bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress-induced norepinephrine release in the rat prefrontal cortex measured by microdialysis
Authors: Nakane H. , Shimizu N. , Hori T.
Published: December 2017

Norepinephrine (NE) release in the medial prefrontal cortex (PFC) of rats was studied during immobilization using an intracerebral microdialysis technique. A series of experiments using pharmacological and physiological manipulations indicated that the NE recovered in the medial PFC dialysate was mainly derived from nerve terminals and that the dorsal noradrenergic bundle was a major source of NE in the medial PFC. Immobilization stress immediately elevated NE levels to 176.0 +/- 9.0% of basal release, and this increase continued for the entire period of stress and 20 min after termination of the stress. Preinjection of a benzodiazepine receptor agonist, diazepam (5 mg/kg ip), significantly attenuated immobilization-induced NE release, while injection of an anxiogenic compound, FG-7142 (20 mg/kg ip), facilitated NE release in an obviously nonstressed condition. These results therefore suggest that stressful stimuli activate the NE system in the medial PFC, which may be modulated by an activation of benzodiazepine receptors in the brain.
Validation of the doubly labeled water method in growing pigs
Authors: Haggarty P. , Franklin M. F. , Fuller M. F. , McGaw B. A. , Milne E. , Duncan G. , Christie S. L. , Smith J. S.
Published: December 2017

The CO2 production (rCO2) of eight growing pigs was determined by continuous collection of CO2 over 21 days and simultaneously estimated using the doubly labeled water (DLW) method. The aim was to assess the accuracy of the method before and after correction for known sources of error and to test for any residual discrepancy arising from as yet unidentified sources of error. Mass spectrometer accuracy was verified by analyzing serial dilutions of the dose material in the form of an artificial decay curve; no significant bias was detected. The physiological errors were linearly dependent on weight gain. DLW-derived rCO2 (corrected only for fractionated water loss) underestimated the true value by 0.270 l CO2/g wt gain or -8% in the restricted (group R) and -16% in the ad libitum-fed (group AL) groups. Known sources of error accounted for -0.006 (methane), -0.032 (fecal 2H losses), -0.108 (fat synthesis), and -0.146 (changing pool size) l CO2/g wt gain. After correction for these sources of error the DLW-derived rCO2 differed from the true value by -2 +/- 3% in group R and 0 +/- 3% in group AL. Thus there was no significant bias in the DLW method after correction for known sources of error, even during rapid weight gain or at weight stability with or without correction. The precision estimates include both dose and background errors and uncertainty in the correction factors used. Strategies for optimizing precision are presented.
Pregnant rats are refractory to the natriuretic actions of atrial natriuretic peptide
Authors: Masilamani S. , Castro L. , Baylis C.
Published: December 2017

Normal pregnant women and rats undergo a volume expansion. Atrial natriuretic peptide (ANP) is involved in volume homeostasis and is stimulated in response to volume expansion in nonpregnant animals, resulting in natriuresis and diuresis. The conscious, chronically catheterized rat was used to measure mean arterial blood pressure (MABP) and renal responses to administered ANP (160 ng.kg-1.min-1 i.v.) to determine if the actions of ANP are altered by pregnancy. These experiments examined virgin (n = 7) and pregnant rats, studied on gestational days 7-9 (n = 9) and 15-17 (n = 7). Renal clearance studies (with inulin and p-aminohippurate) were conducted in control conditions and during 60 min of ANP infusion. After the ANP infusion, plasma ANP concentrations were measured in virgin and pregnant rats. MABP fell with ANP infusion to similar absolute values in virgins (112 +/- 2 to 80 +/- 6 mmHg), 7- to 9-day pregnant (114 +/- 2 to 91 +/- 3 mmHg), and 15- to 17-day pregnant (107 +/- 2 to 88 +/- 4 mmHg) rats although the percent decline in MABP in 15- to 17-day pregnant rats was less than in virgins. Plasma ANP concentrations were similar in all groups. ANP had no effect on glomerular filtration rate, renal plasma flow, or renal vascular resistance in virgin or pregnant rats. ANP increased sodium excretion in virgins and in 7- to 9-day pregnant rats (+102 +/- 27 and +135 +/- 47%, respectively) but not in 15- to 17-day pregnant animals (+23 +/- 22%).(ABSTRACT TRUNCATED AT 250 WORDS)
Dissociation between vasopressin and oxytocin mRNA and peptide secretion after AV3V lesions
Authors: Morris M. , Rocha M. J. , Sim L. J. , Johnson A. K. , Callahan M. F.
Published: December 2017

The effect of hypertonic NaCl consumption on vasopressin (VP) and oxytocin (OT) mRNA levels and plasma and pituitary peptides was evaluated in rats with sham or anterior ventral third ventricular (AV3V) lesions. Rats were given tap water or 2% NaCl for 4 days. Because the rats with lesions drank significantly less salt solution than the controls (78.8 +/- 17.4 vs. 205.5 +/- 37.8 ml/4 days), a second control group was included in which saline intake was matched to the lesioned group. AV3V rats showed a deficit in the peptide response to the osmotic stimulus. There was no increase in plasma VP or OT or decrease in posterior pituitary peptide content in the face of an extreme hypernatremia: plasma sodium of 180.1 +/- 4.2 meq/l. Evaluation of mRNA changes by means of in situ hybridization showed that animals with lesions responded to the salt challenge with increases in hypothalamic VP and OT mRNA levels. There were significant increases in paraventricular and supraoptic OT mRNA and paraventricular VP mRNA in the lesioned group. The salt-matched control group showed no changes in peptide mRNA levels. These results demonstrate that AV3V lesions produce an impairment of the salt-neuroendocrine reflex but a persistence of the peptide mRNA response. Differences in control mechanisms must account for this dissociation between peptide mRNA expression and peptide secretion.
CNP is present in canine renal tubular cells and secreted by cultured opossum kidney cells
Authors: Nir A. , Beers K. W. , Clavell A. L. , Wei C. M. , Heublein D. M. , Dousa T. P. , Burnett J. C.
Published: December 2017

