bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasopressin and renin-angiotensin maintain arterial pressure during PEEP in nonexpanded, conscious dogs
Authors: Kaczmarczyk G. , Vogel S. , Krebs M. , Bunger H. , Scholz A.
Published: December 2017

Increases of plasma arginine vasopressin (AVP) and plasma renin activity (PRA) during controlled mechanical ventilation (CMV) with positive end-expiratory pressure (PEEP) induce positive fluid balances by decreasing renal excretion. We investigated whether elevated levels of AVP and/or PRA maintain mean arterial pressure (MAP) during PEEP under conditions where plasma volume is not expanded. Six conscious chronically tracheotomized beagle dogs, kept under standardized conditions, were investigated in four protocols. They were 1) control: 1 h spontaneous breathing with a continuous positive airway pressure of 4 cmH2O (CPAP 4) followed by 2 h CMV with PEEP, resulting in a mean airway pressure of approximately 20 cmH2O (CMV 20 referred to as "PEEP"); 2) vasopressin blockade: 1 h CPAP 4, 2 h PEEP after intravenous application of an AVP V1-receptor antagonist (AVPA); 3) converting enzyme inhibition: 1 h CPAP 4, 2 h PEEP plus angiotensin-converting enzyme inhibition (ACEI); and 4) combined blockade: 1 h CPAP 4, 2 h PEEP plus AVPA + ACEI. In AVPA + ACEI, MAP decreased during PEEP from 101 +/- 4 to 75 +/- 10 mmHg, glomerular filtration rate (GFR) decreased from 3.6 +/- 0.3 to 1.7 +/- 0.7 ml.min-1.kg body wt-1, heart rate increased from 95 +/- 10 to 122 +/- 7 beats/min, plasma aldosterone increased from 62 +/- 26 to 353 +/- 63 pg/ml, plasma epinephrine increased from 81 +/- 15 to 352 +/- 89 pg/ml (all changes P < 0.05), and plasma norepinephrine did not change. Neither MAP nor GFR changed during PEEP in control experiments in which both PRA and AVP increased, in AVPA experiments in which PRA increased, or in ACEI experiments in which AVP increased. We conclude that both AVP and angiotensin II contribute to the maintenance of MAP and GFR during PEEP. When both hormones are inhibited, no immediate compensation exists to prevent an acute fall in MAP and GFR.
Cachectic effect of ciliary neurotrophic factor on innervated skeletal muscle
Authors: Martin D. , Merkel E. , Tucker K. K. , McManaman J. L. , Albert D. , Relton J. , Russell D. A.
Published: December 2017

Recombinant human ciliary neurotrophic factor (rh-CNTF) was reported to attenuate skeletal muscle wasting in rats after unilateral transection of the sciatic nerve (M. E. Helgren, S. P. Squinto, H. L. Davis, D. J. Parry, T. G. Bolton, C. S. Heck, Y. Zhu, G. D. Yancopoulos, R. M. Lindsay, and P. S. DiStefano. Cell 76: 493-504, 1994). Under the experimental conditions reported herein, the absolute masses of the denervated gastrocnemius and soleus muscles were not increased in mature or immature rats of either sex by treatment with rhCNTF. At the highest doses of rhCNTF (1 and 0.1 mg/kg), increases in the ratio of the masses of the denervated to the contralateral innervated gastrocnemius and soleus muscles could be attributed entirely to a muscle-wasting effect on the contralateral innervated muscle rather than any muscle-sparing effect on the denervated muscle. The muscle-wasting effects of rhCNTF were associated with reductions in body weight gain and reduced food intake. Pair-fed rats lost less body weight and skeletal muscle mass than rhCNTF-injected freely fed rats but experienced significantly greater loss of visceral mass. Male rats displayed greater loss of body weight and skeletal muscle mass than female rats. Recombinant inhibitors of the cachectic cytokines, tumor necrosis factor and interleukin-1, did not significantly alter the wasting effects of rhCNTF. These findings demonstrate that, in contrast to its well-characterized trophic effects on cells of the nervous system, rhCNTF causes atrophy of skeletal muscle by mechanisms involving both anorexia and cachexia based on the results of pair-feeding experiments.
Angiotensin II and the maturation of renal cortical Na+/H+ exchanger activity during fetal life in sheep
Authors: Guillery E. N. , Mathews M. S. , Orlowski J. , Robillard J. E.
Published: December 2017

The postnatal rise in renal Na+ reabsorption is associated with an increase in proximal tubule apical membrane Na+/H+ exchanger (NHE) activity in sheep. Inasmuch as circulating angiotensin II (ANG II) levels increase immediately after birth and ANG II is known to upregulate NHE activity in the adult proximal tubule, we postulated that ANG II plays a role in mediating maturational changes in NHE activity. We therefore studied the effects of ANG II infusion (10 micrograms/h) for 24 h on renal cortical NHE activity in chronically instrumented, twin ovine fetuses (129 +/- 2 days gestation, term is 145 days, n = 10 pairs); one twin of each pair served as a control. After 24 h, the fetuses were killed and brush-border membrane vesicles (BBMV) were prepared from the renal cortices. Postinfusion plasma ANG II levels were significantly higher and plasma renin activities were significantly lower in treated fetuses compared with controls. Kinetic analysis revealed an increase in NHE activity after ANG II treatment; however, the difference was not statistically significant: maximal velocity (in nmol.s-1.mg protein-1) control 1.65 +/- 0.50, treated 2.31 +/- 0.66 (P = 0.11, n = 9 pairs); Michaelis constant control 8.29 +/- 1.17 mM, treated 9.84 +/- 1.26 mM (P = 0.11). Northern blots of total RNA from the cortices of these animals were hybridized to a D-[32P]UTP-labeled antisense RNA probe prepared from a 1.3-kb rat NHE3 cDNA fragment. There were no differences between the groups in NHE3 mRNA levels (32P counts were control 413 +/- 54, treated 340 +/- 46). ANG II does not appear to play an important role in the regulation of NHE activity in the proximal tubule of the near-term sheep fetus.
Mechanisms of maternofetal chloride transfer across the human placenta perfused in vitro
Authors: Doughty I. M. , Glazier J. D. , Greenwood S. L. , Boyd R. D. , Sibley C. P.
Published: December 2017

