authors: Kenney Michael J. , Pickar Joel G. , Weiss Mark L. , Saindon Cristina S. , Fels Richard J.
Published: December 2017

In the present study, we investigated the contributions of forebrain, brain stem, and spinal neural circuits to heating-induced sympathetic nerve discharge (SND) responses in chloralose-anesthetized rats. Frequency characteristics of renal and splenic SND bursts and the level of activity in these nerves were determined in midbrain-transected (superior colliculus), spinal cord-transected [first cervical vertebra (C1)], and sham-transected (midbrain and spinal cord) rats during progressive increases in colonic temperature (Tc) from 38 to 41.6–41.7°C. The following observations were made. 1) Significant increases in renal and splenic SND were observed during hyperthermia in midbrain-transected, sham midbrain-transected, C1-transected, and sham C1-transected rats. 2) Heating changed the discharge pattern of renal and splenic SND bursts and was associated with prominent coupling between renal-splenic discharge bursts in midbrain-transected, sham midbrain-transected, and sham C1-transected rats. 3) The pattern of renal and splenic SND bursts remained unchanged from posttransection recovery levels during heating in C1-transected rats. We conclude that an intact forebrain is not required for the full expression of SND responses to increased Tc and that spinal neural systems, in the absence of supraspinal circuits, are unable to markedly alter the frequency characteristics of SND in response to acute heat stress.
Anatomic patterning in the expression of vestibulosympathetic reflexes
Authors: Kerman I. A. , Yates B. J. , McAllen R. M.
Published: December 2017

To investigate the possibility that expression of vestibulosympathetic reflexes (VSR) is related to a nerve's anatomic location rather than its target organ, we compared VSR recorded from the same type of postganglionic fiber [muscle vasoconstrictor (MVC)] located at three different rostrocaudal levels: hindlimb, forelimb, and face. Experiments were performed on chloralose-anesthetized cats, and vestibular afferents were stimulated electrically. Single MVC unit activity was extracted by spike shape analysis of few-fiber recordings, and unit discrimination was confirmed by autocorrelation. Poststimulus time histogram analysis revealed that about half of the neurons were initially inhibited by vestibular stimulation (type 1 response), whereas the other MVC fibers were initially strongly excited (type 2 response). MVC units with types 1 and 2 responses were present in the same nerve fascicle. Barosensitivity was equivalent in the two groups, but fibers showing type 1 responses fired significantly faster than those giving type 2 responses (0.29 ± 0.04 vs. 0.20 ± 0.02 Hz). Nerve fibers with type 1 responses were most common in the hindlimb (21 of 29 units) and least common in the face (2 of 11 units), the difference in relative proportion being significant ( P < 0.05, χ2 test). These results support the hypothesis that VSR are anatomically patterned.
Effects of photoperiod reduction on rat circadian rhythms of BP, heart rate, and locomotor activity
Authors: Zhang Bei-Li , Zannou Erika , Sannajust Frédéric
Published: December 2017

The effects of a photoperiod reduction in the entrainment of circadian rhythms of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and spontaneous locomotor activity (SLA) were determined in conscious Wistar rats by using radiotelemetry. Two groups of seven rats were maintained in a 12:12-h light-dark (12L/12D) photoperiod for 11 wk and then placed in a reduced photoperiod of 8:16-h light-dark (8L/16D) by advancing a 4-h darkness or by advancing and delaying a 2-h darkness for 6 wk. Finally, they were resynchronized to 12L/12D. Advancing a 4-h dark phase induced a 1-h advance of acrophase for SBP, DBP, and HR, but not for SLA. The percent rhythm, amplitude, and the 12-h mean values of all parameters were significantly decreased by the photoperiod reduction. When symmetrically advancing and delaying a 2-h dark phase, a 1 h 20 min delay of acrophases and a decrease in percent rhythms and amplitudes of SBP, DBP, HR, and SLA were observed. Only the 12-h mean values of HR and SLA were decreased. Our findings show that the cardiovascular parameters differ from SLA in phase-shift response to photoperiod reduction and that the adjustment of circadian rhythms to change from 12L/12D to 8L/16D photoperiod depends on the direction of the extension of the dark period.
Spinal GABAA receptors do not mediate the sympathetic baroreceptor reflex in the rat
Authors: Goodchild Ann K. , Van Deurzen Bart T. M. , Sun Qi-Jian , Chalmers John , Pilowsky Paul M.
Published: December 2017

