bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence against nonprostanoid endothelium-derived relaxing factor(s) in trout vessels
Authors: Olson K. R. , Villa J.
Published: December 2017

Bradykinin (BK)- or acetylcholine (ACh)-mediated vasodilation has only rarely been observed in fish. This suggests that many fish vessels lack the endothelium-dependent relaxing mechanisms recently identified in mammals. To examine this hypothesis, isolated vascular rings were prepared from trout ventral aortas (VA), efferent branchial and celiacomesenteric (CM) arteries, and anterior cardinal veins (CV) and examined for endothelium-mediated responses. A doubly perfused trunk preparation was also used to evaluate the response of the microcirculation. ACh produced dose-dependent contractions in all vascular rings and increased vascular resistance when perfused into the CM but had no affect when perfused into the dorsal aorta. Neither ACh nor BK relaxed precontracted vessels or lowered resting tone. Removal of the endothelium did not affect ACh or BK responses. The calcium ionophore A23187 produced an endothelium-dependent relaxation of precontracted VA, CM, and CV. The A23187 response was abolished by indomethacin, indicating that a prostanoid was involved in the relaxation. ATP contracted and/or relaxed precontracted CM and CV. ATP effects were independent of an intact endothelium. Sodium nitroprusside and atrial natriuretic factor partially or completely relaxed all vessels, indicating the presence of soluble and particulate guanylate cyclases, respectively. These results suggest that nonprostanoid endothelium-derived relaxing factors (EDRFs) or EDRF-like vasodilator mechanisms are not present in trout vessels or, if they are, they are not released by classical agonists.
Tracer norepinephrine kinetics: dependence on regional blood flow and the site of infusion
Authors: Grossman E. , Chang P. C. , Hoffman A. , Tamrat M. , Kopin I. J. , Goldstein D. S.
Published: December 2017

The rate of appearance of the sympathetic neurotransmitter norepinephrine (NE) in the regional venous drainage (NE spillover) can be estimated based on intravenous or intra-arterial infusions of [3H]NE. The present study examined whether forearm NE spillover (FASO) in humans depends on forearm blood flow (FBF) and on the site of infusion of the tracer. Healthy volunteers underwent infusions of [3H]NE and [3H]isoproterenol (Iso) administered intravenously (n = 21), intra-arterially (n = 32), or by both routes in the same experimental session (n = 7). FBF was manipulated by intra-arterial infusions of the vasodilator sodium nitroprusside (n = 7) or the vasoconstrictor methoxamine (n = 7). Forearm extraction percents of [3H]NE exceeded those of [3H]Iso in all subjects undergoing intravenous infusions (54 vs. 46%, P less than 0.001), whereas extraction percents of [3H]Iso exceeded those of [3H]NE when the tracers were infused intra-arterially. Regardless of the infusion site, FASO was positively correlated with FBF (r = 0.44, P less than 0.005). Nitroprusside increased FBF and FASO, and methoxamine decreased FBF and FASO. When the tracers were added to whole blood, 89% of [3H]NE and 83% of [3H]Iso remained in plasma after 1 min; although no further loss of [3H]NE occurred over time, only 60% of the added [3H]Iso remained in plasma by 20 min. The results indicate that regional NE spillover is flow dependent, complicating inferences about regional sympathoneural activity. Intra-arterial infusion of [3H]NE results in higher estimates of regional NE spillover than does intravenous infusion of the tracer.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolic actions of morphine in conscious chronically instrumented pigs
Authors: Bossone C. A. , Hannon J. P.
Published: December 2017

Effects of a modest dose of morphine sulfate (1 mg/kg) on total body energy metabolism, body thermal status, and the plasma concentrations of certain electrolytes and metabolites were investigated in conscious chronically instrumented pigs (n = 8). Control pigs (n = 8) received an equivalent volume of normal saline. Intravenous morphine injection led to an excitatory state associated with significant (P less than or equal to 0.05) immediate increases in O2 consumption. CO2 production, respiratory exchange ratio, and plasma concentrations of lactate, glucose, potassium, phosphate, epinephrine, and norepinephrine. Significant more gradual increases were observed in rectal and skin temperatures, body heat content, and the plasma concentrations of adrenocorticotropic hormone, cortisol, and phosphate. The hypermetabolic state persisted for approximately 1 h. Thereafter, most functional variables regressed toward, but did not reach, control levels. Increased muscle activity appeared to be the major factor underlying the rise in energy metabolism. Body heat storage after morphine injection appeared to be attributable to increased heat production coupled with an inadequate rise in heat loss.
Central nervous system norepinephrine release during hypotension and hyperosmolality in conscious rats
Authors: Van Huysse J. W. , Bealer S. L.
Published: December 2017