To determine the relative contribution of the paracellular and transcellular routes to Cl-transfer, unidirectional maternofetal clearance (Kmf) of 36Cl was compared with Kmf of 51Cr-EDTA and creatinine across the human placenta perfused in vitro. The effect of C1-transport inhibitors 4,4'-diisothiocyanostilbene-2,2-disulfonic acid (DIDS) and diphenylamine-2-carboxylate (DPC) was also investigated. The diffusion coefficient (D) was estimated for each solute by use of an agar diffusion method. At steady state, Kmf/D for 36Cl (0.070 +/- 0.003 cm, n = 23) was not different from that for 51Cr-EDTA (0.070 +/- 0.003 cm, n = 23), and Kmf/D was significantly higher for creatinine than for 36Cl and 51Cr-EDTA (0.087 +/- 0.003 cm, n = 20, P < 0.001). Addition of the inhibitors DIDS and DPC to the perfusates resulted in a small but significant rise in Kmf of 51Cr-EDTA (0.41 +/- 0.03 vs. 0.49 +/- 0.02 ml/min, n = 16, P < 0.0001) and creatinine (0.66 +/- 0.05 vs. 0.74 +/- 0.04 ml/min, n = 13, P < 0.001), but Kmf of 36Cl was unchanged (1.11 +/- 0.07 vs. 1.13 +/- 0.05 ml/min, n = 16). There was no change in Kmf of any solute with time in control experiments. From these data, DIDS- and DPC-inhibitable fractions of Kmf for 36Cl were estimated and together accounted for 16% of total clearance. This study suggests that maternofetal flux of 36Cl across the in vitro perfused human placenta occurs predominantly, but not solely, via paracellular routes.
Leptin reduces juvenile fat stores by altering the circadian cycle of energy expenditure
Authors: Stehling O. , Doring H. , Ertl J. , Preibisch G. , Schmidt I.
Published: December 2017

The recently identified hormone leptin (ob protein) secreted by white adipose tissue is widely thought to provide a feedback signal limiting fat storage by decreasing food intake. By artificially rearing leptin-treated and control littermates fed identical amounts of milk, however, we show here that lean suckling-age rats treated with recombinant murine leptin can reduce fat storage solely by increasing energy expenditure. Continuous measurements of core temperature and metabolic rate show that this increase is not uniform throughout the day but is especially prominent in the morning when rat pups usually conserve energy by entering a torpor-like state. Leptin's alleviation of hypometabolic, torpor-like states is thus not restricted to cases of impaired hormone production but seems instead to be a normal biological function independent of its effects on food intake.
Medullary pathways mediating depressor responses from Na(+)-sensitive sites in nucleus of the solitary tract
Authors: Hochstenbach S. L. , Ciriello J.
Published: December 2017

Two series of experiments were done in male Wistar rats to investigate the medullary pathways that mediate the depressor responses from sodium-sensitive sites in the nucleus of the solitary tract (NTS). In the first series, the anterograde tract tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was iontophoresed unilaterally at sites in the NTS at which microinjections (20 nl) of a 154-175 mM NaCl solution elicited depressor responses. PHA-L injection sites were found to be localized within the medial subnucleus of the NTS (Sm). In the medulla, PHA-L-labeled fibers and presumptive terminal boutons were observed bilaterally, but with an ipsilateral predominance, throughout the rostrocaudal extent of the NTS the dorsal motor nucleus of the vagus, area postrema, the ventrolateral medulla (VLM), and nucleus ambiguus. The pontine region, containing the A5 catecholaminergic cell group and the parabrachial nucleus, also received projections from Sm. In the second series of experiments, the effect of blocking synaptic transmission in VLM with cobalt chloride (CoCl2; 5 mM, 100 nl) on the cardiovascular response elicited by microinjection (20 nl) of hypertonic saline (154-175 mM) into the ipsilateral Sm was investigated in the alpha-chloralose-anesthetized, paralyzed, and artificially ventilated rat. Microinjection of CoCl2 into VLM, at sites shown in the previous study to receive efferent projections from Sm, significantly attenuated the depressor (60%) and bradycardic (80%) responses to stimulation of Sm. These data indicate that the sodium-sensitive region of the caudal Sm innervates VLM neurons and suggest that these VLM neurons are involved in mediating the depressor and bradycardic responses elicited by changes in the extracellular concentration of sodium.
Contribution of energy intake and tissue enzymatic profile to body weight gain in high-fat-fed rats
Authors: Gayles E. C. , Pagliassotti M. J. , Prach P. A. , Koppenhafer T. A. , Hill J. O.
Published: December 2017