Activation of baroreceptors causes efferent sympathetic nerve activity (SNA) to fall. Two mechanisms could account for this sympathoinhibition: disfacilitation of sympathetic preganglionic neurons (SPN) and/or direct inhibition of SPN. The roles that spinal GABA and glycine receptors play in the baroreceptor reflex were examined in anesthetized, paralyzed, and artificially ventilated rats. Spinal GABAA receptors were blocked by an intrathecal injection of bicuculline methiodide, whereas glycine receptors were blocked with strychnine. Baroreceptors were activated by stimulation of the aortic depressor nerve (ADN), and a somatosympathetic reflex was used as control. After an intrathecal injection of vehicle, there was no effect on any measured variable or evoked reflex. In contrast, bicuculline caused a dose-dependent increase in arterial pressure, SNA, phrenic nerve discharge, and it significantly facilitated the somatosympathetic reflex. However, bicuculline did not attenuate either the depressor response or sympathoinhibition evoked after ADN stimulation. Similarly, strychnine did not affect the baroreceptor-induced depressor response. Thus GABAA and glycine receptors in the spinal cord have no significant role in baroreceptor-mediated sympathoinhibition.
An oral platelet-activating factor antagonist, Ro-24-4736, protects the rat kidney from ischemic injury
Authors: Kelly K. J. , Tolkoff-Rubin N. E. , Rubin R. H. , Williams W. W. , Meehan S. M. , Meschter C. L. , Christenson J. G. , Bonventre J. V.
Published: December 2017

The role of platelet-activating factor (PAF) in ischemic acute renal failure was evaluated by administering an oral PAF antagonist (Ro-24-4736) to rats prior to or after interruption of blood flow to both kidneys for 30 min. In animals treated with the PAF antagonist prior to ischemia, renal function was less impaired and histological abnormalities was less pronounced when compared with postischemic kidneys from vehicle-treated animals. Serum creatinine (mg/ dl) 24 h following renal ischemia was 1.58 +/- 0.17 in the PAF antagonist-treated rats compared with 2.19 +/- 0.15 in rats given placebo (P < 0.01). There was less necrosis in the outer medulla of kidneys of PAF antagonist-treated animals (P < 0.01). Tissue myeloperoxidase activity at 48 and 72 h postischemia was lower in kidneys of PAF antagonist-treated rats (P < 0.05). The PAF antagonist was also protective when administered 30 min but not 2 h following the ischemic insult. The coincident use of anti-intercellular adhesion molecule-1 monoclonal antibody did not confer additional protection over that observed with the oral PAF antagonist alone. These data suggest that PAF contributes to the pathophysiology of renal ischemic injury, perhaps by its effects on leukocyte-endothelial interactions. An orally active PAF antagonist can protect against the development of ischemic acute renal failure.
The molecular basis of inherited hypokalemic alkalosis: Bartter's and Gitelman's syndromes
Authors: Simon D. B. , Lifton R. P.
Published: December 2017

Hypokalemic alkalosis with low blood pressure can be caused by a number of medications or alternatively as an autosomal recessive genetic trait. Molecular genetic approaches to this problem have recently demonstrated that mutations in genes encoding the thiazide-sensitive Na-Cl cotransporter or the bumetanide-sensitive Na-K-2Cl cotransporter produce two distinctive clinical and physiological pictures featuring hypokalemic alkalosis. Mutations in the latter cause a phenotypic picture called Bartter's syndrome that includes marked hypercalciuria and neonatal presentation with marked intravascular volume depletion. Mutations in the former cotransporter result in Gitelman's syndrome, which includes hypocalciuria, hypomagnesemia, and typically older clinical presentation with predominant muscular signs and symptoms. These findings establish the molecular basis of these disorders and indicate that the diverse abnormalities seen in affected patients derive from primary defects in these mediators of cotransport function. Moreover, these findings have implications for normal mechanisms of renal electrolyte homeostasis and for potential phenotypic effects in the more common heterozygous carriers of these mutations.
Inhibition of carbonic anhydrase: its effect on carbon dioxide elimination by the lungs
Authors: Mithoefer John C.
Published: December 2017