Extracellular norepinephrine (NE) levels in the paraventricular/anterior hypothalamic area (P/A) and in the dorsomedial medulla (DM) in conscious Sprague-Dawley rats were estimated by in vivo microdialysis before, during, and after sustained hypotension (75 mmHg mean arterial pressure) produced either by hemorrhage (Hem) or by 2-chloroadenosine infusion (2-Cl-ADO, 2.6-26.0 micrograms/min iv). P/A and DM NE were also measured before, during, and after hypertonic saline infusion (HTS; 1.5 M NaCl at 10 microliters.100 g-1.min-1 iv). P/A and DM NE increased during both Hem and 2-Cl-ADO and returned to baseline after reinfusion of hemorrhaged blood or after 2-Cl-ADO was stopped. However, Hem caused greater increases in P/A NE than 2-Cl-ADO despite equivalent decreases in blood pressure. Hem and 2-Cl-ADO produced equivalent changes in DM NE. HTS did not change P/A or DM NE despite increases in blood pressure of approximately 15 mmHg and plasma osmolality of approximately 30 mosmol/kgH2O. We conclude that 1) hypotension increases P/A and DM NE, which may mediate compensatory responses, 2) Hem is a more potent stimulus for NE release in the P/A than isovolemic hypotension induced by 2-Cl-ADO, and 3) the hypertensive response to HTS does not involve changes in P/A or DM NE.
Sodium appetite in rats after prolonged dietary sodium deprivation: a sexually dimorphic phenomenon
Authors: Stricker E. M. , Thiels E. , Verbalis J. G.
Published: December 2017

Little sodium appetite is observed when rats are deprived of dietary sodium for several days, presumably because aldosterone secretion minimizes renal sodium losses. However, the present studies indicate that when sodium deprivation is extended to 8 days, a spontaneous sodium appetite results that far exceeds urinary sodium losses during the deprivation period; indeed, adult male rats drank as much 0.5 M NaCl solution as rats ever have been reported to drink rapidly. In contrast, female rats drank much less saline after 8 days of sodium deprivation. Because of this sexual dimorphism in sodium appetite, we also studied NaCl intake in gonadectomized rats after 8 days of sodium deprivation. Both male and female gonadectomized rats drank comparable amounts of saline as intact male rats, but they consumed much less when treated with physiological amounts of estrogen during the sodium-deprivation period. These results indicate that a robust appetite for NaCl can be produced in rats by prolonged sodium deprivation and that estrogen can blunt the induced sodium appetite.
Resumption of physiological functions in the wood frog (Rana sylvatica) after freezing
Authors: Layne J. R. , First M. C.
Published: December 2017

We monitored the resumption of physiological functions in frogs that were frozen at -2 to -3 degrees C for 24 h and thawed rapidly (at 23-25 degrees C) or slowly (at 6-8 degrees C). Bodily functions were restored sooner during fast thawing, but this did not enhance the survival of frogs. The first physiological parameter to return was cardiac function, but during the early stages of thawing heart rates were lower than heart rates of unfrozen frogs at comparable body temperatures. Heart rates increased thereafter in conjunction with the rise in frog body temperatures. Spontaneous breathing and hindleg reflexes resumed after cardiac function, but neither response was exhibited by all frogs after the conclusion of the observation periods (3-4 h). Finally, isolated gastrocnemius muscles that had undergone in vitro freezing showed no significant (P greater than 0.05) impairment of twitch and tetanic tensions even as soon as 1 h after the onset of thawing. Body systems thus vary in their rates of recovery after nonlethal freezing episodes. Furthermore, recovery of specific body systems corresponds to essential needs that must be met immediately after thawing, such as reperfusion of body tissues.
Renal, hormonal, and fluid shift responses to ANP during head-out water immersion in awake dogs
Authors: Krasney J. A. , Carroll M. , Krasney E. , Iwamoto J. , Claybaugh J. R. , Hong S. K.
Published: December 2017

Renal responses to low doses of atrial natriuretic peptide (ANP) may be potentiated during water immersion-induced central hypervolemia. To test this hypothesis, ANP was infused in awake dogs in doses of 0, 5, and 25 ng.kg-1.min-1 either when the dogs were in air or during head-out water immersion (WI) under thermoneutral conditions (37 degrees C). In general, there were greater diuretic (V) and natriuretic responses (UNaV) at the same level of plasma ANP in WI, with the slopes (or sensitivities) of V and UNaV in relation to plasma ANP levels being significantly increased during WI. Plasma renin activity decreased only during WI and was significantly correlated with both V and UNaV only during WI. Plasma and urinary arginine vasopressin levels were unchanged during WI. Infusion of ANP prevented the usual decline of hematocrit that occurs during WI. These results support the view that the renal sensitivity to ANP is augmented during the plasma volume expansion of WI. In addition, ANP may attenuate the transcapillary fluid shift that occurs during WI.
Sympathetic nerve activity and renal responses during continuous negative-pressure breathing in humans
Authors: Tanaka H. , Sagawa S. , Miki K. , Tajima F. , Freund B. J. , Claybaugh J. R. , Shiraki K.
Published: December 2017

