bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating behavior and cardiovascular responses: the code
Authors: Astley C. A. , Smith O. A. , Ray R. D. , Golanov E. V. , Chesney M. A. , Chalyan V. G. , Taylor D. J. , Bowden D. M.
Published: December 2017

The next revolution in biology is predicted to be in the integrative domain, and the need to involve physiologists in this kind of research has been recognized. This paper represents an approach to providing some of the tools required for dealing with integrative physiology at the behavioral level. Video tape recordings are made of the activities of a group of five baboons (Papio hamadryas) while simultaneous recordings of arterial blood pressure, heart rate, renal blood flow, and mesenteric or iliac blood flow are telemetered from two of the members of the group. The telemetered cardiovascular information is recorded on the two audio channels of the videotape. Subsequently the videotape is viewed, and a two-dimensional code is used to record the behavior of the two animals with the telemetry equipment. The first dimension of the code categorizes the behavior changes precisely regarding those aspects of behavior that are related to cardiovascular dynamics and does so with an accuracy of 16 ms. The second dimension codes relevant environmental changes. The paper describes the code and presents illustrations of how the code reflects the cardiovascular dynamics associated with the behavioral changes.
Characterization and development of angiotensin II receptor subtypes (AT1 and AT2) in rat brain
Authors: Tsutsumi K. , Saavedra J. M.
Published: December 2017

Angiotensin II receptor subtypes (AT1 and AT2) were characterized in rat brain by displacement with the specific angiotensin antagonists Du Pont 753 and CGP 42112A, respectively, and quantitative autoradiography. Young (2-wk-old) rats expressed AT1 receptors in selected limbic system areas, structures involved in cardiovascular and fluid regulation, parts of the hippocampal formation, and the choroid plexus. In young rats, AT2 receptors were concentrated in areas involved in control and learning of motor activity, sensory areas, and selected limbic system structures. The cingulate cortex, the molecular layer of the cerebellar cortex, and the superior colliculus contained both AT1 and AT2 receptors. The number of AT1 receptors in most areas of adult (8-wk-old) rats was similar to or even higher than that present in young rats. Conversely, AT2 receptors were always much lower in number in adult animals, and in some areas they were undetectable in adults. Their differential localization and development suggest different functions for the specific angiotensin II receptor subtypes.
Acid-base regulation in exercising squid (Illex illecebrosus, Loligo pealei)
Authors: Portner H. O. , Webber D. M. , Boutilier R. G. , O'Dor R. K.
Published: December 2017

Squid (Illex illecebrosus, Loligo pealei) were cannulated in the vena cava and swum in a Beamish-type respirometer. Gas tensions and acid-base variables as well as octopine levels were estimated in samples of the mantle and of venous blood collected from quiescent, exercised, and recovered animals. When exhausted, both species exhibited a decrease in vena cava oxygen tensions and a slight alkalosis. With high swimming speeds prior to exhaustion in Illex a slight acidosis developed in the blood, which was linked to a severe intracellular acidosis. Generally, the drop in intracellular pH was linearly correlated with octopine accumulation in this species. Metabolic proton (and end-product) release from the mantle, however, was minimal, thus protecting arterial oxygen binding. High PCO2 values in the mantle of both species lead to the conclusion that the vena cava values analyzed in this and all literature studies on unrestrained cephalopods may not reflect the scope of respiratory acid-base changes in venous blood. Although metabolic changes in blood acid-base status are negligible, the respiratory acidification of venous mantle blood may allow for a classical function of Bohr and Haldane effects in these animals.
Arterial baroreflex control of cardiac and renal sympathetic nerve activities is uniform in frequency domain
Authors: Harada S. , Ando S. , Imaizumi T. , Hirooka Y. , Sunagawa K. , Takeshita A.
Published: December 2017

To investigate wideband dynamic properties of arterial baroreflex control of cardiac and renal sympathetic nerve activities, we assessed the transfer function using a "white-noise technique." In pentobarbital sodium-anesthetized cats, we simultaneously recorded, as the output, cardiac sympathetic nerve activity (CSNA) and renal sympathetic nerve activity (RSNA), while aortic pressure (AP) was randomly perturbed to impose input pressure changes with broad frequencies. We calculated the transfer function from AP to CSNA or to RSNA over the frequency range of 0.01-5 Hz through the spectral analysis of the input and output. We found that the gain, phase shift, and coherence of those transfer functions were statistically indistinguishable. The gain was rather flat below 0.05 Hz, steadily increased above 0.05 Hz, and plateaued above 0.3 Hz. The phase shift was out of phase up to 0.05 Hz and led by approximately 4 degrees above 0.05 Hz. The coherence was high (above 0.7) below 0.3 Hz and became lower above 0.3 Hz. These results suggest that arterial baroreflex control is uniform and similar between the two activities in the frequency range of 0.01-0.7 Hz.
Activation of renal mechanoreceptors increases vasopressin release in rabbits
Authors: Yamamoto A. , Keil L. C. , Reid I. A.
Published: December 2017