The purpose of the current study was to examine the enzymatic profile [phosphofructokinase (PFK), beta-hydroxyacyl-CoA dehydrogenase (HADH), and citrate synthase (CS)] in gastrocnemius muscle, heart, and liver in rats allowed ad libitum access to a high-fat diet (HFD, 45% of kcal from corn oil). Male Wistar rats were fed a low-fat diet (LFD, 12% of kcal from corn oil) for a 2-wk baseline period after which some continued on the LFD and others were placed on the HFD. After 1 wk on the HFD, rats were categorized as obesity-resistant (OR), -intermediate (OI), or -prone (OP) on the basis of body weight gain (OR, lower tertile; OI, middle tertile; OP, upper tertile). At 1, 2, and 5 wk, rats from each group were killed (n = 9-14 from each group/time point) after a 24-h fast. At the end of the 5-wk dietary period, weight gain was 114.8 +/- 4.3 in LFD, 125.2 +/- 3.7 in OR, 147.1 +/- 4.1 in OI, and 173.7 +/- 3.5 g in OP rats (OP > OI > OR, LFD; P < 0.001). Energy intake was highly correlated with weight gain on the HFD at each time point (r > or = 0.72, P < 0.001). After 1 wk on the HFD, significant correlations between the ratio of PFK/HADH (an indication of the relative capacity for glycolysis vs. beta-oxidation, r = 0.4, P = 0.03) and HADH/CS (an indication of the capacity for beta-oxidation relative to total oxidative capacity, r = -0.56, P = 0.001) in the gastrocnemius muscle and weight gain were observed. At week 2, significant correlations between these ratios and weight gain were observed in the gastrocnemius, liver, and heart. In contrast, these ratios were not significantly correlated with weight gain at 5 wk. These results suggest that rats most susceptible to weight gain or a HFD are characterized by a continuous increase in energy intake (explaining approximately 50% of the variance in weight gain) and an early tissue enzymatic profile that favors carbohydrate over fat use.
H(+)-glycyl-L-proline cotransport in brush-border membrane vesicles of eel (Anguilla anguilla) intestine
Authors: Maffia M. , Verri T. , Danieli A. , Thamotharan M. , Pastore M. , Ahearn G. A. , Storelli C.
Published: December 2017

A plasma membrane H(+)-glycyl-L-proline (Gly-L-Pro) cotransport mechanism has been identified in isolated eel intestinal brush-border membrane vesicles (BBMV) by both measuring radiolabeled Gly-L-Pro uptake and monitoring Gly-L-Pro-dependent H+ influx with the pH-sensitive dye acridine orange. The application of an inside negative membrane potential resulted in increasing Gly-L-Pro uptake, as well as the application of inwardly directed H+ gradient (although only when an inside negative membrane potential was present). Furthermore, vesicular H+ influx was found specifically associated with the presence of Gly-L-Pro in the extravesicular medium. The carrier-mediated nature of H(+)-Gly-L-Pro cotransport was assessed, and its concentration that yielded one-half maximal Gly-L-Pro influx was approximately 1.30 mM when measured by either radioactive or fluorescent tracers. Different dipeptides strongly inhibited Gly-L-Pro uptake by eel intestinal BBMV, as well as the cephalosporin antibiotic cephalexin, suggesting that dipeptide molecules and cephalosporin antibiotics may share a common transport system in eel intestinal BBMV.
Contemporaneous melatonin administration modifies the circadian response to nocturnal bright light stimuli
Authors: Cagnacci A. , Soldani R. , Yen S. S.
Published: December 2017

We investigated whether the contemporaneous administration of melatonin can modify circadian phase shifts induced by bright light stimuli. After a baseline evaluation, 10 women were exposed for three consecutive nights to a 4-h bright light stimulus (>3,000 lx) initiated at the time of the estimated core body temperature (BT(c)) nadir. Along with light, each woman orally received, randomly and in a double-blind fashion, placebo (n = 5) or melatonin (n = 5; 1 mg 30 min before and 0.75 mg 120 min after the start of light exposure). Daily rhythms were reevaluated at the end of treatment. Bright light phase advanced, by about 90-120 min, BT(c) (P < 0.01), cortisol (P < 0.05), and melatonin (P < 0.01) rhythms. Contemporaneous administration of melatonin antagonized the phase advances of the cortisol and BT(c) rhythms, as well as the melatonin peak and melatonin offset. The phase advance of the melatonin onset was instead enhanced (P < 0.05). Contemporaneous melatonin administration modifies the capability of light to induce circadian phase shifts.
Role of pulmonary stretch receptor feedback in control of episodic breathing in the bullfrog
Authors: Kinkead R. , Milsom W. K.
Published: December 2017

This study compared the "fictive" breathing patterns of decerebrate, paralyzed, unidirectionally ventilated bullfrogs in which pulmonary stretch receptor (PSR) feedback was either absent bilateral vagotomy), maintained constant at different levels (tonic) or oscillated with each fictive breath (phasic) under different levels of hypoxic or CO2-related respiratory drive. Tonic and phasic PSR feedback had identical effects on the fictive breathing pattern; decreasing PSR feedback increased the peak integrated trigeminal electroneurogram recordings and decreased breathing frequency. The effects of bilateral vagotomy and lung deflation to 0 cmH2O on breathing pattern were identical. Although hypoxia (fractional concentration of O2 in air = 0.06) had no significant effect on fictive breathing, ventilating frogs with increasing CO2 levels (fractional CO2 concentration in inspired air range: 0.00-0.03) increased the number of breaths in each fictive breathing episode, and this effect was potentiated by PSR feedback. Whenever respiratory drive was increased, regardless of the method (increase in PSR feedback or chemoreceptor drive), occasional single breaths were replaced by breathing episodes, indicating that the mechanisms responsible for the clustering of the breaths and the onset/termination of breathing episodes are not dependent on either input alone.
Pregnancy increases ET-1-induced contraction and changes receptor subtypes in uterine smooth muscle in humans
Authors: Osada K. , Tsunoda H. , Miyauchi T. , Sugishita Y. , Kubo T. , Goto K.
Published: December 2017