A stretch stimulus of the cardiopulmonary receptors results in a diuresis and natriuresis in dogs due to a suppression of renal sympathetic nerve activity. In the present experiment, the stretch stimulus in humans was given by means of continuous negative-pressure breathing (CNPB), and muscle sympathetic nerve activity (MSNA), renal responses, and hormones were measured to examine whether MSNA response during CNPB correlated with the usual renal and hormonal responses for stretch stimulus of the cardiopulmonary receptors. Nine healthy males were subjected to CNPB at -11 mmHg for 60 min. MSNA in the peroneal muscle nerve fascicles was measured continuously before (pre-CNPB), during, and after CNPB (post-CNPB). A step and sustained decrease (P less than 0.05) in MSNA (30 +/- 6% for burst frequency and 37 +/- 4% for total activity from pre-CNPB level) was observed during CNPB and it returned to pre-CNPB level at post-CNPB. Urinary excretion increased by 58 +/- 18% (P less than 0.05) during CNPB, and the diuresis was entirely osmolal in nature because of a significant increase (P less than 0.05) in Na excretion and a constant free-water clearance. The plasma level of norepinephrine decreased significantly (P less than 0.05) during CNPB and remained decreased (P less than 0.05) at post-CNPB. A twofold increase (P less than 0.05) in plasma atrial natriuretic peptide and a 35 +/- 9% reduction (P less than 0.05) in plasma renin activity were observed during CNPB, whereas no change was observed in plasma aldosterone and arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
Microdialysis of norepinephrine into preoptic area of guinea pigs: characteristics of hypothermic effect
Authors: Quan N. , Xin L. , Blatteis C. M.
Published: December 2017

This study was designed to characterize the previously described hypothermic action of norepinephrine (NE) microdialyzed into the medial preoptic area (MPO) of conscious guinea pigs. To this end, the effects on core temperature (Tco) of isotonic pyrogen-free saline (PFS), hypotonic PFS, inactive (oxidized) NE (hypertonic), 5-hydroxytryptamine (5-HT, 10 and 20 micrograms/microliter), PFS with or without 2.4 mM Ca2+, 10 micrograms/microliters NE with Ca2+, and various doses of NE (0.05-60 micrograms/microliters) were compared in a series of studies at an ambient temperature (Ta) of 24 degrees C. The Tco responses to 10 micrograms/microliters NE in a cold (15 +/- 2 degrees C) and a warm (31 +/- 1 degrees C) Ta and during the night in the dark in Ta 24 degrees C were also measured. Bromophenol blue (0.2%) was microdialyzed to assess the extent of diffusion of these dialysates. A stain was found in the MPO, which increased in density but did not spread beyond this region over 3 h of continuous microdialysis. Neither PFS nor the hypotonic and hypertonic solutions had any obvious effect on Tco. Similarly, neither dose of 5-HT evoked a thermal response. Ca2+ added to either PFS or NE did not alter the usual Tco responses to these two solutions. NE induced dose-dependent hypothermia in Ta 24 degrees C. NE microdialyzed in Ta 15 degrees C also produced Tco falls, but these responses were smaller than those in 24 degrees C. NE had no effect in the warm Ta. During the night, NE elicited similar Tco falls, but their recoveries after dialysis ended were slower than during the day.(ABSTRACT TRUNCATED AT 250 WORDS)
A5 noradrenergic unit activity and sympathetic nerve discharge in rats
Authors: Huangfu D. H. , Koshiya N. , Guyenet P. G.
Published: December 2017

Unit recording experiments were designed to determine whether A5 noradrenergic neurons contribute to the generation of the splanchnic sympathetic nerve discharge (SSND) of halothane-anesthetized rats. Neurons (presumed A5 cells) were selected on the following bases: location in the ventrolateral tegmentum rostrolateral to facial nucleus (FN), antidromic (AD) activation from thoracic spinal cord, and complete inhibition by clonidine (10-15 micrograms/kg iv). These cells (n = 59) had low rates of spontaneous firing (1.4 +/- 0.2 spikes/s) and slow conduction velocities (2.6 +/- 0.2 m/s). The AD activation of seven of eight neurons was abolished within 1 h after intraspinal microinjection of 6-hydroxydopamine (4 micrograms), but the drug failed to affect the AD responses of eight sympathoexcitatory cells located caudal to the FN (control cells). The terminal fields of 16 A5 area neurons were found in the intermediolateral cell column of the spinal cord. Most neurons (63%, 37/59) were inhibited by raising arterial pressure and by train stimulation of the aortic depressor nerve (ADN, 47%, 9/20). A few cells responded to ADN stimulation but not to arterial pressure elevation or vice versa. The discharge of the cells was correlated to the SSND and preceded a peak of SSND by 69 +/- 6 ms (12/29 in intact and 3/9 in debuffered rats). We conclude that 40% of A5 cells may have a visceral vasomotor sympathoexcitatory function.
Fetal fluid responses to long-term 5 M NaCl infusion: where does all the salt go?
Authors: Powell T. L. , Brace R. A.
Published: December 2017

The fetus must obtain Na and Cl ions in order to grow. However, the regulation of electrolyte acquisition by the fetus is not well understood. To explore fetal electrolyte balance, we intravenously infused 5 M NaCl at a rate equal to 80% of the total fetal body Na+ and Cl- content per day (240 mM/day) for 3 days into late-gestation fetal sheep. We hypothesized that the increase in fetal osmolality resulting from the infusion would cause a transplacental water movement into the fetal compartment, leading to hydrops fetalis and/or polyhydramnios. The fetal-to-maternal osmotic gradient was initially -2.8 +/- 0.9 (SE) mosmol/kgH2O and rose by 4.8 +/- 1.8 mosmol/kgH2O during the infusion. Fetal plasma [Na+] and [Cl-] increased (3.0 +/- 0.4 and 5.5 +/- 0.5 meq/l, respectively), but the normal maternal-to-fetal transplacental concentration gradients for these ions were not reversed. Most of the infused Na+ (92 +/- 14%) and Cl- (82 +/- 12%) was excreted by the fetus in large volumes of hypotonic urine. Amniotic fluid osmolality and [Na+] were unchanged, but amniotic [Cl-] increased 5.7 +/- 2.4 meq/l. The amniotic plus allantoic fluid volume, as estimated by ultrasonography, was increased (43.5 +/- 14.5%) at day 2 and returned to control by day 3 of infusion. There was no fetal edema during the study or at autopsy. In light of these results, we propose a novel and somewhat complex mechanism for transplacental fluid and electrolyte movement in which placental capillary permeability increases along the length of the capillary.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal tubular function in horses during submaximal exercise
Authors: McKeever K. H. , Hinchcliff K. W. , Schmall L. M. , Muir W. W.
Published: December 2017