Electrical stimulation of afferent renal nerves increases plasma vasopressin (AVP) concentration, but the role of these nerves in the control of AVP release is not known. The aim of the present study was to investigate the effect of activation of renal mechanoreceptors and chemoreceptors on plasma AVP concentration in anesthetized rabbits. Intrapelvic pressure was increased to activate renal mechanoreceptors, and the renal pelvis was perfused with 1.0 M NaCl, 0.1 M KCl, and 1.0 M mannitol solutions to activate R2 chemoreceptors. With increased pelvic pressure, plasma AVP concentration increased from 12.4 +/- 3.8 to 36.2 +/- 16.1 pg/ml at 5 min and to 37.4 +/- 16.1 pg/ml at 10 min (P less than 0.01). Plasma renin activity increased from 15.7 +/- 4.0 to 22.1 +/- 3.3 ng.ml-1.2 h-1 (P less than 0.05), but blood pressure and heart rate did not change significantly. Similar increases in plasma AVP concentration occurred during perfusion of the renal pelvis with 1.0 M NaCl (17.6 +/- 8.1 to 53.7 +/- 24.0 pg/ml), 0.1 M KCl (9.2 +/- 2.1 to 39.7 +/- 17.3 pg/ml), and 1.0 M mannitol (27.5 +/- 10.9 to 77.5 +/- 30.8 pg/ml) solutions. However, because pelvic pressure increased by 40-50 mmHg during the perfusions, the experiments were repeated with use of a different perfusion method in which pelvic pressure increased by less than 5 mmHg. Under these conditions, plasma AVP concentration did not change significantly during perfusion with any of the solutions. To determine whether the mechanoreceptor-induced increase in AVP release is mediated by the renal nerves, pelvic pressure was increased in another group of rabbits after renal denervation.(ABSTRACT TRUNCATED AT 250 WORDS)
Normal food intake and growth in hyperprolactinemic rats
Authors: Adler R. A. , Krieg R. J.
Published: December 2017

Normal lactation, a state of chronic hyperprolactinemia, is often accompanied by increased food intake. Two recent reports suggested that, in rats, prolactin (PRL) administration or chronic endogenous PRL excess led to increased food intake and growth. Similar methods of achieving augmented circulating levels of PRL in rats have been employed in our laboratory. Rats with extra anterior pituitary (AP) grafts under the kidney capsule have chronically elevated circulating PRL levels. However, in several experiments, weight gain, food intake, and fecal weight were the same in AP-grafted rats and in control muscle-grafted rats. In addition, the AP-grafted rat model was modified to demonstrate that PRL-induced increases in adrenal glucocorticoids and decreases in estrogens did not provoke alterations in eating behavior. Injection of homologous PRL for 8 days did not increase weight gain in normal or hypophysectomized rats. These data suggest that neither the chronic PRL excess caused by AP grafts nor the acute PRL excess caused by rat PRL injections increases food intake or weight gain.
Defining origin of positive slope in hypercapnic ventilatory response curve
Authors: Lorinc Z. , Derr J. , Snider M. , Lydic R.
Published: December 2017

The sensitivity to CO2 as a respiratory stimulant has traditionally been studied by exposing organisms to progressively increasing levels of inspired CO2 while measuring the corresponding increase in minute ventilation (V). Plots of V as a function of end-tidal CO2 concentration reveal a complex function with a "dogleg" shape. Only the positive slope of the V function is taken as an index of chemosensitivity, but the starting points for such analyses are often chosen arbitrarily. This paper examined the hypotheses that the range of CO2 concentrations over which V slopes are compared may be mathematically defined and that arbitrary choices of this analytic range may influence conclusions about the hypercapnic ventilatory response (HCVR). Three mathematical models attempted to define the origin of the positive slope for the HCVR curve using empirically derived data. The results revealed good agreement that the origin of the positive HCVR slope may be reliably defined by a point that joins the horizontal and positive slope of the HCVR curve. In addition to identifying the "joint-point" statistic, the results suggest that arbitrarily defining the range of CO2 values over which V is analyzed can be replaced by quantitative approaches for identifying the origin of the ventilatory response to hypercapnia.
Albumin enhances negative feedback effect of cortisol on ACTH release from sheep pituitary cells
Authors: Kemppainen R. J. , Zerbe C. A. , Sartin J. L.
Published: December 2017

Albumin binds circulating glucocorticoids such as cortisol and consequently may modify the biological activity of these steroids by altering access to target cells. Because albumin is likely present in pituitary interstitial fluid, this study was designed to compare the negative feedback effect of cortisol on pituitary adrenocorticotropic hormone (ACTH) secretion from isolated sheep pituitary cells perifused with media containing 0.25% or 2% bovine serum albumin (BSA). Pituitary cells released less (P less than 0.05) immunoreactive ACTH in response to a 10-min treatment with 10 nM ovine corticotropin-releasing hormone (oCRH) after 45 min pretreatment with 0.5 microM cortisol when media contained 2% BSA vs. 0.25% BSA. A similar enhancement in negative feedback potency was observed when cells were treated with cortisol followed by 1 nM oCRH for 60 min, with an additional 10 min co-addition of arginine vasopressin. This potentiation was not observed when a noncortisol binding protein, ovalbumin, was substituted for BSA. However, the potentiating effect of albumin was present in perifused rat pituitary cells, indicating that the effect was not species specific. We conclude that albumin enhances the negative feedback potency of cortisol in anterior pituitary corticotrophs and that the process may operate under physiological conditions to enhance cell specific delivery of this steroid to appropriate targets.
Blood pressure maintenance in hypertensive sympathectomized rats. II. Renin-angiotensin system and vasopressin
Authors: Lo M. , Julien C. , Barres C. , Medeiros I. , Allevard A. M. , Vincent M. , Sassard J.
Published: December 2017