The purpose of the present study was to investigate whether pregnancy affects endothelin (ET)-1-induced contraction, the density ofET receptors, and the ratio of receptor subtypes (ET(A) and ET(B)) in uterine smooth muscle in humans. We also investigated which ET receptor subtypes mediate ET-1-induced contraction in the human uterus. In uterine membrane preparations, (125)I-labeled ET-1 ((125)I-ET-1) binding sites (Bmax) in pregnant women did not differ from those in age-matched nonpregnant women (596.2 +/- 107.1 vs. 512.1 +/- 167.7 fmol/mg protein). The dissociation constant (Kd) in pregnant women did not differ from that in nonpregnant women. Competitive displacement experiments with (125)I-ET-1 binding to the membranes using BQ-123 (ET(A) receptor antagonist) showed that the percentage of ET(A) receptors in uterine muscle was significantly higher in pregnant women than in nonpregnant women (P < 0.01). The calculated ratios of ET(A) to ET(B) receptors in pregnant and nonpregnant uteri were 92:8 and 68:32, respectively. Combination treatment with BQ-788 (ET(B) receptor antagonist) completely inhibited the BQ-123-resistant component of (125)I-ET-1 specific binding. ET-1 caused dose-dependent contractions in isolated human uteri from both pregnant and nonpregnant women. The maximum response was markedly greater in pregnant women than in nonpregnant women, whereas pD2 (-log[EC50]) values did not differ between pregnant and nonpregnant uteri. In pregnant human uterus, BQ-123 (10(-6) M) significantly shifted the dose-dependent curve of ET-1 response to the right, whereas BQ-3020 (ET(B) receptor agonist) did not cause contraction. These results suggested that ET-1-induced contraction of the human uterus is mediated through only ET(A) receptors and that ET-1-induced uterine contraction in humans is markedly increased during pregnancy. In addition, the present study suggests that, although (125)I-ET-1 Bmax are not altered during pregnancy, the proportion of ET(A) receptors is increased and that of ET(B) receptors is decreased in the pregnant human uterus.
Stimulation of dog RVLM and A5 area changes sympathetic outflow to vascular beds without effect on the heart
Authors: Dickerson L. W. , Panico W. H. , Kuhn F. E. , Willis A. C. , Fitzgerald J. F. , Meyer E. L. , Norman W. P. , Gillis R. A.
Published: December 2017

Studies were conducted in anesthetized, vagotomized dogs while blood pressure; blood flows in femoral, renal, mesenteric, and left circumflex coronary arteries; electrocardiogram; and regional cardiac contractile force were monitored. The ventral surface of the medulla was exposed, and pressor sites in the rostral ventrolateral medulla (RVLM) were mapped by microinjections of L-glutamate. L-Glutamate activation of the RVLM evoked selective effects on different components of the cardiovascular system. Increases of 20-130 mmHg in blood pressure were accompanied by vascular conductance decreases in the femoral (-48 +/- 4%), renal (-30 +/- 4%), and mesenteric (-38 +/- 3%) arterial beds. These effects were without any obvious topography within the RVLM. There were only small or negligible changes in heart rate (HR), cardiac contractile force, and coronary vascular conductance. Thus stimulation of the canine RVLM increased sympathetic tone selectively to structures other than the heart. Stimulation of the ventral medulla in a region that lay rostral to the RVLM and ventromedial to the facial nucleus selectively increased femoral vascular conductance by 103 +/- 33% and decreased vascular conductance in the renal (-20 +/- 5%) and mesenteric (-15 +/- 4%) arterial beds. There was no increase in HR, and the increases in blood pressure were relatively small. Immunohistochemical data led us, tentatively, to identify this rostral area as overlapping part of the A5 area.
Role of nitric oxide in the arterial pressure and renal adaptations to long-term changes in sodium intake
Authors: Manning R. D. , Hu L. , Reckelhoff J. F.
Published: December 2017

The goals of this study were to determine whether long-term nitric oxide (NO) synthesis inhibition in dogs results in an increase in the sodium sensitivity of arterial pressure and whether changes in plasma renin activity or the plasma concentrations of arginine vasopressin (AVP) and aldosterone play an important role in this hypertension. Studies were conducted in a control group and groups that received NO inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) at 10 or 25 microg x kg(-1) x min(-1). Each group was challenged with normal, low, and high sodium intake for periods of 5 days each. Urinary nitrate + nitrite excretion (UNOx) more than doubled in the control group during high sodium intake. In both L-NAME groups, UNOx decreased significantly, there was a hypertensive shift in the relation between urinary sodium excretion and arterial pressure, and urinary sodium excretion remained normal even in the high-sodium intake period. L-NAME infusion did not change the sodium sensitivity of arterial pressure or plasma renin activity, plasma aldosterone, and plasma AVP. In conclusion, the data suggest that, in dogs, increases in NO synthesis are not necessary to excrete a chronic sodium load, and decreases in NO do not increase the sodium sensitivity of arterial pressure.
Early evening melatonin and S-20098 advance circadian phase and nocturnal regulation of core body temperature
Authors: Krauchi K. , Cajochen C. , Mori D. , Graw P. , Wirz-Justice A.
Published: December 2017

The phase-shifting capacity and thermoregulatory effects of a single oral administration at 18 h of melatonin (5 mg) or S-20098, a melatonin agonist (5 or 100 mg), was investigated in eight healthy young men in a double-blind placebo crossover design. The unmasking conditions of a shortened constant-routine protocol (mini-CR) were used to collect evening phase markers of physiological parameters. In comparison to placebo, all three drug administrations induced an earlier dim-light melatonin onset (DLMO), an earlier increase in distal skin temperature, and an earlier decrease in core body temperature (CBT), heart rate, and proximal skin temperature. This indicates that administration at 18 h of both melatonin and S-20098 (more pronounced with 100 than 5 mg) induced an earlier regulation of the endogenous circadian nocturnal decline in CBT. On the posttreatment day a second mini-CR revealed persistent significantly phase-advanced circadian rhythms as estimated by DLMO, as well as by the midrange crossing time of CBT and heart rate decline. There were no significant differences between the two doses of S-20098. The data suggest that, in addition to immediate thermoregulatory changes, a phase advance of the circadian system had occurred and that the phase advance could still be measured on the posttreatment day.
Cardiovascular response to stress: baroreflex resetting and hemodynamics
Authors: Hatton D. C. , Brooks V. , Qi Y. , McCarron D. A.
Published: December 2017