Exercise-induced changes in renal function were examined during steady-state submaximal treadmill exercise in six unfit mares. Horses were randomly assigned to either an exercise or parallel control (no exercise) trial on day 1 and the alternate trial 1 wk later. The mares ran on a treadmill, set at a 6 degrees incline, for 1 h at 55-60% of maximal heart rate. Exercise significantly (P less than 0.05) increased plasma osmolality, plasma [K+], urine flow (+ 45%), Na+ excretion (+ 371%), K+ excretion (+ 57%), osmotic clearance (+ 32%), Na+ clearance (+ 391%), K+ clearance (+ 33%), and fractional Na+ excretion (+ 320%) and significantly decreased plasma [Cl-], Cl- excretion (-46%), Cl- clearance (-41%), and fractional Cl- excretion (-47%). Glomerular filtration rate, fractional K+ excretion, and free water clearance did not change during exercise. Atrial natriuretic peptide increased during exercise from 11 +/- 1 pg/ml at rest to a peak of 40 +/- 9 pg/ml (264%, P less than 0.05) at 40 min. Increases in plasma renin activity (66%, P less than 0.05) were accompanied by increases in plasma aldosterone concentration (760%, P less than 0.05). Vasopressin concentration increased (P less than 0.05) steadily over the 60-min period of exercise. It was concluded that, in horses, submaximal exercise-induced increases in urine flow and sodium excretion are associated with a concurrent increase in the plasma concentration of atrial natriuretic peptide.
Hypothalamic lesions increase saline ingestion induced by injection of angiotensin II into AV3V in rats
Authors: Camargo L. A. , Saad W. A. , Renzi A. , de Luca Junior L. A. , Goncalves J. R. , Menani J. V.
Published: December 2017

Water and 3% NaCl intake were increased by the injection of 4 ng angiotensin II (ANG II) into the anteroventral third ventricle (AV3V) region of rats. Pretreatment with two specific ANG II receptor antagonists, [octanoyl-Leu8]ANG II and [Leu8]ANG II, significantly reduced ANG II-induced water and saline intake. This inhibition lasted approximately 30 min, with partial recovery at 60 min. In rats with electrolytic lesion of the bilateral ventromedial nucleus of hypothalamus (VMH), the effect of ANG II on water intake was not different from that observed in sham rats, but saline ingestion increased. In summary, the present results show that the AV3V region is an important central structure for ANG II-induced saline ingestion. Lesion of the VMH increases the response to ANG II, showing an interaction between the AV3V region and the VMH in the regulation of salt ingestion.
Dynamics of behavioral thermoregulation in the rat
Authors: Gordon C. J. , Lee K. L. , Chen T. L. , Killough P. , Ali J. S.
Published: December 2017

Past studies have found that the laboratory rat placed in a temperature gradient prefers temperatures that are markedly below its lower critical ambient temperature (LCT), whereas other rodents (e.g., mouse, hamster, and guinea pig) generally select thermal environments associated with minimal metabolic expenditure. To further study the rat's thermoregulatory behavior, a temperature gradient was designed to monitor the selected ambient temperature (STa) and motor activity (MA) of food-deprived rats of the Long-Evans (LE), Fischer 344 (F344), and Sprague-Dawley (SD) strains over a 22-h period. All three rat strains selected relatively cool STas of 21-26 degrees C during the first 1-3 h in the temperature gradient. This was followed by a gradual increase in the STa that peaked at 4 (F344) to 6 h (SD and LE) after being placed in the gradient. The LE strain had a significantly lower STa during the initial period in the gradient. There were slight decreases in the STa during the nocturnal phase in the F344 and SD strains concomitant with marked increases in MA. These results indicate that the rat requires a relatively long adjustment period in a temperature gradient before it exhibits STas that are associated with minimal metabolic expenditure. Given adequate time for accommodation, behavioral thermoregulatory responses of the rat appear to be similar to those of other rodents.
Vasopressin and oxytocin secretion in chronically hyposmolar rats
Authors: Verbalis J. G. , Dohanics J.
Published: December 2017