C-type natriuretic peptide (CNP) is a vasoactive and antimitogenic peptide that is structurally similar but genetically distinct from atrial natriuretic peptide. While first discovered in the brain, CNP has been shown to be produced by endothelial cells and may function in a paracrine and autocrine fashion in the control of vascular tone. Recently, CNP immunoreactivity and B-type natriuretic peptide receptors (NPR-B), for which CNP is a specific ligand, have been identified in the kidney. The present study was designed to determine whether renal epithelial cells produce and secrete CNP and whether CNP immunoreactivity is present in canine kidney. Opossum kidney (OK) cells that express proximal tubular cell characteristics were incubated for 6 h in fetal calf serum-free Dulbecco's modified Eagle's medium (DMEM). CNP immunoreactivity was measured in the preincubation and 6-h conditioned media by radioimmunoassay (RIA) using a specific antibody to CNP-22. Furthermore the molecular form of this CNP-like protein was determined by reverse-phase high-performance liquid chromatography (HPLC), and intracellular localization of the CNP immunoreactivity was determined by immunohistochemical staining. CNP immunoreactivity was also determined in renal tissue from dogs subjected to saline or endothelin infusion. Six-hour incubation in DMEM resulted in accumulation of CNP immunoreactivity (baseline below detection level vs. 6 h = 117.3 +/- 8.3 pg/ml, P < 0.001). Intracellular CNP concentration determined after sonication was 1.9 +/- 0.2 micrograms/g protein, and immunohistochemical staining for CNP was markedly positive in the cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood profile and balance study of rats given the putative anorectic agent satietin
Authors: Bellinger L. L. , Mendel V. E.
Published: December 2017

Satietin (SAT), a glycoprotein found in the plasma of a variety of animals, is a putative satiety agent. In experiments 1 and 2 rats received chronic third ventricle cannulas. At the start of the dark phase, in experiment 1, one group was infused with artificial cerebrospinal fluid (aCSF) and fed ad libitum (CON); a second group was infused with 100 micrograms/rat of human SAT and fed ad libitum in individual computerized pellet feeding modules; a third group was infused with aCSF and pair fed (PF) to the SAT-treated rats. The animals were killed 19.5 h later and blood was collected. Food and water intake and body weight were significantly, and comparably, reduced in the SAT-treated and PF group compared with the CON group. Plasma was assayed for a variety of nutrients, metabolites, enzymes, hormones, ions, and osmolality. Differential white cell counts were made. None of the above parameters differed significantly between the SAT and PF groups. Meal pattern analyses showed SAT treatment did not at any time alter meal size but significantly increased meal duration and intermeal interval during the first 6 h of the dark phase. In experiment 2 rats were placed in metabolic cages and infused with SAT or aCSF. Food and water intakes of the SAT group were suppressed for 1 day, whereas their body weights were significantly attenuated for 3 days. Urine volume and feces elimination were similar in the two groups over the 6-day measurement period. The normalcy of the data from experiment 1 is in accord with the possibility that SAT may act as a physiological satiety agent.(ABSTRACT TRUNCATED AT 250 WORDS)
Arterial and cardiopulmonary baroreflex control of renal nerve activity in cirrhosis
Authors: Rodriguez-Martinez M. , Sawin L. L. , DiBona G. F.
Published: December 2017

Cirrhotic rats (common bile duct ligation; CBDL) have increased efferent renal sympathetic nerve activity (ERSNA), which contributes significantly to the observed renal sodium and water retention and edema formation. Basal ERSNA is increased and fails to suppress normally during intravenous isotonic saline volume expansion. Arterial and cardiopulmonary baroreflex control of ERSNA in CBDL and control (CTR) rats was examined. CBDL rats exhibited hyperdynamic circulation with increased cardiac index and decreased total peripheral resistance index and arterial pressure compared with CTR rats. Increases in left ventricular end-diastolic pressure (LVEDP) produced by volume expansion increased cardiac index normally in CBDL rats. The maximal gain of aortic baroreflex control of ERSNA was similar in CBDL and CTR rats. In CBDL rats, during decreased arterial pressure, there was a decreased range of the central component, which accounted for the decreased range of the overall aortic baroreflex, with the range of the afferent component being normal. For cardiopulmonary baroreflex control of ERSNA, the LVEDP threshold was increased and the gain was decreased in CBDL compared with CTR rats; this was due to an increased LVEDP threshold and a diminished gain of the afferent component while the central portion of the reflex was normal. These abnormalities in the cardiopulmonary baroreflex account for the attenuated decrease in ERSNA in CBDL compared with CTR rats during volume expansion. In CBDL rats, attenuation of cardiopulmonary baroreflex control of ERSNA contributes to both the increased basal ERSNA and its failure to normally suppress during volume expansion.
Influence of nitric oxide on the hemodynamic response to hemorrhage in conscious rabbits
Authors: Koch M. A. , Hasser E. M. , Schadt J. C.
Published: December 2017