Borderline hypertensive rats (BHR) were used to test the hypothesis that baroreflex resetting prevents a fall in blood pressure (BP) when cardiac output (CO) is reduced during air-jet stress. Eight-week-old BHR were instrumented with flow probes around the ascending aorta for measuring CO, femoral and jugular catheters were inserted for measurement of arterial pressure and infusion of drugs, and sinoaortic baroreceptors were either denervated (SAD) or left intact. Alternating bolus injections of phenylephrine and sodium nitroprusside were given at baseline and during air-jet stress to assess the baroreflex. Air-jet stress immediately shifted the midpoint of the baroreflex curve for heart rate (HR) to a higher BP levels. When metoprolol was administered during air-jet stress, HR was reduced and CO reverted to prestress levels, but the stress-induced pressor response was not changed. In SAD BHR, air-jet stress caused an elevation of BP that was not different from intact rats. Administration of metoprolol to SAD rats during air-jet stress resulted in a further elevation rather than a reduction in BP. We conclude that the sinoaortic cardiac baroreflex is reset during air-jet stress and that it integrates reflex changes in BP during stress. The arterial baroreflex is not, however, necessary for the initiation or maintenance of the pressor response during stress, nor does it prevent a fall in BP when CO is compromised during stress.
Canine adrenal catecholamine response to VIP is blocked by PACAP-(6-27) in vivo
Authors: Gaspo R. , Lamarche L. , de Champlain J. , Yamaguchi N.
Published: December 2017

The goal of the present study was to characterize the adrenal catecholamine response to exogenous vasoactive intestinal peptide (VIP) in anesthetized dogs. We studied the potential involvement of mechanism(s) mediated by muscarinic receptors, L-type Ca2+ channels, VIP-ergic receptors, or pituitary adenylate cyclase-activating peptide (PACAP) receptors. The study consisted of five groups: a vehicle control group receiving VIP (5 micrograms) in the presence of saline and four drug-treated groups receiving VIP (5 micrograms) in the presence of either atropine (500 micrograms), nifedipine (50 micrograms), [Lys1,Pro2,5,Arg3,4,Tyr6]VIP (50 micrograms), or PACAP-(6-27) (50 micrograms). All drugs were locally infused to the left adrenal gland. Plasma catecholamine concentrations were measured in adrenal venous and aortic blood by a high-pressure liquid chromatography-electrochemical method. In the control group, VIP produced a significant increase in adrenal catecholamine output. Neither atropine, nifedipine, nor[Lys1,Pro2,5,Arg3,4,Tyr6]-VIP significantly affected the medullary response to VIP. In the presence of PACAP-(6-27), however, the catecholamine response to VIP was attenuated by approximately 77% (P < 0.05). The present study suggests that adrenal catecholamine secretion induced by exogenous VIP may be mediated by a PACAP-related mechanism, most probably through a PACAP type I receptor, in anesthetized dogs. The data also indicate that neither muscarinic receptors, VIP-ergic receptors, nor dihydropyridine-sensitive L-type Ca2+ channels are operative in the adrenal catecholamine response to exogenous VIP in vivo.
Measurement of NO synthesis in humans by L-[15N2]arginine: application to the response to vaccination
Authors: Macallan D. C. , Smith L. M. , Ferber J. , Milne E. , Griffin G. E. , Benjamin N. , McNurlan M. A.
Published: December 2017

Induction of nitric oxide (NO) synthesis is a key element of the inflammatory response in humans. We describe a sensitive gas isotope ratio mass spectrometric (GIRMS) method for measuring urinary [15N]nitrate production during intravenous infusion of L-[guanidino-15N2]arginine and its application to investigate the effects of a controlled inflammatory stimulus, typhoid vaccination, on NO synthesis in humans. Intravenous infusion of L-[15N2]arginine at 5-12 mumol.kg-1.h-1 for 24 h in three subjects was used to determine arginine and nitrate pool kinetics. Eight subjects received primed constant infusion of 2.5 mumol.kg-1.h-1 of L-[15N2]arginine for 12 h once before and again after typhoid vaccination. NO synthesis was calculated from 15N enrichment of plasma arginine and urinary nitrate, measured by gas chromatography mass spectrometry and GIRMS, respectively, and total urinary nitrate excretion. Baseline NO synthesis was 298 +/- 44 nmol.h-1.kg lean body mass-1, representing 0.41% of arginine flux. After vaccination, NO synthesis (267 +/- 77 nmol.h-1.kg-1) was not increased (P = 0.18), despite demonstration of an acute phase response. Typhoid vaccination is not accompanied by accelerated NO synthesis.
Characteristics of renal Na(+)-D-glucose cotransport in the skate (Raja erinacea) and shark (Squalus acanthias)
Authors: Kipp H. , Kinne-Saffran E. , Bevan C. , Kinne R. K.
Published: December 2017