Neurohypophysial secretion of vasopressin (AVP) and oxytocin (OT) was studied in rats maintained under hyposmolar conditions for 10-24 days. Graded intravenous infusions of hypertonic saline solutions had no consistent effect on plasma AVP and OT levels until plasma sodium concentration ([Na+]) exceeded 130 mM, after which levels of both hormones increased as an exponential function of plasma [Na+]. Detectable increases in plasma AVP and OT began at significantly lower plasma [Na+] in hyposmolar rats than in normosmolar control rats (10.8 mM lower for AVP and 18.4 mM lower for OT). AVP and OT secretion in hyposmolar rats was also markedly blunted in response to nonosmotic stimuli, including acute and chronic hypovolemia and systemic administration of cholecystokinin. Cessation of 1-desamino-8-D-arginine vasopressin-induced antidiuresis resulted in an appropriately rapid correction of plasma [Na+] to normal levels within 24 h. Consequently, although chronic hyposmolarity caused a moderate downward resetting of the osmotic thresholds for AVP and OT secretion, it did not cause sustained deficits in osmoregulation. These results suggest that osmoreceptor activity is regulated to maintain extracellular fluid and plasma osmolality within narrow absolute ranges rather than responding to relative changes in osmolality.
Enhanced drinking after excitotoxic lesions of the parabrachial nucleus in the rat
Authors: Edwards G. L. , Johnson A. K.
Published: December 2017

Previous reports indicate the lateral parabrachial nucleus (IPBN) is important in the regulation of fluid intake. After electrolytic lesions of the IPBN, rats consume increased amounts of water when challenged with pharmacological stimuli that mimic depletion of the extracellular fluid space. Nonetheless, it is possible that neurons within the IPBN are not responsible for the overingestion of water during extracellular thirst challenges, since electrolytic lesions damage fibers of passage as well as neurons within the IPBN. Thus we used the excitatory neurotoxin ibotenic acid to lesion cell bodies within the IPBN. After recovery from surgery, water consumption by lesioned rats was significantly greater than consumption by vehicle or uninjected control rats when challenged with subcutaneous angiotensin II or isoproterenol to stimulate drinking. However, when injected with subcutaneous hypertonic saline to produce cellular dehydration, or when water deprived for 24 h, the water intake of rats with lesions was not different from the intake of control rats. Anatomical examination of the lesion sites revealed that ibotenic acid injection caused a notable loss of neurons in the IPBN with little or no damage to surrounding structures. Moreover, injection of an anterograde tracer into the dorsomedial medulla resulted in labeling of fibers that traverse the ibotenic acid lesion site. Together, these data suggest neurons within the IPBN are involved in the regulation of fluid intake, particularly challenges that involve depletion of the extracellular fluid space.
Studies on binding sites, contents, and effects of AVP in isolated bladder and urethra from rabbits and humans
Authors: Holmquist F. , Lundin S. , Larsson B. , Hedlund H. , Andersson K. E.
Published: December 2017

The binding sites, contents, and effects of arginine vasopressin (AVP) were studied in isolated bladder and urethral preparations from rabbits and humans. In all tissues, higher levels of AVP-like immunoreactivity (AVP-LI) were detected than those normally found in plasma. Radioligand membrane binding studies using [3H]AVP as the ligand revealed the existence of a single population of binding sites in the rabbit bladder, and displacement experiments indicated that the receptor was of the V1 subtype. By autoradiography, [3H]AVP binding sites in the rabbit bladder were shown to be located on both circularly and longitudinally oriented smooth muscle cells, as well as in the submucosa at the part adjacent to the urothelium. In the rabbit urethra, the binding sites were confined mainly to the circular smooth muscle layer. Neither radioligand membrane binding studies nor autoradiography revealed any specific [3H]AVP binding sites in the human bladder. AVP contracted rabbit bladder and urethral preparations concentration dependently. The contractions were inhibited by the V1-receptor selective antagonist A16 in a noncompetitive manner. However, A16 had no effects on contractions elicited by electrical-field stimulation. In preparations of the human bladder and urethra, AVP in concentrations up to 10(-5) M did not have any contractile effects. These results suggest that in the rabbit and human lower urinary tract, AVP-LI is synthesized locally and/or extracted from the circulation. It is unlikely that AVP is directly involved in the neurotransmission in these tissues, although in the rabbit bladder and urethra a modulatory role cannot be excluded.
Ontogeny of canine intrathoracic cardiac nervous system
Authors: Haddad C. , Armour J. A.
Published: December 2017

The functional cardiac innervation of 61 puppies from nine different litters (2-8 littermates), ranging in age from 1 day to 7 wk, was investigated. The efferent sympathetic nervous system exerted minimal effects on the heart of 1-day-old puppies, gradually influencing the heart more thereafter such that by 7 wk of life it was functionally mature. In contrast, efferent parasympathetic cardiac innervation was well developed at birth, maturing thereafter such that by 4-7 wk of age its capacity to modulate the heart was similar to that found in adults. The right- and left-sided efferent sympathetic and parasympathetic intrathoracic nervous systems induced similar cardiac modulation throughout this period of development. Cardiac myocyte beta-adrenergic receptors were partially functional at birth, as determined by responses elicited by supramaximal doses of the beta-agonist isoproterenol. Responses elicited by isoproterenol became greater over the following 7 wk of life, when they were found to be similar to those elicited in adults. By 1 wk of age, synaptic mechanisms in intrathoracic sympathetic ganglia involved in cardiac regulation were relatively well developed, with cardiopulmonary-cardiac reflexes present but not functionally mature at that age. It is concluded that maturation of the efferent sympathetic nervous system modulating the canine heart depends to a large extent on the ontogeny of cardiac beta-adrenergic receptors rather than the ontogeny of synapses in intrathoracic ganglia. Furthermore, even though functional cardiac efferent parasympathetic innervation is present before efferent sympathetic innervation, both reach maturity at about the same age.
Characteristics of the anion transport system in sea turtle erythrocytes
Authors: Stabenau E. K. , Vanoye C. G. , Heming T. A.
Published: December 2017