This study examined the contribution of the main pressor systems to the residual hypertension exhibited by genetically hypertensive (LH) rats of the Lyon strain after early chronic sympathectomy with guanethidine. Blood pressure (BP) was recorded in conscious LH and normotensive control (LN) rats, either intact or sympathectomized, during sequential blockade of the renin-angiotensin system, vasopressin receptors, the autonomic nervous system, and finally after maximal vasodilation with hydralazine. In sympathectomized rats 1) renin-angiotensin system blockade equally reduced BP in both strains, whether it was realized before (-20%) or after (-30%) vasopressin antagonism; 2) isolated vasopressin antagonism decreased BP in LH (-8%) but not in LN rats; 3) autonomic blockade and hydralazine induced additional decreases in BP that were similar in both strains; and 4) intermediate and final levels of BP remained always higher in LH than in LN rats. It is concluded that, after sympathectomy, BP is maintained primarily by the renin-angiotensin system. In sympathectomized LH rats, the maintenance of hypertension does not depend on hyperactivity of the main pressor systems but rather on an increase in the intrinsic vascular resistance that develops in the absence of the sympathetic innervation of the vessels.
BAY K 8644 and nifedipine alter halothane but not caffeine contractures of malignant hyperthermic muscle fibers
Authors: Williams J. H. , Holland M. , Lee J. C. , Ward C. W. , McGrath C. J.
Published: December 2017

The purpose of these experiments was to determine if the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine alter the mechanical responses of malignant hyperthermia-susceptible (MHS) skeletal muscle to halothane and caffeine. Muscle fiber bundles were dissected from MHS porcine skeletal muscle and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), low-Ca2+ media [Ca2+ replaced by 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], or diltiazem (30 microM) administered alone and with halothane (3%) or caffeine (0.5-0.8 mM). When administered alone, both halothane and BAY K 8644 evoked a significant change in resting tension (i.e., contracture) of 193.7 +/- 61.0 and 51.9 +/- 21.5 mN/cm2, respectively. When administered in combination, BAY K 8644 had no effect on the magnitude of the halothane contracture (195.2 +/- 58.6 mN/cm2) but reduced its onset time from 306.7 +/- 36.3 to 105.9 +/- 8.9 s. Nifedipine, low Ca2+, and diltiazem significantly reduced the halothane contracture (103.1 +/- 30.3, 123.1 +/- 20.6, and 112.6 +/- 16.2 mN/cm2, respectively) but had no effect on its onset time. In addition, low Ca2+ reduced the magnitude of the BAY K 8644 contracture (8.2 +/- 2.1 mN/cm2). BAY K 8644 also increased contractures induced by low caffeine concentrations (0.5-2.0 mM) but did not alter contractures induced by 4.0 and 8.0 mM caffeine, whereas nifedipine, low Ca2+, and diltiazem had no effect on these contractures. These results suggest that extracellular Ca2+ influx may have some influence on halothane but not on caffeine contractures of MHS skeletal muscle.
Pressure diuresis and autonomic function in conscious dogs
Authors: Brand P. H. , Coyne K. B. , Kostrzewski K. A. , Shier D. , Metting P. J. , Britton S. L.
Published: December 2017

Pressure diuresis is thought to be a major long-term regulator of arterial blood pressure (AP). Previously, pressure diuresis has been characterized using pharmacological or surgical blockade of other mechanisms known to affect renal function. This study evaluated pressure diuresis in conscious dogs with minimal experimental interference. Dogs were chronically instrumented under pentobarbital anesthesia with aortic and urinary bladder catheters. AP was increased by 10% in resting dogs by exposure to increased light and sound intensity (arousal) for 90 min. During arousal, urine flow (UV) and Na+ excretion (UNa+ V) correlated with AP (UV vs. AP, r = 0.12, P less than 0.05; UNa+ V vs. AP, r = 0.19, P less than 0.005; 17 trials in 7 dogs). Arousal did not affect the plasma concentration of atrial natriuretic factor, suggesting that this hormone did not contribute to the correlations between UV or UNa+ V and AP. Because arousal may induce an autonomically mediated antidiuresis, studies were repeated during autonomic ganglionic blockade with hexamethonium. During autonomic blockade, the correlations between UV or UNa+ V and AP were increased (UV vs. AP, r = 0.72; UNa+ V vs. AP, r = 0.72, P less than 0.001; 6 trials in 4 dogs). We conclude that the effect of pressure diuresis on UV and UNa+ V can be detected in the intact animal, during normal operation of all the mechanisms that control renal function. Furthermore, when autonomic reflexes are blocked, the pressure-diuresis mechanism is a major determinant of UV and UNa+ V.
Dietary obesity and weight cycling in rats: a model of stress-induced hypertension?
Authors: Contreras R. J. , King S. , Rives L. , Williams A. , Wattleton T.
Published: December 2017

The present study was designed to reproduce the mild hypertension seen in dietary obese weight-cycled rats [P. Ernsberger and D. O. Nelson. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R47-R55, 1988] and determine whether this mild hypertension was associated with changes in sodium excretion and pressor responsiveness to angiotensin II (ANG II). Male Sprague-Dawley rats were fed pelleted chow (Pellet group) or chow plus sweetened condensed milk (Milk group) or were exposed to four cycles of a 4-day fast alternated with 2 wk of refeeding of pelleted chow and sweetened condensed milk (Cycled group). Blood pressure and heart rate were measured by tail cuff at the onset and last day of each fast and after 3 days of refeeding. During fasting, urine sodium excretion was measured. Mean arterial pressure and heart rate responses to intravenous administration of ANG II (40, 80, and 120 ng/kg), metoprolol (1 mg/kg), and methyl scopolamine (2 mg/kg) were obtained from the femoral artery in awake unrestrained rats. Weight cycling did not lead to mild hypertension or increased bradycardic response to sympathetic blockade with metoprolol. ANG II-elicited pressor responses were similar for Pellet, Milk, and Cycled groups. Sodium excretion did not change with fasting. Mild hypertension developed when obese weight-cycled rats were housed together in groups and not when housed individually. Our preliminary data are consistent with the notion that stress associated with group housing may be a factor in the mild hypertension of obese weight-cycled rats.
Adrenal sympathetic nerve activity in response to hypothalamic injections of 2-deoxy-D-glucose
Authors: Yoshimatsu H. , Egawa M. , Bray G. A.
Published: December 2017