We have investigated the properties of the skate (Raja erinacea) and shark (Squalus acanthias) kidney Na(+)-D-glucose cotransporters (SGLT) in uptake studies of radiolabeled substrates into isolated renal brush-border membrane vesicles (BBMV). Scatchard plot analysis of the substrate dependence revealed that the Na(+)-D-glucose cotransporter population is homogenous within each species. Skate BBMV showed a relatively high affinity for D-glucose [Michaelis constant (K(m)) = 0.12 mM] with an apparent coupling ratio of approximately 2 Na+ to 1 D-glucose, whereas the shark transporter was much lower in affinity (K(m) = 1.90 mM) and had a lower coupling ratio, more like 1 Na+ to 1 D-glucose. These characteristics resemble the properties of SGLT1 and SGLT2, which are known to coexist in the mammalian kidney. Inhibitor studies using sugar analogs and glucosides suggested structural differences of the D-glucose binding site among these transporters, whereas the hydrophobic transporter domains in the vicinity of the D-glucose binding site appeared to be similar. In the high-affinity skate system, D-glucose was recognized by hydrogen bonds to the hydroxy groups at C-2, C-3, and C-4 and by hydrophobic interaction with the C-6 methylene group. In contrast, the low-affinity shark system seemed to lack the hydrophobic recognition motif for the C-6 methylene group of D-glucose.
Vasopressin and V1-receptor antagonists modulate the activity of NTS neurons receiving baroreceptor input
Authors: Hegarty A. A. , Felder R. B.
Published: December 2017

Arginine vasopressin (AVP) may act as a neurotransmitter or neuromodulator in the solitary tract nucleus (NTS). To determine whether AVP influences the activity of NTS neurons receiving cardiovascular afferent input, we used single-unit extracellular recording combined with local microinjection to test the effects of AVP and V1-receptor antagonists (antAVP) on spontaneously active NTS neurons in anesthetized rats. Phenylephrine-induced increases in arterial pressure were used to identify neurons receiving baroreceptor input. Phenylbiguanide was used to stimulate chemosensitive cardiopulmonary receptors. AVP excited 31 of 81 NTS neurons tested and inhibited 15 of 81 neurons. AntAVP had independent effects on NTS neurons: in addition to blocking the effects of AVP, antAVP inhibited 26 of 72 neurons but excited only 13. Eighty-two percent of NTS neurons receiving excitatory or inhibitory baroreceptor inputs responded to AVP; 61% of these were excited by AVP. Fifty-eight percent of neurons receiving cardiopulmonary receptor input responded to AVP. These results suggest that AVP in rat NTS has a tonic, predominantly excitatory influence on a significant proportion of baroreceptor-related neurons.
Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin
Authors: Lang C. H. , Pollard V. , Fan J. , Traber L. D. , Traber D. L. , Frost R. A. , Gelato M. C. , Prough D. S.
Published: December 2017

The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection.
Intraportal mercaptoacetate infusion increases afferent activity in the common hepatic vagus branch of the rat
Authors: Lutz T. A. , Diener M. , Scharrer E.
Published: December 2017

Because dissection of the common hepatic vagus branch attenuated the feeding response to intraperitoneal injection of mercaptoacetate (MA), an inhibitor of fatty acid oxidation, in rats fed a fat-enriched diet (18% fat), the effect of MA on the discharge rate in afferents of the common hepatic vagus branch was investigated. Intraportal infusion of the Na salt of MA (200, 400, and 800 mumol/kg) in rats adapted to the 18% fat diet dose dependently increased the discharge rate in afferents of the common hepatic vagus branch, whereas NaCl and the Na salt of the structurally related compound 2-mercaptopropionate had no effect. The lowest dose of MA yielding a significant increase in the discharge rate was 400 mumol/kg. This agrees with the dose dependence of the feeding response to MA. These findings are consistent with the notion that hepatic fatty acid oxidation controls food intake by modulating the discharge rate of vagal afferents.
Protein-induced increase in urinary dopamine in normal and diabetic rats: role of catecholamine precursors
Authors: Muhlbauer B. , Mickeler C. , Schenk F.
Published: December 2017

Feeding and protein intake increase renal dopamine excretion (UDAV). Here the contribution of amino acids (AA), L-tyrosine (Tyr), and L-phenylalanine (Phe) to UDAV in conscious normal rats and in animals with streptozotocin (STZ)-induced (60 mg/kg) diabetes mellitus was investigated. Feeding a standard chow (17.3% protein) increased UDAV in normal rats over twofold compared with the fasted state, but the effect was completely abolished by feeding a low-protein (LP, 0.03%) diet. In STZ rats, UDAV was equal to that of normal rats during the fasted periods but was higher in fed animals, resulting most likely from the higher protein intake of STZ rats. In another series, rats on LP diet were given AA solutions (7, 14, and 21 g.kg-1.24 h-1) by gastric tube, which dose dependently increased UDAV to 67.3 +/- 4.3, 91.1 +/- 5.0, and 129 +/- 17 nmol.kg-1.day-1, respectively, compared with tap water as vehicle control (H2O, 55.6 +/- 7.0 nmol.kg-1.day-1). In rats kept without access to chow, administration of AA including Phe and Tyr (AAPT) increased UDAV twofold compared with H2O, whereas AA solution without Tyr and Phe did not change UDAV. Tyr or Phe alone increased UDAV to the same extent as observed in AAPT. Higher doses of Tyr further increased UDAV dose dependently but with saturation characteristics. UDAV of the animals that were in a slightly negative sodium balance was not correlated to renal sodium excretion. It is concluded that, in conscious rats, the increase in UDAV in response to feeding 1) depends on the supply of catecholamine precursors solely, 2) is dose dependent and saturable, and 3) is not affected by experimental diabetes mellitus.
Regulation of angiotensin II AT1 and AT2 receptors in neonatal ureteral obstruction
Authors: Yoo K. H. , Norwood V. F. , el-Dahr S. S. , Yosipiv I. , Chevalier R. L.
Published: December 2017