We investigated the role of nitric oxide, an endothelium-derived relaxing factor, in the hemodynamic response to acute hemorrhage in conscious rabbits. Chronically instrumented rabbits were treated with the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) or vehicle and hemorrhaged until mean arterial pressure fell below 40 mmHg. Control animals were treated with L-NAME or vehicle but not subjected to hemorrhage. L-NAME increased mean arterial pressure and decreased heart rate in control animals. Hindquarters and mesenteric blood flow velocity and conductance were reduced by L-NAME. Nitric oxide synthase inhibition also produced significant changes in the hemodynamic response to hypotensive hemorrhage. Mean arterial pressure was higher and regional vascular conductances were lower throughout hemorrhage and during recovery. L-NAME treatment significantly (but in some cases, subtly) altered the characteristic pattern of changes in vascular conductance associated with acute hypotensive hemorrhage and recovery. Similar experiments with other arginine analogues or phenylephrine infusion showed that L-NAME's effects during hemorrhage were due to nitric oxide synthase inhibition. We conclude that nitric oxide plays a role in the hemodynamic response to acute hemorrhage in the rabbit and is essential for the full expression of the vasodilation associated with hypotensive hemorrhage.
Aging and dietary modulation of elastase and interleukin-1 beta secretion
Authors: Cannon J. G. , Fiatarone M. A. , Meydani M. , Gong J. , Scott L. , Blumberg J. B. , Evans W. J.
Published: December 2017

Aging is associated with diminished immune function that may stem from alterations in arachidonic acid metabolism and lipid peroxidation. This study sought to determine if dietary modification of fatty acids influenced neutrophil and monocyte secretion after an in vivo inflammatory stress in older human subjects. Volunteers participated in protocols that forced their quadriceps muscles to lengthen during tension development (eccentric stress). These protocols can cause inflammatory foci in the muscle as well as alterations in circulating leukocyte function. In this study, in vivo neutrophil degranulation was assessed by plasma elastase concentrations, and mononuclear cell function was assessed by interleukin-1 beta (IL-1 beta) secretion in vitro. In response to eccentric stress, older subjects (> 60 yr old) taking a placebo had no apparent elastase response, whereas those taking fish oil supplements responded with a 142% increase in plasma elastase (P = 0.011), similar to responses of younger reference subjects (< 33 yr old) taking no supplement. Overall, elastase responses correlated with individual plasma arachidonic acid-to-eicosapentaenoic acid ratios (r = -0.881, P = 0.004). Thus apparent age-related differences in elastase release were reconciled by individual differences in fatty acid nutriture. No significant temporal changes in urinary lipid peroxide excretion or IL-1 beta secretion were observed; however, age-associated differences were found.
Neuronal excitation by angiotensin II in the rostral ventrolateral medulla of the rat in vitro
Authors: Li Y. W. , Guyenet P. G.
Published: December 2017

We examined the effects of angiotensin II (ANG II) on spontaneous unit activity in slices of the rat rostral ventrolateral medulla (RVLM), ANG II (1-3 microM) excited 61% of a population of slowly and irregularly firing RVLM neurons (predrug, 1.2 +/- 0.1 spikes/s; postdrug, 4.6 +/- 0.3 spikes/s; n = 52). ANG II had no effect on pacemaker-like rapidly firing neurons (predrug, 8.6 +/- 0.4 spikes/s; n = 33). The effect of ANG II on slowly firing cells was repeatable and was reduced 75% by 3 microM losartan (baseline, 1.7 +/- 0.4 spikes/s; ANG II, 5.3 +/- 0.7 spikes/s; ANG II+losartan, 2.4 +/- 0.6 spikes/s; n = 12). The ongoing activity of slowly firing neurons was unaffected by 0.5-1 mM kynurenic acid (an ionotropic excitatory amino acid receptor antagonist). Most ANG II-responsive neurons (10 of 11) were inhibited by the alpha 2-adrenergic receptor agonist UK-14,304, but pacemaker-like neurons were not. In conclusion, the RVLM contains neurons excited by AT1 receptor agonists. These neurons are distinct from the previously described pacemaker nonadrenergic presympathetic cells. They may be responsible for the pressor effects produced by injecting ANG II into the RVLM in vivo.
Aging effects on human sympathetic neuronal function
Authors: Esler M. D. , Turner A. G. , Kaye D. M. , Thompson J. M. , Kingwell B. A. , Morris M. , Lambert G. W. , Jennings G. L. , Cox H. S. , Seals D. R.
Published: December 2017

To study the effect of aging on human sympathetic nervous function, we applied kinetic methods for measuring the fluxes to plasma of neurochemicals relevant to sympathetic neurotransmission in younger (aged 20-30 yr) and older (aged 60-75 yr) healthy men. Mean plasma norepinephrine concentration was 66% higher in older men, attributable to 22% lower norepinephrine plasma clearance (P < 0.05) and 29% higher norepinephrine spillover to plasma (difference not statistically significant). Regional venous sampling disclosed that sympathetic outflow to all organs was not activated by aging. Renal norepinephrine spillover was normal in older men. Although spillover of norepinephrine from the heart was increased in older men, 21.1 +/- 11.4 ng/min compared with 11.4 +/- 8.6 ng/min (P < 0.05), diminished norepinephrine reuptake rather than increased cardiac sympathetic nerve firing was the most likely cause, although somewhat reduced intracardiac methylation of norepinephrine with aging also possibly contributed. The extraction of tritiated norepinephrine from plasma during transit through the heart was reduced, suggesting neuronal norepinephrine reuptake was lowered and overflow of the norepinephrine precursor dihydroxyphenylalanine and metabolites dihydroxyphenylglycol and 3-methoxy-4-hydroxy phenylglycol was normal, indicating that norepinephrine synthesis and release were not increased.
Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage
Authors: Iadecola C. , Zhang F. , Xu X.
Published: December 2017