Adrenal sympathetic nerve activity after microinfusion of 2-deoxy-D-glucose (2-DG) into various hypothalamic nuclei was investigated in anesthetized rats. Infusion of 2-DG into the ventrolateral portion of the lateral hypothalamic area (LHA) induced a large and long-lasting increase (greater than 60 min) in adrenal nerve activity. In contrast, infusion into the dorsal or medial portion of the LHA tended to produce a small decrease with a return to baseline within approximately 60 min after the end of the infusion. The direct administration of 2-DG into either the paraventricular nucleus or the dorsomedial hypothalamic nucleus produced a strong inhibition of adrenal nerve activity. Infusions into the ventromedial hypothalamic nucleus induced either a decrease of adrenal nerve activity or were without effect. These findings provide evidence that induction of glucoprivation in the hypothalamus with 2-DG can excite or inhibit adrenal nerve activity, depending on the hypothalamic region. These data also indicate that the ventrolateral portion of the LHA plays an important role in the regulation of adrenal catecholamine secretion in response to glucoprivic conditions in the central nervous system.
Differentiation of two cardiovascular regions within caudal ventrolateral medulla
Authors: Cravo S. L. , Morrison S. F. , Reis D. J.
Published: December 2017

The caudal ventrolateral medulla (CVLM) plays a significant role in the regulation of sympathetic nerve activity (SNA) and arterial pressure; however, the use of lesions to examine its role in mediating baroreceptor reflex control of SNA has yielded discrepant results. We hypothesize that this may have arisen from anatomic segregation of neurons within the CVLM that subserve different functions in sympathetic control. Thus we used microinjections of the excitotoxic agent kainic acid (200 pmol in 20 nl) to determine the effects of inactivation of neuronal cell bodies in a rostral and a caudal subregion of the CVLM on SNA, arterial pressure, and baroreceptor reflex function in urethan-anesthetized rats. Interruption of neuronal activity in the rostral CVLM (sites from 0.6 mm caudal to 0.5 mm rostral to the rostral border of the lateral reticular nucleus) elevated SNA (post-kainic acid 214% of control) and arterial pressure (+34 mmHg) and eliminated the inhibition of splanchnic SNA evoked by either aortic nerve stimulation or the pressor response to intravenous norepinephrine. In addition, the cardiac-related component of spontaneous SNA was abolished as judged from post-R wave averages and from power spectral analysis. In contrast, although a similar disruption of neuronal activity in the caudal CVLM (sites 0.0-0.6 mm rostral to the caudal border of the lateral reticular nucleus) produced a comparable increase in spontaneous SNA (post-kainic acid 196% of control) and arterial pressure (+20 mmHg), it was without effect on the ability of the baroreceptor reflex to inhibit SNA, and it enhanced the synchronization of the spontaneous bursts in SNA to the cardiac cycle. Our results suggest an organization of the CVLM in which neurons in its rostral portion are required for an effective baroreceptor reflex, whereas those in the caudal CVLM serve to limit SNA and blood pressure independent of the baroreceptor reflex.
ACTH response in rats during biphasic fever induced by interleukin-1
Authors: Watanabe T. , Morimoto A. , Murakami N.
Published: December 2017

Injection of a low concentration (0.3 micrograms/kg iv) of interleukin-1 beta (IL-1 beta) produced monophasic fever, but high concentrations (15 micrograms/kg iv) produced biphasic fever in rats. Treatment with IL-1 beta caused dose-dependent rises in the plasma concentration of adrenocorticotropic hormone (ACTH) 30 min after injection. Moreover, significant increases in plasma levels of ACTH were observed 90 and 180 min after injection of the high dose of IL-1 beta. ACTH response induced by IL-1 beta (15 micrograms/kg iv) was suppressed by pretreatment with injection of indomethacin (Indo), a potent inhibitor of prostaglandin (PG) synthesis, in a dose-dependent manner (1 and 10 mg/kg iv). Also, biphasic fever induced by the high dose of IL-1 beta was completely abolished by pretreatment with the intravenous injection of Indo. Intracerebroventricular (icv) injection of Indo (50 micrograms) did not affect febrile and ACTH responses induced by intravenous IL-1 beta, whereas those responses induced by IL-1 beta (2 ng icv) were significantly suppressed by injection of Indo (50 micrograms icv). Although it is possible that intracerebroventricular Indo does not reach the site of intravenous IL-1 beta action within the brain, these results suggest that in rats febrile and ACTH responses induced by intravenous IL-1 beta are caused by IL-1 beta-acting structures outside the blood-brain barrier. It is likely that these structures subsequently synthesize and release PGE2, which in turn induces ACTH and febrile responses in rats.
Taurine secretion in cultured winter flounder renal epithelium
Authors: Perlman D. F. , Renfro J. L. , Goldstein L.
Published: December 2017