Chronic unilateral ureteral obstruction (UUO) in early development activates the intrarenal renin-angiotensin system and leads to profound renal vasoconstriction, renal growth arrest, and interstitial fibrosis. To investigate the response of the AT1 and AT2 subtypes of the angiotensin II (ANG II) receptors to UUO, Sprague-Dawley rats underwent UUO or control sham operation in the first 48 h of life and were studied 1-28 days later. Renal mRNA for renin, AT1 and AT2 receptor, and receptor binding and distribution were determined. In contrast to controls, renin mRNA increased from 14 to 28 days in the obstructed kidney. After ipsilateral UUO, AT1 mRNA was suppressed at 1 day, but had increased compared with controls at 28 days. AT2 receptor mRNA fell rapidly in all kidneys from 1 to 3 days of age, after which it remained undetectable. Compared with the intact opposite kidney, AT2 mRNA was suppressed in the obstructed kidney 1 day after UUO. Compared with controls, AT1 and AT2 receptor binding was decreased by ipsilateral UUO at 1 day, whereas AT1 binding was increased at 28 days. Renal ANG II content was increased in the obstructed compared with the intact opposite kidney 28 days after UUO. In view of the increase in renal renin and angiotensin II production resulting from UUO, increased renal AT1 mRNA and receptor binding are likely to contribute to the vasoconstriction and interstitial fibrosis of the neonatal kidney after prolonged UUO.
Effect of angiotensin II receptor blockade on proximal tubular fluid reabsorption
Authors: Leyssac P. P. , Karlsen F. M. , Holstein-Rathlou N. H.
Published: December 2017

The effect of physiological concentrations of angiotensin II on proximal tubular fluid reabsorption remains controversial. To investigate the effect of blockade of intratubular AT1 receptors on tubular reabsorption, losartan (10(-5) M) was administered by microperfusion into an early proximal convolution of halothane-anesthetized Sprague-Dawley rats. Four parameters that depend on the rate of proximal fluid reabsorption were measured: proximal intratubular pressure (Pprox), early and late proximal flow rate, and early distal NaCl concentration. Pprox decreased by 0.5 +/- 0.1 mmHg, late proximal flow rate decreased by 2.0 +/- 0.8 nl/min, and early distal NaCl concentration decreased by 4.3 +/- 0.8 mM (mean +/- SE). No changes were observed after microperfusion with saline. Because the tubuloglomerular feedback mechanism was operating in the closed-loop mode, the decreased NaCl load to the macula densa will be compensated by an increase in the single-nephron glomerular filtration rate. In agreement with this, the early proximal flow rate, measured proximal to the site of losartan administration, increased by 5.7 +/- 1.3 nl/min. The increase in the rate of proximal reabsorption between the early and late proximal convolutions was estimated to be 7.8 nl/min (approximately 36%). It is concluded that a decrease in local luminal angiotensin II levels and/or AT1 receptor activity under free flow conditions increases the rate of proximal tubular fluid reabsorption.
Polyethylene glycol-induced calcium appetite
Authors: Tordoff M. G.
Published: December 2017

Polyethylene glycol (PEG) has been used to investigate the physiological basis of sodium intake because it sequesters sodium from the extracellular fluid (ECF) and causes rats to drink concentrated NaCl solutions. To test the hypothesis that PEG also depletes ECF calcium and thus activates calcium intake, male Sprague-Dawley rats received two-bottle tests with a choice between a taste solution and water. Relative to intakes after control injections, rats injected with PEG (5 ml of 30% wt/wt sc) drank significantly greater volumes of several calcium solutions (0.1, 1, 10, or 32 mM CaCl2 or 10 or 100 mM calcium lactate). They also drank more 10 mM SrCl2, 300 mM NaCl, and 100 mM KHCO3, drank less 10 mM sodium saccharin, and did not alter intakes of 10 or 100 mM KCl, 32 mM NH4Cl, 10 mM AlCl3, 10 mM FeCl2, 100 mM CaCl2, or 1,000 mM NaCl. Thus PEG treatment produced an appetite that was specific to low and moderate concentrations of calcium, sodium, and perhaps bicarbonate. The physiological basis for this appetite was explored. At 24 h after PEG injection, plasma total calcium concentrations were either unaltered or increased, but plasma ionized calcium concentrations were reduced. Concentrations of parathyroid hormone and calcitonin but not 1 alpha, 25-dihydroxyvitamin D3 were elevated. Perhaps one or more of these changes in calcium homeostasis is responsible for the increased calcium intake. Whatever the mechanism, it is clear that PEG treatment induces an appetite for calcium in addition to the well-known appetite for sodium.
Effect of hypothyroidism on adenylyl cyclase activity and subtype gene expression in brown adipose tissue
Authors: Chaudhry A. , Granneman J. G.
Published: December 2017

Brown adipose tissue (BAT) expresses several adenylyl cyclase (AC) subtypes, and adrenergic stimulation selectively upregulates AC-III gene expression. Previous studies have described synergistic interactions between the sympathetic nervous system (SNS) and 3,5,3'-triiodothyronine (T3) on the regulation of gene expression in BAT. Because adrenergic stimulation also increases the activity of BAT type II thyroxine 5'-deiodinase (DII) and local T3 generation is important for many functional responses in BAT, we examined the effects of thyroid hormone status on the expression of various AC subtypes. Hypothyroidism selectively increased AC-III mRNA levels in BAT but not in white adipose tissue. Of the other subtypes examined, hypothyroidism did not alter AC-VI mRNA levels and slightly reduced AC-IX mRNA levels in BAT. The increase in AC-III expression was paralleled by an increase in forskolin-stimulated AC activity in BAT membranes. Sympathetic denervation of BAT abolished the increase in both AC activity and AC-III mRNA expression produced by hypothyroidism, but did not affect the expression of other subtypes. Surgical denervation also prevented the induction of AC-III in the cold-stressed euthyroid rat, but injections of T3 failed to alter AC-III expression in intact or denervated BAT. Our results indicate that T3 does not directly affect expression of AC-III. Rather, hypothyroidism increases BAT AC-III expression indirectly via an increase in sympathetic stimulation. Furthermore, our results strongly indicate that the increase in AC activity in hypothyroid BAT is due to increased expression of AC-III.
Improved body composition after 8 wk of electrically stimulated leg cycling in tetraplegic patients
Authors: Hjeltnes N. , Aksnes A. K. , Birkeland K. I. , Johansen J. , Lannem A. , Wallberg-Henriksson H.
Published: December 2017