Erythrocytes of Kemp's ridley sea turtle (Lepidochelys kempi) contain a 100- to 105-kDa protein that is reactive with a monoclonal antibody to the membrane domain of human erythrocyte band 3. Based on inhibition of membrane HCO(3-)-Cl- exchange with 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), sea turtle erythrocytes were found to contain 4 x 10(6) copies of band 3 per cell. Unidirectional HCO3- transfer, specifically HCO3- out----in-Cl-in----out exchange, where subscript in----out represents transfer from inside to outside and subscript out----in represents transfer from outside to inside, was characterized by a maximal exchange rate of 1.0-1.1 nmol.cm-2.s-1, substrate affinity coefficients of 0.1-0.2 mM for HCO3- and 1.6 mM for Cl-, and an apparent inhibition constant for SITS of 0.6-1.0 microM (10 degrees C, pH 7.6). Under physiological conditions (30 degrees C, pH 7.4), the rate of net HCO3- transfer (i.e., the difference between HCO3- in----out-Cl-out----in and HCO3- out----in-Cl-in----out) was 1.13 nmol. cm-2.s-1 for cells subjected to a 5-mM decrement in CO2 content. This yields a rate coefficient for the "physiological" anion shift in sea turtle blood of 1.7 s-1, indicating that the anion shift may require 2.6 s to reach 99% completion in vivo. The erythrocyte anion shift appears to be a potential rate-limiting step for capillary CO2 exchange in these turtles.
Intraruminal rehydration of ovine fetuses
Authors: Ross M. G. , Sherman D. J. , Ervin M. G. , Day L.
Published: December 2017

During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water.
Effect of desipramine on norepinephrine metabolism in humans: interaction with aging
Authors: Stromberg J. S. , Linares O. A. , Supiano M. A. , Smith M. J. , Foster A. H. , Halter J. B.
Published: December 2017

To determine whether differences in neuronal reuptake contribute to age-related changes of sympathetic nervous system activity, we compared norepinephrine (NE) release and metabolism during [3H]NE infusion and decay in six young (age 19-26 yr) and seven older (age 61-73 yr) healthy nonobese subjects. Subjects were studied on a control day and on a separate day after desipramine (DMI; 125 mg orally), a neuronal reuptake blocker. Compartmental analysis of plasma NE specific activity was used to determine several NE kinetic parameters. Plasma NE levels and NE spillover rates were higher in the elderly. Although plasma NE was unaffected by DMI in both age groups, both the metabolic clearance rate of NE from plasma and the rate of NE spillover into plasma fell in young and older groups during DMI. Furthermore, DMI dramatically lowered the mass of NE in the extravascular compartment and the rate of NE entry into the extravascular compartment. Thus neuronal uptake blockade has major effects on NE release as well as NE metabolism in humans. However, age-related differences in NE kinetics cannot be explained by differences in neuronal uptake.
alpha-Chloralose alters autonomic reflex function of the lower urinary tract
Authors: Rudy D. C. , Downie J. W. , McAndrew J. D.
Published: December 2017

The effects of alpha-chloralose on the micturition reflex were evaluated using an efficiently voiding decerebrate cat model. At laparotomy cannulas were introduced into the urethra and/or bladder for measurement of urethral perfusion pressure and/or bladder pressure during bladder filling and voiding. After establishment of efficient voiding in the anesthetic-free decerebrate cat, chloralose, 50 mg/kg iv, was administered. Parameters assessed before and after anesthetic included bladder pressure at peak of contraction (voiding pressure), intravesical pressure at onset of bladder contraction (threshold pressure), contraction amplitude, duration of bladder contraction, bladder volume at onset of bladder contraction (volume threshold), and residual bladder volume after voiding (postvoid residual). In addition to these parameters, preparations with intact bladder-urethra and with divided bladder-urethra were used to assess effects of chloralose on voiding efficiency and coordination between bladder and urethra, respectively. Chloralose significantly reduced voiding pressure, contraction amplitude, and voiding efficiency. Neither vehicle for the chloralose nor sympathetic denervation of the lower urinary tract affected these reductions. Chloralose had no effect on direct contraction of the bladder and urethra produced by intra-arterial acetylcholine (25-100 micrograms). Chloralose converted the synergic bladder and urethral responses during voiding to dyssynergic responses. Neuromuscular blockade with gallamine, 10 mg/kg iv, improved voiding efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
Carbachol induces granular cell exocytosis and serotonin release in rabbit cerebral arteries
Authors: Reynier-Rebuffel A. M. , Callebert J. , Dimitriadou V. , Mathiau P. , Launay J. M. , Seylaz J. , Aubineau P.
Published: December 2017