The mechanism for the secretion of taurine by the marine fish kidney was examined in flounder renal primary cultures and teased tubules. The question addressed was whether the secretion of taurine, but not beta-alanine, a related beta-amino acid, is due to differences in their basolateral uptake, intracellular concentration, or luminal efflux mechanism. Aminooxyacetate (AOA) (10 mM), an inhibitor of beta-alanine oxidation, allowed the basolateral beta-alanine accumulation (measured in teased tubules) and the beta-alanine intracellular concentration (measured in primary cultures) to be similar to that for taurine. However the addition of AOA did not promote the net secretion of beta-alanine (measured as unidirectional fluxes in the cultured epithelium mounted in an Ussing chamber). The organic anions bromcresol green (BCG) (0.1 mM) and probenecid (1 mM) inhibited the net secretion of taurine by affecting the luminal efflux step. This suggests that a BCG- and probenecid-sensitive carrier in the luminal membrane facilitates the cell-to-lumen efflux of taurine and thus achieves net secretion.
Renal nerves and postprandial renal excretion in the conscious monkey
Authors: Peterson T. V. , Benjamin B. A. , Hurst N. L. , Euler C. G.
Published: December 2017

Experiments were performed in conscious macaque monkeys to determine if the renal nerves are important in mediating postprandial increases in renal fluid-electrolyte excretion in this species. Monkeys were given a high-sodium meal via a nasogastric tube. Consecutive 10-min urine samples were taken during the 30-min time of meal administration and then 180 min postprandially. The experiment was performed both before and 10-14 days after each animal underwent renal denervation. Diuresis and natriuresis occurred under both renal-innervated and -denervated conditions. However, the amounts of urine and sodium excreted were less after renal denervation. For the total 210 min of measurements obtained after the meal was started, cumulative urine output was 95.0 +/- 26.4 ml and sodium excretion 7.18 +/- 1.74 meq in innervated kidneys vs. 56.7 +/- 7.0 ml (a 40% decrease; P less than 0.005) and 4.84 +/- 0.99 meq (a 33% decrease; P less than 0.01) after denervation. These results demonstrate that the renal nerves are important in the nonhuman primate for eliciting the postprandial changes in urinary excretion secondary to intake of a high-sodium meal.
Changes in soluble carbonic anhydrase activity in response to maturation and NH4Cl loading in the rabbit
Authors: Brion L. P. , Zavilowitz B. J. , Rosen O. , Schwartz G. J.
Published: December 2017

Maturation and systemic acidosis are two factors that stimulate urinary acidification. Proton secretion, CO2 handling, and some metabolic processes are facilitated by cytosolic carbonic anhydrase (CA). The activity of this enzyme in kidney, red blood cells (RBCs), and liver could be regulated in response to acid-base perturbations or maturation. Therefore, we investigated the effects of maturation and NH4Cl acid loading on soluble CA hydratase activity in RBCs, kidneys, and livers of female New Zealand White rabbits during three stages of maturation (neonatal, 4 wk, and adult). Total RBC CA activity doubled with maturation but did not increase after NH4Cl loading. There was substantial interindividual variation in the amount of CA I related activity. In the kidney we found intrinsic cortical CA II activity to be more than twice that in the outer medulla, which was more than twice that in the inner medulla. CA activity doubled with maturation in the cortex and increased by 70% in the outer medulla. Twenty hours after an NH4Cl load there was a 50% increase in renal cortical CA activity in 4-wk-old rabbits, but a comparable increase in cortical CA activity was only seen after 3-5 days of NH4Cl loading in adult animals. In the liver a third of cytosolic CA activity was acetazolamide resistant, presumably CA III, which doubled with maturation. Chronic NH4Cl loading in adult animals induced an almost 60% increase in hepatic acetazolamide-sensitive CA activity (mostly CA II). These data show that in the rabbit there is a renal corticomedullary gradient in soluble CA activity (mostly CA II), with significant activity in the inner medulla. Maturation induced total CA activity in the inner medulla. Maturation induced total CA activity in RBCs, CA II activity in kidney cortex and outer medulla, and CA III in the liver. Finally, CA II activity in kidney cortex and liver appeared to be regulated in response to some conditions of NH4Cl loading.
Comparative insights into the mechanisms of renal organic anion and cation secretion
Authors: Pritchard J. B. , Miller D. S.
Published: December 2017

Comparative models have played a major role in defining the mechanisms that enable vertebrate proximal tubules to transport organic anions and cations from the peritubular interstitium to the urine. The unique advantages of these models and their contributions to our understanding of organic anion and cation transport mechanisms are summarized here. Recent studies of the organic anion transport system suggest that transport is coupled to metabolic energy via indirect coupling to the sodium gradient. Organic anions enter the cell across the basolateral membrane in exchange for alpha-ketoglutarate (alpha-KG), and the alpha-KG is returned to the interior via Na-alpha-KG cotransport. Indirect coupling to Na has been demonstrated in both isolated membranes and intact renal epithelial cells of species ranging from marine crustaceans to mammals. This mechanism was shown to drive not only cellular accumulation but also secretory transepithelial fluxes of organic anions. Luminal exit of secreted organic anions appears to be carrier mediated but is, at present, poorly understood, with mediated potential-driven efflux and anion exchange-driven efflux implicated in some species. As for organic anions, the renal clearance of some organic cations approaches the renal plasma flow. Although there is considerable variation in the handling of specific substrates between species, the basic properties of organic cation transport include carrier-mediated potential-driven uptake at the basolateral membrane, intracellular sequestration that reduces the free concentration of the cation, and luminal exit by organic cation-proton exchange. Reabsorptive transport is also observed for some organic cations, but its mechanisms and driving forces are not well understood.
Role of adrenal catecholamines during forced submergence in ducks
Authors: Lacombe A. M. , Jones D. R.
Published: December 2017