The practical aspects of utilizing electrically stimulated leg cycling (ESLC) to counteract alterations in body composition were investigated in five tetraplegic subjects with long-standing complete spinal cord injuries (C5-C7). After a 2-wk adaptation period, the subjects performed seven ESLC sessions per week for 8 wk. No adverse reactions were noted in response to the ESLC program. The ESLC sessions were accompanied by higher lactate concentrations compared with arm exercise. Heart rate and blood pressure response revealed clear, but not serious, signs of autonomic dysreflexia in the beginning of the ESLC sessions. Body temperature increased moderately during the ESLC sessions. Peak oxygen uptake (Vo2) during an ESLC session increased by 70% (P < 0.05) after 8 wk of training. Body composition, evaluated by dual-energy X-ray absorptiometry (DEXA), demonstrated an increase in lean body mass (LBM) from 66.2 +/- 2.6 to 68.2 +/- 2.1% (P < 0.05), with a concomitant decrease in whole body fat (BF) content from 29.7 +/- 2.6 to 27.8 +/- 2.1% (P < 0.05) after training. The cross-sectional area of quadriceps, hamstrings, gluteus maximus, and gluteus medius muscles, measured by computer tomographic scans, increased from 267 +/- 27 to 324 +/- 27 cm2 (P < 0.05) after the training. In conclusion, daily ESLC sessions during a 2-mo period resulted in increased LBM, decreased BF content, and increased muscular endurance in tetraplegic subjects without any noticeable adverse effects.
Satiety from fat? Adverse effects of intestinal infusion of sodium oleate
Authors: Ramirez Israel , Tordoff Michael G. , Friedman Mark I.
Published: December 2017

To determine whether damage to the intestinal mucosa by oleic acid causes the suppression of food intake observed in response to intraintestinal infusion of the fatty acid, we measured lactate dehydrogenase (LDH) activity, a marker for cell damage, in the intestinal lumen after intestinal infusion of fatty acid under conditions similar to those employed in studies of eating behavior. Infusions of 25 or 51 mM sodium oleate (neutralized oleic acid) markedly and rapidly increased LDH activity, whereas infusions of saline had little or no effect. Infusion of octanoate, which has been reported to be ineffective in reducing eating behavior, did not increase intestinal LDH activity relative to saline infusion. Similarly, infusion of ethyl oleate or free (nonneutralized) oleic acid neither increased luminal LDH activity nor suppressed food intake. Infusion of sodium oleate also produced a strong conditioned aversion to sucrose. The results strongly suggest that the suppression of food intake induced by intraintestinal infusion of sodium oleate is due to the injurious effects of this unphysiological form of the fatty acid.
Tannic acid elicits neurogenic plasma exudation from the in situ hamster cheek pouch
Authors: Gao Xiao-Pei
Published: December 2017

The purpose of this study was to determine whether tannic acid elicits neurogenic plasma exudation from the oral mucosa in vivo and, if so, whether this response is transduced in part by thel-arginine-nitric oxide (NO) biosynthetic pathway. Using intravital microscopy, we found that suffusion of tannic acid elicits significant concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-dextran (molecular mass 70 kDa) from the in situ hamster cheek pouch ( P < 0.05). These effects are significantly attenuated by two selective, but structurally distinct, nonpeptide neurokinin-1 (NK1) receptor antagonists, CP-96,345 and RP-67580, but not by CP-96,344, the 2R,3R enantiomer of CP-96,345. N G-nitrol-arginine methyl ester (l-NAME), an NO synthase inhibitor, but notd-NAME, significantly attenuates tannic acid-induced responses.l-Arginine, but notd-arginine, reverses the attenuating effects of l-NAME. We conclude that tannic acid elicitsl-arginine-NO biosynthetic pathway-dependent neurogenic plasma exudation from the in situ hamster cheek pouch.
Load-sensitive rat gastric vagal afferents encode volume but not gastric nutrients
Authors: Mathis Carole , Moran Timothy H. , Schwartz Gary J.
Published: December 2017

To assess nutrient sensitivity in a population of gastric load-sensitive vagal afferents, their neurophysiological activity was examined in anesthetized rats with inflated pyloric cuffs after gastric infusion of a range of volumes of nutrient and equiosmotic saline solutions. Responses to physiological saline loads (1, 2, 4, and 8 ml) were compared with responses elicited by the same volume range of carbohydrate (12.5% glucose), protein (12.5% peptone), and equiosmotic hypertonic (750 mosM) saline. The threshold load volume of physiological saline required to increase gastric vagal afferent activity was 1 ml. Thereafter, there was a dose-dependent relationship between increasing gastric volume and firing rate and between gastric volume and pressure. The dose-response relationships elicited by glucose, peptone, and equiosmotic hypertonic saline loads did not differ from those elicited by physiological saline loads. These data identify a population of gastric load-sensitive vagal afferents unresponsive to the chemical composition of gastric contents and are consistent with a role for vagal gastric volume signals but not gastric nutrient content in the negative feedback control of ingestion.