Previously, we reported that rabbit cerebral arteries contain mast cells that frequently establish close contacts with parasympathetic-like nerve fibers. Here we have examined the possible function of this link by comparing the effects of carbachol and compound 48/80 on mast cell morphology and on the serotonin (5-HT) and histamine content of these arteries. In vivo, 2 micrograms/min of compound 48/80 or 1 micrograms/min of carbachol was infused for 30 min into one internal carotid artery of pentobarbital anesthetized rabbits, the contralateral artery being infused with vehicle. In vitro, the action of 10(-6) M carbachol was tested on isolated middle cerebral artery trees (MCAs) in the presence or absence of 10(-7) M atropine. The effects of carbachol were also tested in vitro on sympathectomized arteries. The 5-HT and histamine contents of all MCAs were measured by radioenzymatic assay, and fragments were prepared for electron microscopy. No histamine was detectable in any artery studied. The 5-HT content of arteries from control animals and those perfused with vehicle (in vivo) or incubated in the physiological solution (in vitro) was 250-300 pmol/mg protein. Both compound 48/80 and carbachol reduced this amount by approximately 50% and induced a marked degranulation of mast cells. Both secretion and degranulation were dramatically blocked in vitro by atropine. No difference in the 5-HT content was observed between intact and sympathectomized arteries under any condition. We conclude that a large proportion of rabbit cerebrovascular 5-HT is stored in mast cells and that cholinergic nerve activation could theoretically release this pool by acting on mast cell muscarinic receptors.
Ontogeny of cholinergic and adrenergic mechanisms in the frog (Rana temporaria) heart
Authors: Protas L. L. , Leontieva G. R.
Published: December 2017

Histochemical techniques, field stimulation, and application of autonomic drugs were used to study neurotransmission in the heart during ontogenesis of Rana temporaria. Cholinesterase (ChE)-containing fibers, fluorescent chromaffinlike cells, and fluorescent fibers were found first in the heart at tadpole stages 40, 40, and 50, respectively. Inhibitory cholinergic and stimulatory adrenergic responses to field stimulation first appeared at stages 39-40 and 42, respectively. Inhibitory responses to acetylcholine (ACh) and stimulatory responses to epinephrine (Epi) were observed as early as stages 31 and 32. The concentrations producing half-maximal response values for both neurotransmitters increased during development. Indirect evidence was obtained that the subsensitivity of tadpole hearts to ACh was due to increased hydrolysis of ACh by tissue ChE and that the subsensitivity of adult frog heart to Epi could be connected with a maturation of the neuronal uptake mechanism. The pA2 values for atropine and propranolol were 10 times greater in tadpoles than in adults. The main conclusion is that the cholino- and adrenoreactive systems appear in the frog heart cells before they become innervated and the sensitivity of these systems to neurotransmitters does not increase with innervation.
Cardiovascular and renal effects of gamma-MSH in spontaneously hypertensive and normotensive Wistar Kyoto rats
Authors: Sun X. Y. , Feng Q. P. , Gong Q. L. , Edvinsson L. , Hedner T.
Published: December 2017

The objective of this study was to compare the cardiovascular and renal effects of the two gamma-melanocyte-stimulating hormone (MSH) peptide sequences in the pro-opiomelanocortin prohormone structure in conscious, anesthetized, and pithed spontaneous hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) controls. In the conscious but not in the pithed rats, intravenous injection of gamma 2- and gamma 1-MSH induced a rapid and dose-dependent increase in mean arterial pressure (MAP), and gamma 2-MSH was more potent than gamma 1-MSH. The pressor response was more pronounced and more sustained in the SHR compared with the WKY. There were dose-dependent and significant increases in heart rate (HR) after gamma 2- and gamma 1-MSH in the SHR. At intravenous infusions of low doses of gamma 2-MSH, which did not significantly influence MAP or HR, urinary sodium excretion was significantly increased in both SHR and WKY. In conscious, but not in anesthetized rats, intracerebroventricular administration of the gamma 2-MSH peptide induced sustained increases in MAP in both SHR and WKY. After intrathecal administration, there were transient pressor effects of gamma 2-MSH. We conclude that the pro-opiomelanocortin-derived gamma 2- and gamma 1-MSH peptide sequences possess potent rapid pressor actions. The pressor effects, which require an intact sympathetic nervous system, are more pronounced in the SHR strain. Moreover, gamma 2-MSH induces natriuresis when administered in nonpressor doses in WKY and SHR.
Increased loop chloride uptake precedes hypertension in Dahl salt-sensitive rats
Authors: Kirchner K. A.
Published: December 2017

When studied at equivalent renal perfusion pressures, loop segment chloride reabsorption is greater in hypertensive Dahl salt-sensitive (S) than Dahl salt-resistant (R) rats. To determine whether this difference in loop reabsorption is present before the onset of hypertension, volume expanded and euvolemic Dahl rats maintained on low NaCl diets were examined using micropuncture and in vivo microperfusion techniques. Neuroendocrine differences between groups were eliminated by renal denervation and fixing plasma aldosterone, norepinephrine, and vasopressin levels. After volume expansion, urinary NaCl excretion was less in S than R rats. Early distal tubule fluid-to-plasma chloride and inulin (TF/PCl/IN) ratio and chloride delivery were also less while loop chloride reabsorption was greater in S rats. Proximal delivery was not different between groups. In euvolemia, urinary NaCl excretion and loop chloride reabsorption were not different between S and R rats. However, when loop chloride delivery was increased by microperfusion techniques, lower distal TF/PCl/IN ratios and greater loop chloride reabsorption were clearly demonstrated in euvolemic S rats. Thus loop chloride reabsorption is greater in S than R rats before the development of hypertension. This difference depends on increasing delivery rates for its manifestation.
Recovery metabolism of trout white muscle: role of mitochondria
Authors: Moyes C. D. , Schulte P. M. , Hochachka P. W.
Published: December 2017