We sought to determine whether expression of the inducible, calcium-independent isoform of nitric oxide synthase (iNOS) contributes to the tissue damage produced by focal cerebral ischemia. The middle cerebral artery was occluded in halothane-anesthetized spontaneously hypertensive rats. Twenty-four hours later rats received intraperitoneal injections of the iNOS inhibitor aminoguanidine (100 mg/kg twice per day; n = 10) or of aminoguanidine + L-arginine (300 mg/kg four times per day; n = 7), aminoguanidine + D-arginine (n = 7), arginine alone (n = 6), or vehicle (n = 9). Drugs were administered for 3 consecutive days. Infarct volume was determined by image analysis in thionin-stained brain sections 4 days after induction of ischemia. Administration of aminoguanidine reduced infarct volume by 33 +/- 4% (P < 0.05 from vehicle; analysis of variance and Tukey's test), a reduction that was antagonized by coadministration of L- but not D-arginine. Administration of L-arginine alone did not affect infarct size (P > 0.05 vs. vehicle). In separate rats (n = 10), aminoguanidine attenuated calcium-independent NOS activity in the infarct (P < 0.05 vs. vehicle) without affecting calcium-dependent activity (P > 0.05). Aminoguanidine did not affect resting cerebral blood flow or the cerebrovascular vasodilation elicited by hypercapnia, as determined by laser-Doppler flowmetry (n = 4). We conclude that aminoguanidine selectively inhibits iNOS activity in the area of infarction and reduces the volume of the infarct produced by middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatic denervation reduces adrenal catecholamine secretion during insulin-induced hypoglycemia
Authors: Lamarche L. , Yamaguchi N. , Peronnet F.
Published: December 2017

The present study was designed to investigate the functional implication of hepatic afferent nerves in controlling adrenal medullary counterregulatory response to insulin-induced hypoglycemia in anesthetized dogs subjected to an acute surgical denervation of the liver. Aortic glucose concentration decreased similarly in the groups of dogs with hepatic denervation (n = 8) and sham denervation (n = 8) reaching a glucose nadir 30 min after insulin injection (0.15 IU/kg i.v.) from a control value of 89.46 +/- 3.15 and 88.91 +/- 2.86 mg/dl to 52.92 +/- 3.27 and 48.80 +/- 4.18 mg/dl (P < 0.05), respectively. The catecholamine output from the adrenal glands in the sham group significantly increased (P < 0.05), reaching a maximum level 45 min after insulin injection from a control value for epinephrine of 86.35 +/- 26.65 ng/min and for norepinephrine of 32.14 +/- 11.68 ng/min to 659.03 +/- 269.39 and 181.21 +/- 63.03 ng/min, respectively. By contrast, however, adrenal catecholamine output increased only slightly in the hepatic-denervated group during insulin-induced hypoglycemia, from 148.37 +/- 95.29 and 52.06 +/- 28.05 ng/min to 210.49 +/- 96.09 and 79.61 +/- 26.11 ng/min for epinephrine and norepinephrine, respectively, the difference being statistically nonsignificant compared with the corresponding preinjection control value. The maximum net response of adrenal epinephrine and norepinephrine output observed in dogs with hepatic denervation was significantly attenuated by approximately 90 and 82% of the values obtained from the sham group, respectively. In a separate series of experiments, aortic immunoreactive insulin and glucagon concentrations were measured and found to be similar between hepatic-denervated and sham-denervated groups after insulin-induced hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Allometry of pharmacokinetics and pharmacodynamics of the muscle relaxant metocurine in mammals
Authors: Gronert G. A. , Fung D. L. , Jones J. H. , Shafer S. L. , Hildebrand S. V. , Disbrow E. A.
Published: December 2017

We investigated the effects of body size on the pharmacokinetics and pharmacodynamics of the renally cleared muscle relaxant metocurine. We hypothesized that pharmacokinetics of the drug would change allometrically in proportion to physiological time [infinity Mb0.25, where Mb is body mass] and that pharmacodynamics would be independent of size because of the highly conserved structure of the acetylcholine receptor. Metocurine effects during general anesthesia were examined in 17 rats, 8 cats, 6 dogs, 5 pigs, 7 sheep, and 12 horses. Allometric analysis demonstrated size dependence for pharmacokinetics, which were affected by physiological time (Mb0.25). Pharmacodynamics were size independent, except for the value for effect compartment concentration associated with 50% twitch paralysis (IC50). Data from individual species had a bimodal distribution that was significant: pigs and sheep were more sensitive than other large species, and their IC50 appeared size independent. IC50 was size dependent in more active species (horse, dog, cat, rat). Although the mechanism is unknown, we speculate that this trend might relate to receptor density within the end plate. Thus pharmacokinetics changed in proportion to physiological time, and pharmacodynamics were in part size independent.
DDAVP-induced maternal hyposmolality increases ovine fetal urine flow
Authors: Nijland M. J. , Ross M. G. , Kullama L. K. , Bradley K. , Ervin M. G.
Published: December 2017