The effect of carbonic anhydrase inhibition on carbon dioxide elimination by the lungs has been studied in dogs by the following four experimental approaches: 1) the alveolar pathway (PaOO2 and PaCOCO2) was measured during the hyperventilation which follows carbonic anhydrase inhibition and compared to the normal pathway at the same hyperventilation. 2) The alveolar gas tensions were measured following carbonic anhydrase inhibition when the ventilation was held constant. 3) The changes in PaCOCO2 were measured when the ventilation was suddenly, artificially changed to a new level in the presence of carbonic anhydrase inhibition and in normal animals. 4) The CO2 output was measured directly during the hyperventilation which results from carbonic anhydrase inhibition, during the same hyperventilation in the normal animal and following carbonic anhydrase inhibition when the ventilation is held constant. These experiments demonstrate an immediate fall in CO2 output relative to the ventilation when carbonic anhydrase is inhibited, resulting in CO2 retention until a new steady state has been reached. An hypothesis is presented to explain the effect of carbonic anhydrase inhibition on CO2 transport.

Submitted on March 28, 1958
Interpretation of urinary N15-excretion data following administration of an N15-labeled amino acid
Authors: Wu Hsien , Sendroy Julius , Bishop Charles W.
Published: December 2017

A discussion is given of the problems encountered in the interpretation of urinary excretion data when the isotope concentration versus time curve is fitted to an exponential equation. The possibility of evaluating the size of the initial pool of the specific amino acid which is administered in labeled form, and its rate of turnover, is illustrated with ammonia excretion data from intravenous glycine experiments. The calculation of the size of other pools is shown with ammonia, hippuric acid and urea excretion data from oral glycine and phenylalanine experiments. From the cumulative total-N15 and urea-N15 excretion data in the later ‘post-equilibrium’ period, the rate of (apparently irreversible) protein synthesis has been calculated. The values (about 1 mEq/hr/kg body weight) obtained in intravenous and oral experiments on man with phenylalanine, glycine, aspartic acid and ammonium citrate are substantially the same. As the labeled-NH2 is incorporated into more and more compounds and as each of these labeled compounds diffuses into an increasing number of compartments of the body, the apparent size of the mixed amino-N pool, as reflected in the isotope concentration of a urinary compound such as ammonia, seems to expand with time until eventually it equals the total exchangeable-NH2 in the body.

Submitted on September 15, 1958
Suppression of sweet sensitivity by potassium gymnemate
Authors: Warren Richard M. , Pfaffmann Carl
Published: December 2017

The leaves of Gymnema sylvestre, when chewed, temporarily depress sensitivity to sweet and bitter substances. The active principle, potassium gymnemate, was isolated and shown to have quantitatively equal effects on the sweet taste of threshold and suprathreshold concentrations of sucrose and sodium saccharin. The possible mechanisms of action are discussed.

Submitted on December 10, 1956
Effects of restraint on oxygen consumption of the cold exposed guinea pig
Authors: Bartlett R. G.
Published: December 2017

The oxygen consumption of cold exposed, restrained guinea pigs is significantly greater than that of cold exposed, nonrestrained controls. Similar observations have been made for the rat ( Canad. J. Biochem. & Physiol. 33:654, 1955). These data strongly suggest that heat production is greater in the restrained animal than in the nonrestrained control. The hypothermia, then, accompanying restraint in the cold cannot be laid to a decreased muscular activity (muscular activity is actually increased) and a consequently lessened heat production, as suggested by some ( J. Appl. Physiol. 12:214, 1958). It must be due, as demonstrated for the rat ( Am. J. Physiol. 193:557, 1958), to an increased rate of heat loss. The marked physiological changes accompanying restraint should serve as a warning to the investigator who uses restraint for convenience in data collection.

Submitted on July 11, 1958