Maximum underwater tolerance (UTmax) of chronically adrenalectomized ducks (ADX, 5.3 +/- 0.3 min) and chronically adrenal-denervated ducks (DNX, 7.2 +/- 0.2 min) was significantly lower than sham-operated controls (SH-ADX, 10 +/- 0.8 min; SH-DNX, 12.2 +/- 0.5 min). After 4 min forced submergence, heart rates of ADX (62 +/- 16 beats/min) and DNX (31 +/- 2 beats/min) ducks were significantly higher than in their respective sham-operated controls (23 +/- 3 and 17 +/- 2 beats/min), although their blood pressure was significantly lower. Arterial partial pressure of O2, arterial O2 content, arterial pH, and lactate levels in DNX ducks (42 +/- 2 mmHg, 4.5 +/- 0.8 ml O2/100 ml blood, 7.233 +/- 0.016, 3.1 +/- 0.3 mM, respectively) were significantly lower than in SH-DNX ducks after 5 min forced submergence (53 +/- 1 mmHg, 6.8 +/- 0.4 ml O2/100 ml blood, 7.301 +/- 0.007, 4.8 +/- 0.4 mM, respectively). Venous infusion of catecholamines in ADX and DNX ducks during forced submergence significantly increased UTmax. It is suggested that adrenal catecholamines increase tolerance to underwater submersion by enhancing peripheral vasoconstriction, thus preserving the O2 stores for the heart and brain. Other adrenal products could also be involved.
Mechanisms involved in the rapid dissipation of plasma epinephrine response to bacterial endotoxin in conscious rats
Authors: Qi M. , Zhou Z. Z. , Wurster R. D. , Jones S. B.
Published: December 2017

Conscious rats treated with bolus endotoxin (ET; 4.0 mg/kg) increased plasma epinephrine (Epi) 48-fold (from 134 +/- 5 to 6,545 +/- 1,607 pg/ml) at 30 min, but by 6 h this elevation was less than 9-fold above control (1,174 +/- 166 pg/ml). In contrast, plasma norepinephrine (NE) elevation (6.5-fold above control) was maintained during the protocol. The present study was designed to test the hypothesis that the decreased Epi response following ET was due to 1) depletion of adrenal Epi content such that adrenomedullary stimulation would not release Epi, 2) decreased Epi release with direct stimulation, i.e., desensitization of release, or 3) decreased afferent signals generated by ET itself. In these experiments an initial low ET dose (0.5 mg/kg) was followed 3 h later by a second dose of either the same (0.5 mg/kg) or greater (4.0 mg/kg) magnitude. Plasma Epi was elevated following the initial (low) dose but not following the same second (0.5 mg/kg) dose, whereas the second higher dose (4.0 mg/kg) resulted in elevated plasma Epi. This response to high dose was 60% less than that observed with 4.0 mg/kg as an initial dose. Just before the second ET bolus, there was no depletion of adrenal Epi content (P greater than 0.05 saline vs. ET treated), and direct nerve stimulation demonstrated enhanced rather than attenuated Epi release from the adrenal medulla (P less than 0.05 saline vs. ET treated). These results suggest that the decline in Epi following the ET-induced elevation may be mediated by a decrease in the afferent signal that initiates Epi release.
Neural and humoral effects on hindlimb vascular resistance of ducks during forced submergence
Authors: Lacombe A. M. , Jones D. R.
Published: December 2017

Circulating catecholamines increase by three orders of magnitude in forced submerged ducks; their role in promoting vascular resistance was studied using vascular perfusion of hindlimbs. Perfusion pressure and blood flow were recorded simultaneously in hindlimbs of ducks during forced submergence. One leg was perfused with blood mixtures devoid of catecholamines (test leg) and compared with the other autoperfused leg. Perfusion pressures in test legs perfused with hyperoxic and hypocapnic blood or with hypoxic and hypocapnic blood were not significantly different from those in the matching autoperfused legs. However, when test legs were perfused with hypercapnic blood, regardless of whether blood was hypoxic or hyperoxic, perfusion pressures were significantly lower than in autoperfused legs. Adding catecholamines to test legs perfused with hypoxic and hypercapnic blood, after 3 min submergence, significantly enhanced vasoconstriction. Hypercapnia acts directly on the peripheral vascular beds and impairs the neurally mediated vasoconstriction during submergence, while circulating catecholamines restore peripheral vasoconstriction. Thus circulating catecholamines are needed to compensate for the depressant action of hypercapnia on neurally mediated vasoconstriction.
Modulation of bradykinin-induced gastric-cardiovascular reflexes by histamine
Authors: Stebbins C. L. , Stahl G. L. , Theodossy S. J. , Longhurst J. C.
Published: December 2017