Fetal urine flow is influenced by fetal intravascular volume, glomerular filtration rate, tubular reabsorption, and fluid regulatory hormones. As maternal-to-fetal fluid transfer is dependent on hydrostatic and osmotic gradients, we postulated that a chronic decrease in maternal plasma osmolality would promote transplacental fluid transfer and increase fetal urine flow. Six pregnant ewes and singleton fetuses (131 +/- 2 days; term = 150 days) received bladder and hindlimb arterial and venous catheters. After 5 days, plasma and urine composition, urine flow rate (Uvol), and plasma arginine vasopressin (AVP) levels were measured during a 2-h control period. At 2 h, tap water (2 liter, 38 degrees C) was administered to the ewe. At 3 h, ewes received a 20-micrograms bolus of 1-desamino-[D-Arg8]vasopressin (DDAVP), followed by continuous infusion (4 micrograms/h). In response to water loading, maternal urine osmolality decreased (761 +/- 158 to 339 +/- 13 mosmol/kgH2O), and Uvol increased. After DDAVP, maternal urine osmolality increased (1,270 +/- 89 mosmol/kgH2O), and Uvol, hematocrit, plasma osmolality (304 +/- 1 to 284 +/- 4 mosmol/kgH2O), and protein concentration decreased. Five hours after maternal DDAVP infusion, fetal plasma osmolality decreased (300 +/- 1 to 281 +/- 3 mosmol/kgH2O), and Uvol increased (0.4 +/- 0.1 to 1.3 +/- 0.2 ml/min) and remained elevated at 24 h. There was no change in fetal plasma DDAVP (immunoreactive AVP) levels or fetal urine osmolality. Controlled changes in maternal plasma osmolality may prove useful in modulating fetal urine flow and, ultimately, amniotic fluid volume.
Modulation of intrinsic cardiac neuronal activity by nitric oxide donors induces cardiodynamic changes
Authors: Armour J. A. , Smith F. M. , Losier A. M. , Ellenberger H. H. , Hopkins D. A.
Published: December 2017

Studies were performed to determine 1) whether a specific marker for nitric oxide production is associated with canine intrinsic cardiac neurons, 2) whether the transmembrane properties of these neurons can be altered by nitric oxide donors, 3) whether in situ intrinsic cardiac neurons are sensitive to nitric oxide donors, and 4) whether these neurons are involved in cardiac regulation. Thirty to forty percent of canine intrinsic cardiac neurons were labeled with a selective anatomic marker for nitric oxide production. Nitric oxide donors modified the transmembrane properties of a subpopulation of intrinsic cardiac neurons studied in vitro. The nitric oxide donors nitroglycerine, sodium nitrite, and nitroprusside induced concentration-dependent increases in neuronal activity frequently associated with cardiac augmentation. Similar neuronal responses were elicited by N-methyl-D-aspartate receptor activation as well as when the precursor of nitric oxide, L-arginine, and the exogenous nitric oxide donor, S-nitroso-N-acetylpenicillamine, were administered, indicating that intrinsic cardiac neurons can be modulated by nitric oxide donors. Such neurons apparently are tonically influenced by locally released nitric oxide as local administration of the competitive inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester, suppressed their spontaneous activity. These data indicate that a significant population of nitric oxide-sensitive neurons exists in the canine intrinsic cardiac nervous system that are involved in cardiac regulation.
Neuronal inhibition by a GABAB receptor agonist in the rostral ventrolateral medulla of the rat
Authors: Li Y. W. , Guyenet P. G.
Published: December 2017

We recorded the effects of the gamma-aminobutyric acid class B (GABAB) receptor agonist baclofen on neuronal activity in the rat rostral ventrolateral medulla (RVLM) in tissue slices and in vivo. In vitro, baclofen (3 microM) produced hyperpolarization (13 of 17), decrease in input resistance (12 of 16), and reduction of spontaneous synaptic activity (7 of 14). Baclofen inhibited 84 of 87 spontaneously active neurons recorded extracellularly in vitro. Inhibition was concentration dependent (0.1-3 microM, maximum inhibition: 94 +/- 4%, n = 16) and persisted in low-Ca2+/high-Mg2+ medium (n = 19). The GABAB receptor antagonists CGP-54626A (1 microM, n = 19), CGP-55845A (1 microM, n = 15), and 2-hydroxysaclofen (0.5 mM, n = 3) attenuated inhibition by baclofen (1-3 microM) but not by muscimol or GABA. In vivo, iontophoresis of baclofen inhibited 31 of 32 RVLM neurons, including bulbospinal barosensitive (15 of 16) and respiratory ones (7 of 7). CGP-55845A attenuated baclofen inhibition (6 of 9). Bicuculline attenuated the effect of GABA but not that of baclofen (4 of 4). In summary, RVLM presympathetic neurons have somatodendritic GABAB receptors that may contribute to baclofen-induced hypotension in humans.
Vasodilation evoked from medulla and cerebellum is coupled to bursts of cortical EEG activity in rats
Authors: Golanov E. V. , Reis D. J.
Published: December 2017