Recovery from burst exercise in fish is very slow. Lactate conversion to glycogen occurs primarily within white muscle and must be fueled by mitochondrially produced ATP. In a parallel study we characterized the changes in tissue metabolites associated with burst exercise and recovery in rainbow trout (Oncorhynchus mykiss) white muscle. The present study examines whether the mitochondrial capacity to produce ATP may limit the rate of recovery of trout white muscle. The cost (ATP.min-1.g-1) of glycogen resynthesis (0.05 mumol lactate converted.min-1.g tissue-1) was compared with the mitochondrial capacity to produce ATP. The cost of recovery can be met by only 3.5% of the maximal mitochondrial capacity. In fact, during recovery trout white muscle mitochondria operate at a small fraction of their in vitro maximum. This capacity is suppressed in vivo by highly inhibitory ATP/ADP and limiting phosphate. The primary signal for increased ATP synthesis associated with recovery is not a change in ATP/ADP but probably phosphate, elevated because of phosphocreatine hydrolysis and adenylate catabolism in the purine nucleotide cycle. At low ADP availability and suboptimal phosphate (less than 5 mM), acidosis enhances respiration. At high respiratory rates mitochondrial pyruvate oxidation is sensitive to pyruvate concentration over the physiological range (apparent Michaelis constant = 35-40 microM). This sensitivity is lost at the low rates that approximate in vivo respiration. Changes in lactate do not affect the kinetics of pyruvate oxidation. Fatty acid oxidation may spare pyruvate and lactate for use in glyconeogenesis, primarily through allosteric inhibition of pyruvate dehydrogenase rather than covalent modification.
Cerebral metabolic responses and vasopressin and oxytocin secretions during progressive water deprivation in rats
Authors: Kadekaro M. , Summy-Long J. Y. , Freeman S. , Harris J. S. , Terrell M. L. , Eisenberg H. M.
Published: December 2017

Progressive water deprivation increased plasma osmolality, plasma Na+ concentration, and hematocrit in proportion to the severity of dehydration. With increases of 2% in plasma osmolality (24 h dehydration), glucose utilization increased in the supraoptic nuclei and tended to increase in the neural lobe. With further dehydration, glucose utilization also increased in the paraventricular nuclei. These increases were paralleled by depletion of vasopressin and oxytocin contents in the neural lobe and by the enhanced secretion of both hormones into plasma, with a predominant increase of vasopressin. These changes were proportional to the degree of dehydration. With progression of dehydration, decreases in intracellular and extracellular volumes accentuate. Reductions in extracellular volume result in increased angiotensin II (ANG II) formation. Accordingly, glucose utilization in the subfornical organ (SFO), a primary site of ANG II action, increased after 48 and 72 h of dehydration. The median preoptic nucleus, which receives direct inputs from the SFO, also increased glucose utilization at these times. Glucose utilization also increased in the organum vasculosum laminae terminalis, probably in response to the converging inputs from osmoreceptors, volume receptors, and ANG II receptors. Decreases in glucose utilization were observed in the caudal and rostral ventrolateral medulla, perhaps as compensatory responses to decreased extracellular volume to prevent fall in arterial blood pressure.
Switches in cardiac muscle gene expression as a result of pressure and volume overload
Authors: Schwartz K. , Boheler K. R. , de la Bastie D. , Lompre A. M. , Mercadier J. J.
Published: December 2017

In the mammalian heart, the expression of genes encoding proteins responsible for contraction, relaxation, and endocrine function changes in hypertrophy resulting from hemodynamic overload. Different mechanisms are involved in this mechanogenic transduction, including 1) differential expression of myosin and actin multigene families, which may account for the decreased velocity of contractile element shortening in hypertrophied heart, 2) nonactivation of the sarcoplasmic reticulum Ca(2+)-ATPase gene, which may explain the increased duration of isometric relaxation, and finally 3) activation in the ventricle of the atrial natriuretic factor gene that is responsible in part for the high plasma levels of this peptide. It is increasingly apparent that these changes are independently regulated, but little is known about the mechanisms underlying this regulation. Preliminary results indicate that it is now possible to analyze the early time course or transcription for each gene after the imposition of hemodynamic overload. This should significantly enhance our understanding of the regulatory mechanisms involved in the phenoconversions of the hemodynamically overloaded heart.
Scaling of bodily proportions in adult terrestrial mammals
Authors: Prothero J.
Published: December 2017

To model body shape, a data base was constructed for body, forelimb, and hindlimb length, surface area, and girth, each as a function of body weight, in a diversity of mammals. These data were submitted to linear least-squares regression analysis. In addition, data on the partitioning of weight and surface area among the body segments (head-trunk, forelimbs, and hindlimbs) were collected. These data imply a relatively constant partitioning of body weight and surface area among the body segments. The regression parameters and the body segment data were used to build and test a model of bodily proportions. The model consists of three classes of cylinders, each specified by a length and a diameter, representing the three classes of body segments. The parameters of the model were constrained to enforce geometric similarity (constant shape). The model was found to agree reasonably well with an independent subset of the data. It is concluded that adult land mammals do exhibit geometric similarity over a substantial weight range.