Both histamine and bradykinin induce gastric-cardiovascular reflexes and are released during several pathophysiological conditions. This study examined the possibility that histamine modulates the magnitude of the reflex response to stimulation by bradykinin. Thus in chloralose anesthetized cats, the cardiovascular response to stimulation of the gastric serosa with 1 microgram/ml bradykinin was monitored before and after topical application of 100 micrograms/ml histamine (n = 6) or 1 mg/ml diphenhydramine (H1-receptor antagonist) and histamine (n = 5). After application of histamine, bradykinin-induced increases in mean arterial pressure and left ventricular pressure were attenuated by 23 and 27%, respectively. Conversely, when the H1-receptors on the serosal surface of the stomach were blocked (n = 5) before application of histamine, the pressor response to bradykinin was augmented by 26%. To determine the afferents that might contribute to the attenuating effect of histamine, we recorded single unit activity in 14 A delta and 21 C visceral afferent fibers in response to bradykinin stimulation before and after histamine stimulation. We observed that the impulse activity of 10 of the A delta and 14 of the C fibers to bradykinin stimulation was reduced after treatment with histamine. These results suggest that histamine induces an inhibitory effect on the nerve endings of visceral A delta and C fibers to the action of bradykinin through an H1-receptor mechanism. This inhibitory effect attenuates the magnitude of the consequent cardiovascular reflex response.
Endothelin-1 potentiation of angiotensin II stimulation of aldosterone production
Authors: Cozza E. N. , Chiou S. , Gomez-Sanchez C. E.
Published: December 2017

Endothelin-1 (ET-1) binds to specific receptors in cultured bovine adrenal glomerulosa cells and stimulates aldosterone secretion with a 50% effective concentration (EC50) of 300 +/- 80 pM (mean +/- SE). The relative stimulatory potency for ET-1 is significantly less than that of angiotensin II (ANG II). The incubation of calf zona glomerulosa cells in primary culture with ET-1 and ANG II resulted in a significant potentiation of ANG II effect on aldosterone secretion. The EC50 of ET-1 potentiation of ANG II-induced stimulation of aldosterone secretion was 40 +/- 5 pM (mean +/- SE, n = 4), which is lower than the EC50 for ET-1 stimulation of aldosterone secretion. Adrenocorticotropic hormone (ACTH) stimulation of aldosterone secretion, but not that of potassium, was also potentiated by ET-1, but to a lesser degree. ET-1 and ET-1-mediated potentiation of ANG II-stimulated aldosterone biosynthesis increased both the early and late pathways of aldosterone biosynthesis, but the potentiation was greater for the early pathway. Preincubation with ET-1 for at least 15 min, followed by extensive washing to remove bound ET-1, also resulted in persistent potentiation of ANG II-mediated aldosterone secretion. ET-2, sarafotoxin, and vasoactive intestinal contractor potentiation of ANG II action were very similar to that of ET-1. ET-3 and Big-ET-1 potentiated ANG II stimulation only at the highest doses tested and the proendothelin-(110-130) fragment was inactive. ET-1 potentiation of ANG II action is likely to be mediated through an ETB receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)
Patterns of hemodynamic responses associated with central activation of coronary vasoconstriction
Authors: Jones L. F. , Gutterman D. D. , Brody M. J.
Published: December 2017

Previous studies in our laboratory have identified several central sites from which coronary vasoconstriction can be elicited by electrical stimulation. The present study was conducted to determine if specific patterns of hemodynamic responses are associated with activation of the coronary vasoconstrictor pathway in the hypothalamus, pons, and medulla. Cats anesthetized with chloralose were instrumented for recording arterial pressure, heart rate, and coronary, femoral, renal, and mesenteric blood flow velocities. After vagotomy and atenolol (1 mg/kg iv), anterior hypothalamus (AHA), parabrachial nucleus (PBN), a site very close to the ventral surface of the pons lateral to the pyramidal tract, and rostral ventrolateral medulla (RVLM) were stimulated electrically. Stimulation produced a decrease in coronary blood flow that was associated with all of the cardiovascular components of the defense reaction, an integrated response that included a decrease in hindquarter vascular resistance (blocked by methyl atropine), increases in renal and mesenteric vascular resistances, and a pressor response, except no change in renal vascular resistance from RVLM. Different patterns of hemodynamic responses were obtained from sites outside the coronary vasoconstrictor areas. From these results we conclude that coronary vasoconstriction is a frequent component of the defense reaction.
Angiotensin-related intakes of water and NaCl in Fischer 344 and Sprague-Dawley rats
Authors: Caputo F. A. , Rowland N. E. , Fregly M. J.
Published: December 2017

Rats of the Fischer 344 (F344) strain drank less water after either peripheral or central acute administration of angiotensin III (ANG III) than rats of the Sprague-Dawley (SD) strain. In contrast, water intakes following acute administration of ANG II were comparable in the two strains. Chronic peripheral administration of ANG II produced a salt appetite in SD but not in F344 rats; ANG III was ineffective in both strains. These data suggest that some aspects of responsiveness to ANG peptides are reduced in F344 rats. In two of three studies, water intake after acute peripheral administration of either ANG I or the beta-adrenergic agonist isoproterenol did not differ between strains; in one study, the response to both dipsogens was lower in F344 rats. Plasma renin activity was elevated to the same level by isoproterenol in both strains of rats. These results suggest that the ability of isoproterenol to release renin, the subsequent generation of ANG I, and the conversion to ANG II are similar in the two strains. However, this similarity did not extend to cardiovascular responses. Rats of the F344 strain showed a smaller decrease in blood pressure following administration of isoproterenol than did those of the SD strain. Whether this is related to differences in either the regulation of beta-adrenoreceptors or postreceptor effects in vascular smooth muscle between strains will require additional investigation.
Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia
Authors: Ng E. H. , Rock C. S. , Lazarus D. D. , Stiaino-Coico L. , Moldawer L. L. , Lowry S. F.
Published: December 2017