Cerebral blood flow (rCBF), measured by laser-Doppler flowmetry, spontaneously fluctuates at approximately 6 events/min in the anesthetized rat. These cerebrovascular waves (CWs) are preceded by simultaneous and synchronous bursts of electrocorticographic activity similar to burst-suppression/spindle-burst electroencephalogram patterns. Identical burst-CW complexes are evoked by single electrical pulses of specific sites in the cerebellar fastigial nucleus or rostral ventrolateral medulla. These consist, sequentially, of a constant initial triphasic (positive-negative-positive) potential reversing polarity in lamina V, variable afterbursts, and transient elevations of rCBF appearing approximately 1.2 s after burst onset. Evoked bursts are occluded by spontaneous bursts appearing < 50 s earlier. Procainization of the cortex reversibly blocks burst-CW complexes. Gradually increasing stimulus frequency proportionally increases the numbers of burst-CW complexes before rCBF rises. We conclude that spontaneous and evoked burst-CW complexes result from excitation of common neurons in lamina V. These intracortical “vasodilator” neurons are spontaneously excited by thalamocortical afferents generating burst-suppression electroencephalogram (EEG) patterns and excited reflexively by afferent signals from the fastigial nucleus or rostral ventrolateral medulla and couple intrinsic neuronal activity to local vascular mechanisms generating vasodilation.
Muscarinic stimulation maintains in vivo insulin secretion in response to glucose after prolonged hyperglycemia
Authors: Balkan B. , Dunning B. E.
Published: December 2017

Prolonged hyperglycemia impairs the in vitro insulin release by islets of Langerhans in response to glucose but exaggerates the in vivo insulin response. We hypothesized that this discrepancy results from increased vagal stimulation of the islets. Conscious chronically cannulated rats were infused with glucose (15 mg/min) or saline for 48 h. Three hours thereafter, an intravenous glucose tolerance test was performed with or without prior injection of atropine (0.2 mg). Atropine markedly (> 70%) reduced the insulin response in glucose-infused, but not in saline-infused, rats. Glucose-infused rats displayed basal hypoglycemia but normal glucose excursions during an intravenous glucose tolerance test. It is concluded that prolonged hyperglycemia produces exaggerated muscarinic activation of the beta-cells that will persist > or = 3 h after the termination of the glucose infusion and normalizes in vivo insulin secretion. It is possible that increased parasympathetic activation of the pancreas might constitute a general mechanism to maintain insulin output when the demand for insulin exceeds the inherent beta-cell responsiveness.
Effects of L-arginine-derived nitric oxide synthesis on neuronal activity in nucleus tractus solitarius
Authors: Ma S. , Abboud F. M. , Felder R. B.
Published: December 2017

The purpose of these studies was to determine the effects of L-arginine-derived nitric oxide (NO) synthesis on neuronal activity in solitary tract nucleus (NTS) neurons. Single unit activity was recorded extracellularly from medial NTS neurons in Fischer-344 rats in vivo and in vitro. In anesthetized rats with arterial pressure maintained constant, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv), an inhibitor of NO synthesis, decreased the discharge rate in 12 of 14 neurons and increased the discharge rate in two. After injection of L-NAME, the slowing of neuronal activity began within 2-5 min, and maximal responses were observed 12-15 min after injection. The decreases in activity were reversed within 12-15 min with L-arginine (30 mg/kg iv) or immediately with nitroglycerin (NTG, 10-30 micrograms/kg iv). In superfused rat brain slices, the discharge rate was reduced by 1 mM L-NAME in seven neurons, increased in two, and unchanged in one. The decreases in discharge rate were reversed by 2 mM L-arginine (4 of 6 neurons) and by 10-30 microM NTG (6 of 7 neurons). The results show that L-arginine-derived NO can affect the spontaneous discharge rate of NTS neurons. We conclude that NO may influence the excitability of NTS neurons involved in central autonomic control.
Neural control of glucose uptake by skeletal muscle after central administration of NMDA
Authors: Lang C. H. , Ajmal M. , Baillie A. G.
Published: December 2017

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.
Additive effects of obesity and hypertension to limit venous volume
Authors: Stepniakowski K. , Egan B. M.
Published: December 2017

The presence of reduced venous distensibility in obesity might have important hemodynamic effects and could indirectly implicate a role for metabolic factors in vascular control, because loading conditions are different in arterial and in venous vessels. Forearm blood flow and venous volume were measured plethysmographically in 58 subjects, including lean and obese hypertensives and normotensives. Venous volume at 30 mmHg (VV30) was decreased by both obesity and hypertension. This coincided with evidence for better preservation of central blood and stroke volumes with upright posture in obese than in lean subjects. Furthermore, obese hypertensives had lower VV30 than either lean hypertensives or obese normotensives. Postischemic forearm vascular resistance, a surrogate marker for structural luminal cross-sectional area, percent body fat, and fasting insulin each correlated independently with VV30 (P < 0.05) in multivariate analysis. Because nonesterified fatty acid levels are elevated in obese hypertensives and may have potent vascular effects, dorsal hand vein responses to coinfusion of Intralipid 10% and heparin to raise fatty acids locally were obtained in normal volunteers. The local infusion of Intralipid with heparin reduced hand vein distensibility, whereas dextrose and heparin did not (11 +/- 3% vs. 0 +/- 2%, respectively, P < 0.01). This study indicates that obesity and mild hypertension each reduce venous distensibility and that the coexistence of both conditions produces an even greater impairment in venous capacitance. The reduced venous distensibility in obesity appears to reflect structural as well as functional factors and to have systemic hemodynamic effects.
Effect of somatolactin and related hormones on phosphate transport by flounder renal tubule primary cultures
Authors: Lu M. , Swanson P. , Renfro J. L.
Published: December 2017

Winter flounder renal proximal tubule primary monolayer cultures mounted in Ussing chambers were used to determine the effect of salmon somatolactin (sSL) on transepithelial Pi and Ca2+ transport. sSL stimulated Pi reabsorption in a dose-dependent manner at physiological levels of the hormone (12.5 ng/ml). Net Pi transport was significantly altered by sSL (200 ng/ml) within 2 h after the initial exposure. Ca2+ fluxes were unchanged by the addition of 200 ng/ml sSL. The sSL-induced Pi reabsorption was abolished by 10 microM H-89, a highly specific protein kinase A inhibitor. Moreover the production and release of adenosine 3',5'-cyclic monophosphate were significantly increased after 1 and 2 h of exposure to sSL. The data indicate that sSL directly stimulates net renal Pi reabsorption by an adenosine 3',5'-cyclic monophosphate-dependent pathway. In addition to sSL, flounder SL and rat prolactin greatly, and salmon growth hormone (2.3 micrograms/ml) slightly, increased net Pi reabsorptive flux, whereas salmon prolactin had no effect.
Dietary obesity in the mouse: interaction of strain with diet composition
Authors: West D. B. , Waguespack J. , McCollister S.
Published: December 2017

The effect of varying dietary macronutrient content on the body composition of AKR/J and SWR/J mice was examined. Dietary fat was fed at three levels (45, 30, and 15 kcal%), while dietary protein also was varied across three levels (10, 20, and 30 kcal%). All mice were placed on the defined diets at 5 wk of age and maintained on these diets for 12 wk. AKR/J mice were significantly larger and had a significantly greater carcass fat content compared with SWR/J mice in all dietary conditions. There was a clear dose-response effect of dietary fat on body fat in the AKR/J mice. In contrast, SWR/J mice showed an increase of body fat only when fed the diet containing the highest level of dietary fat and the lowest protein concentration. High levels of dietary protein (30 kcal%) resulted in a significant decrease of carcass fat in the AKR/J mice compared with diets containing either 20 or 10 kcal% protein. This effect of protein was not observed in the SWR/J mice except in the groups fed the 45 kcal% fat diets. These findings demonstrate a strong interaction of genetic background and macronutrient content of the diet on body composition. The AKR/J strain of mouse has a greater percentage of carcass fat and is more responsive to the effects of dietary fat composition compared with the SWR/J strain.
Electrical stimulation and amino acid and ammonia metabolism in the canine gastrocnemius muscle
Authors: MacLean D. A. , Barclay J. K. , Graham T. E.
Published: December 2017

This study examined the effects of electrical stimulation on amino acid and ammonia (NH3) metabolism in the isolated in situ canine gastrocnemius muscle preparation. Cut sciatic nerves of 10 mongrel dogs were stimulated at either 3 or 5 twitches/s (10 V, 0.2-ms duration) for 60 min. Muscle NH3 release dramatically increased on stimulation, and over 60 min the 3- and 5-Hz groups released 86.7 +/- 24.2 vs. 160.8 +/- 17.4 mumol.min-1.100 g-1 (P < 0.05) of NH3, respectively. Similarly, the intramuscular NH3 concentration was elevated (P < 0.05) above rest for both groups throughout stimulation, and it was higher (P < 0.05) at 5 min for the 5-Hz (82.7 +/- 2.4 mumol/100 g wet wt) than for the 3-Hz (67.4 +/- 7.4 mumol/100 g wet wt) group. Stimulation was also characterized by a large release of amino acids by both groups. The total amino acid release for 60 min was 415.4 +/- 64.9 vs. 193.3 +/- 56.2 (P < 0.05) mumol/100 g for the 3- and 5-Hz groups, respectively. However, there were no shifts or differences between groups in the intramuscular total amino acid pools. Glutamine (Gln) and alanine (Ala) dominated the amino acids released by muscle and together represented 35 and 46% of the total amino acids released over 60 min for the 3- and 5-Hz groups, respectively. The total release of Gln was higher (P < 0.05) for the 3-Hz (81.1 +/- 5.6 mumol/100 g) than for the 5-Hz (49.4 +/- 10.7 mumol/100 g) group, but there were no differences between groups in total Ala release. In contrast, both groups demonstrated an uptake of branched-chain amino acids (valine, isoleucine, and leucine) after 45 min of stimulation. These data show a stimulation-dependent production of NH3 and release of amino acid by the canine gastrocnemius muscle. These data further show that the degree of net muscle NH3 production is proportional to the frequency, whereas the degree of amino acid release is an inverse function of frequency.
Nitric oxide responses of air-breathing and water-breathing fish
Authors: Staples J. F. , Zapol W. M. , Bloch K. D. , Kawai N. , Val V. M. , Hochachka P. W.
Published: December 2017

Nitric oxide (NO), exogenously administered or endogenously produced by NO synthase (NOS), is an important regulator of lung ventilation and perfusion in mammals. This study attempts to investigate the evolutionary history of this system in fish and its possible relationship to air breathing. The gas bladder of Hoplerythrinus unitaeniatus (air-breathing teleost) and Oncorhynchus mykiss (non-air-breathing teleost) and the lung of Lepidosiren paradoxa (air-breathing dipnoan) all exhibited elevated guanosine 3',5'-cyclic monophosphate (cGMP) levels in response to 1 microM sodium nitroprusside. Only the H. unitaeniatus gas bladder responded to 10 microM acetylcholine chloride (ACh) with increased cGMP levels. The ACh response was inhibited by N omega-nitro-L-arginine methyl ester, which inhibits NOS. These data suggest that although tissues from each species may respond to exogenous NO, only the gas bladder of H. unitaeniatus appears to synthesize NO through NOS. This is the first report of constitutive NOS outside of the central nervous system in a teleost. These results also imply that NOS did not necessarily coevolve with air breathing in fish.
Different outcomes in biological experiments involving weak EMFs: is chaos a possible explanation?
Authors: Marino A. A.
Published: December 2017