Insulin-like growth factor I (IGF-I) has been implicated in the regulation and maintenance of skeletal muscle protein balance and thus may be of potential benefit in attenuating the cancer-cachectic process. To examine this hypothesis, 47 sham or tumor-implanted Fischer 344 rats were randomized to receive either continuous subcutaneous IGF-I (220 or 400 micrograms/day) or saline as control. In the tumor-bearing (TB) population, IGF-I-treated groups showed a dose-dependent increase in host weight gain (P less than 0.05), final carcass weight (P less than 0.05), and gastrocnemius muscle weights (P less than 0.05) and protein contents (0.50 +/- 0.02, 0.40 +/- 0.01, and 0.52 +/- 0.03 g/100 g host wt, for non-TB saline, TB saline, and TB 400 mg IGF-I groups, respectively; P less than 0.01, IGF-I vs. saline). Similar increases in muscle RNA and DNA contents (P less than 0.01) were induced by IGF-I treatment (P less than 0.05). IGF-I treatment in this rat sarcoma model significantly reduced the proportion of aneuploid cells in the tumor (aneuploid-to-diploid ratio: TB saline 1.1 +/- 0.2 vs. TB IGF-I 0.5 +/- 0.1; P less than 0.05). IGF-I treatment attenuated host muscle protein and lean tissue depletion without stimulation of tumor growth. The tumor aneuploid population was reduced in response to IGF-I treatment. Thus IGF-I may be a potential therapeutic agent in cancer-induced cachexia.
Circadian changes of brown adipose tissue thermogenesis in juvenile rats
Authors: Redlin U. , Nuesslein B. , Schmidt I.
Published: December 2017

The aim of this study was to determine whether the circadian cycle of core temperature (Tc) and oxygen consumption (VO2) in juvenile rats is correlated with changes in the thermogenic activity of brown adipose tissue (BAT). Nine-day-old rat pups derived from two colonies with 12:12 h light-dark cycles 180 degrees out of phase were artificially reared in continuous light for 12-48 h while Tc and VO2 were recorded. For measurement of GDP binding half the pups from each colony were killed during the maximum phase of their circadian Tc cycle and the other half during the minimum phase. During the maximum phase (0.5-2 h after lights-off in the colony of origin), when Tc was 36.1 +/- 0.1 degrees C, GDP binding (pmol/mg protein) was 575 +/- 31 (n = 19). During the minimum phase (0.5-2 h after lights-on), when Tc was 32.9 +/- 0.5 degrees C, GDP binding was 361 +/- 47 (n = 19). Moreover, the correlations between Tc, VO2, and GDP binding determined during the maximum plateau of the circadian cycle differ substantially from those determined during the minimum phase. Consequently, developmental studies of thermoregulation and BAT activity in suckling pups are seriously compromised if circadian phase is neglected.
Age and gender effects on insulin secretion and glucose sensitivity of the endocrine pancreas
Authors: Ruhe R. C. , Curry D. L. , Herrmann S. , McDonald R. B.
Published: December 2017

Glucose-stimulated insulin secretion was evaluated in whole perfused pancreases and islets of Langerhans (90 to 110 microns diam) isolated from female and male Fischer 344 (F344) rats aged 6, 12, and 26 mo. Total glucose-stimulated (11.1 mmol/l) insulin release of whole perfused pancreases from male rats did not differ among age groups. In contrast, insulin secretion of 26-mo-old female rats was significantly greater than 6- and 12-mo-old female rats. Insulin secretion by islets of Langerhans incubated in glucose concentrations of 11.1, 16.7, and 22.2 mmol/l was greater in male rats compared with age-matched female animals at all three ages, and was greater in 6-vs. 26-mo-old male rats. Insulin secretion of female rats revealed some significant differences among the age groups, although no clear pattern was evident. Sensitivity of the islets to glucose was estimated from the rate of glucose oxidation. At incubation medium glucose concentrations of 11.1 mmol/l or higher, no effect of gender was observed, although the glucose oxidation rate of islets from male 26-mo-old rats was greater than that of islets from gender-matched 6-mo-old rats. These data indicate that in both the whole perfused pancreas and isolated islets of Langerhans, glucose-stimulated insulin secretion is not significantly altered with age or gender in the F344 rat. However, it appears that maintenance of insulin secretory capacity by aging male rats is achieved by enhancement of beta-cell sensitivity to glucose.
Downregulation of sodium channels during anoxia: a putative survival strategy of turtle brain
Authors: Perez-Pinzon M. A. , Rosenthal M. , Sick T. J. , Lutz P. L. , Pablo J. , Mash D.
Published: December 2017

In contrast to mammalian brain, which exhibits rapid degeneration during anoxia, the brains of certain species of turtles show an extraordinary capacity to survive prolonged anoxia. The decrease in energy expenditure shown by the anoxic turtle brain is likely to be a key factor for anoxic survival. The "channel arrest" hypothesis proposes that ion channels, which regulate brain electrical activity in normoxia, may be altered during anoxia in the turtle brain as a mechanism to spare energy. Goals of present research were to test this hypothesis and to determine whether down-regulation of sodium channels is a possible explanation for spike threshold shifts seen during anoxia in isolated turtle cerebellum. We report here that anoxia induced a significant (42%) decline in voltage-gated sodium channel density as determined by studies of the binding of a sodium channel ligand, [3H]brevetoxin. This study demonstrates that sodium channel densities in brain may be regulated by tissue oxygenation or by physiological events associated with anoxia. Moreover, it also suggests that downregulation of sodium channels may be a basis for changes in action potential thresholds, the electrical depression and energy conservation that provide the unique anoxic tolerance of turtle brain.