Reports of biological effects induced by electromagnetic fields (EMFs) are sometimes not confirmed in subsequent similar studies. It is possible that the fields in these studies were actually transduced by the biological systems and that the pattern of apparently conflicting results is not a valid inference but arises from the conceptual framework. The question was studied in connection with effects of EMFs on body weight of animals. Previous studies revealed no consistent effect on mean body weight, but reexamination of the data suggested that variance in body weight was consistently altered after long-term exposure. In the present study, 0.5 kV/m, 60 Hz, was applied continuously from conception to maturity in successive generations of mice; as hypothesized, mean body weight was not consistently affected but variance in body weight was altered. The occurrence of transduction can therefore be inferred from the effect on variance despite the absence of a consistent effect on the mean. These results and those from previous similar studies support an interaction model in which the observability of posttransduction biological changes in the mean is strongly dependent on the initial conditions, in analogy with the importance of initial conditions in fixing the final state in deterministic chaos. Thus, at least with regard to EMF effects on body weight, a change from a linear (dose-effect) to a nonlinear paradigm is sufficient to explain the anomalous pattern of some reported studies.
Substance P increases microvascular permeability via nitric oxide-mediated convective pathways
Authors: Nguyen L. S. , Villablanca A. C. , Rutledge J. C.
Published: December 2017

The goal of these studies was to examine the effects of substance P, a tachykinin neuropeptide, on pathways of microvascular permeability. Individual frog mesenteric venular capillaries were cannulated, and albumin apparent permeability coefficients (Ps) were determined by quantitative fluorescence microscopy. Ps of albumin (PsAlb) rose from 6.8 +/- 1.8 (SE) cm.s-1.10(7) at control to 22.3 +/- 2.3 cm.s-1.10(7) when substance P (10(-11) M) was perfused. The effect of increased microvessel permeability induced by substance P (10(-11) M) was blocked with the nonpeptide substance P receptor antagonist CP-96,345 and NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. PsAlb increased 0.99 cm.s-1.10(7) for every cmH2O increase in microvessel pressure after treatment of the vessel with substance P, demonstrating coupling of albumin flux to transvascular water flow. In conclusion, the mechanism of increased microvessel permeability in response to substance P appears to be the result of receptor-mediated increase in nitric oxide production and formation of water-filled convective pathways presumably located between adjacent endothelial cells.
Effects of baroreceptor reflex on efferent pulmonary sympathetic nerve activity in anesthetized cat
Authors: Shirai M. , Matsukawa K. , Nishiura N. , Ninomiya I.
Published: December 2017

We analyzed the baroceptor reflex effect on efferent pulmonary sympathetic nerve activity (PSNA) in anesthetized cats. PSNA was recorded from the central end of the cut nerve bundle, which was isolated from the lobar artery supplying the diaphragmatic lobe. Renal sympathetic nerve activity (RSNA) and aortic blood pressure (AP) were also simultaneously measured. There were grouped discharges synchronous with cardiac cycle and its respiratory modulation in PSNA. In a given cardiac cycle, the discharge patterns differed between the pulmonary and renal nerves. Average sympathetic nerve activity and AP obtained from 100 consecutive cardiac cycles showed that the baroreceptor reflex delay time on the pulmonary nerve (266 ms) was longer than that on the renal nerve (195 ms). The data indicate nonuniformity in the cardiac-related PSNA and RSNA. The grouped PSNA disappeared with hexamethonium bromide, indicating that PSNA originates from postganglionic efferent fibers. To examine the baroreflex response of PSNA, AP was increased by 70 mmHg with phenylephrine and decreased by 70 mmHg with nitroprusside. PSNA changed inversely to the changes in mean aortic pressure (MAP). In the delta MAP-delta PSNA curve, delta PSNA reached the maximum level (74%) and the noise level at -56 +/- 4 and 58 +/- 4 mmHg, respectively. The mean slope of the curve was 1.5 +/- 0.1%/mmHg. RSNA also responded inversely to the MAP change.(ABSTRACT TRUNCATED AT 250 WORDS)
Cortisol, ACTH, and cardiovascular response to a cognitive challenge paradigm in aging and depression
Authors: Gotthardt U. , Schweiger U. , Fahrenberg J. , Lauer C. J. , Holsboer F. , Heuser I.
Published: December 2017

Aging and hypercortisolism may be associated with alterations of stress-induced hormone release. We therefore studied 20 normal controls of two different age groups (< 30 and > 60 yr of age) and 20 age-matched patients with major depression; baseline ACTH and cortisol secretion (between 1400 and 1700) as well as blood pressure and heart rate and their responses to a 45-min lasting signal detection task (1705-1750) were determined. No difference in basal hypothalamic-pituitary-adrenal (HPA) system activity between young and older healthy controls was noted. The cognitive challenge resulted in an increase in stress-induced hormonal secretion that was greater in the older controls than in their young counterparts. Basal hypercortisolemia and, at baseline, heart rates were higher in depressed patients, regardless of age. Blood pressure was elevated in older healthy controls as well as depressed patients. With the exception of the young depressed patients, all groups responded with an increase of the cardiovascular parameters during stress.