bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular reactivity and baroreflex function during hyperthermia in conscious rats
Authors: Massett Michael P. , Lewis Stephen J. , Stauss Harald M. , Kregel Kevin C.
Published: December 2017

The hemodynamic responses to vasoconstrictor agents are blunted during heating in anesthetized rats. It is unknown whether reflex neural responses to these agents are also altered during hyperthermia. Therefore, the purpose of this study was to determine the effect of hyperthermia on the hemodynamic and baroreflex-mediated sympathetic neural responses to vasoactive agents in conscious, unrestrained rats. The splanchnic sympathetic nerve activity (SpNA) and systemic and regional hemodynamic responses to injections of phenylephrine and sodium nitroprusside were measured during normothermia (37°C) and hyperthermia (41.5°C). The hemodynamic responses to phenylephrine and sodium nitroprusside were blunted with heating, whereas the SpNA responses to both agents were augmented or unchanged. At 41.5°C, the baroreflex curves relating heart rate (HR) and SpNA to mean arterial blood pressure were shifted to the right. The operating range and gain of the blood pressure (BP)-HR reflex were significantly reduced during heating, whereas the operating range of the BP-SpNA reflex was augmented at 41.5°C. These results indicate that heating alters the cardiovascular and sympathetic neural responses to vasoactive agents in vivo. Furthermore, the data suggest that heating differentially affects arterial baroreflex control of HR and SpNA, shifting both curves toward higher BP values but selectively attenuating baroreflex control of HR.
Circadian rhythm changes in core temperature over the menstrual cycle: method for noninvasive monitoring
Authors: Coyne Mary D. , Kesick Christina M. , Doherty Tammy J. , Kolka Margaret A. , Stephenson Lou A.
Published: December 2017

The purpose of this study was to determine whether core temperature (Tc) telemetry could be used in ambulatory women to track changes in the circadian Tc rhythm during different phases of the menstrual cycle and, more specifically, to detect impending ovulation. Tcwas measured in four women who ingested a series of disposable temperature sensors. Data were collected each minute for 2–7 days and analyzed in 36-h segments by automated cosinor analysis to determine the mesor (mean temperature), amplitude, period, acrophase (time of peak temperature), and predicted circadian minimum core temperature (Tc-min) for each cycle. The Tcmesor was higher ( P ≤ 0.001) in the luteal (L) phase (37.39 ±0.13°C) and lower in the preovulatory (P) phase (36.91 ±0.11°C) compared with the follicular (F) phase (37.08 ±0.13°C). The predicted Tc-min was also greater in L (37.06 ± 0.14°C) than in menses (M; 36.69 ± 0.13°C), F (36.6 ± 0.16°C), and P (36.38 ± 0.08°C) ( P ≤ 0.0001). During P, the predicted Tc-min was significantly decreased compared with M and F ( P ≤ 0.0001). The amplitude of the Tc rhythm was significantly reduced in L compared with all other phases ( P ≤ 0.005). Neither the period nor acrophase was affected by menstrual cycle phase in ambulatory subjects. The use of an ingestible temperature sensor in conjunction with fast and accurate cosinor analysis provides a noninvasive method to mark menstrual phases, including the critical preovulatory period.
Comparison of the effects of sucrose and fructose on insulin action and glucose tolerance
Authors: Thresher Jeffrey S. , Podolin Deborah A. , Wei Yuren , Mazzeo Robert S. , Pagliassotti Michael J.
Published: December 2017

The purpose of the present study was to determine whether fructose is the nutrient mediator of sucrose-induced insulin resistance and glucose intolerance. Toward this end, male rats were fed a purified starch diet (68% of total calories) for a 2-wk baseline period. After this, rats either remained on the starch (ST) diet or were switched to a sucrose (SU, 68% of total calories), fructose/glucose (F/G, 34/34% of total calories), or fructose/starch (F/ST, 34/34% of total calories) diet for 5 wk. Rats then underwent either an intravenous glucose tolerance test ( n = 10/diet) or a euglycemic, hyperinsulinemic clamp ( n = 8 or 9/diet). Incremental glucose and insulin areas under the curve in SU, F/G, and F/ST were on average 61 and 29% greater than ST, respectively, but not significantly different from one another. During clamps, glucose infusion rates (mg · kg−1 · min−1) required to maintain euglycemia were significantly lower ( P< 0.05) in SU, F/G, and F/ST (13.4 ± 0.9, 9.5 ± 1.7, 11.3 ± 1.3, respectively) compared with ST (22.8 ± 1.1). Insulin suppression of glucose appearance (mg · kg−1 · min−1) was significantly lower ( P < 0.05) in SU, F/G, and F/ST (5.6 ± 0.5, 2.2 ± 1.2, and 6.6 ± 0.7, respectively) compared with ST (9.6 ± 0.4). Insulin-stimulated glucose disappearance (mg · kg−1 · min−1) was significantly lower ( P < 0.05) in SU, F/G, and F/ST (17.9 ± 0.6, 16.2 ± 1.3, 15.3 ± 1.8, respectively) compared with ST (24.7 ± 1.2). These data suggest that fructose is the primary nutrient mediator of sucrose-induced insulin resistance and glucose intolerance.
Contribution of central ANG II to acute stress-induced changes in baroreflex function in young rats
Authors: Porter James P.
Published: December 2017

The aim of the present investigation was to characterize the baroreflex in weaned 23- to 25-day-old rats when maternal influences were no longer present. The relationship between mean arterial pressure (MAP) and heart rate (HR) was determined during baroreceptor loading with phenylephrine and baroreceptor unloading with sodium nitroprusside in conscious rats, first in the freely moving state and subsequently during acute stress. In unstressed rats, the slope of the relationship between MAP and HR was greater during baroreceptor loading than baroreceptor unloading. Acute stress significantly attenuated the slope of the response to baroreceptor loading but increased the slope of the response to baroreceptor unloading. Pretreatment with intracerebroventricular or intravenous losartan, an AT1 receptor antagonist, or intracerebroventricular α-helical corticotropin-releasing hormone (α-hCRH), a receptor antagonist, before the stress significantly reduced the stress-induced attenuation of slope during baroreceptor loading. Hence, young postweaning rats can alter baroreflex function during acute stress in a manner that would favor increases in MAP. Even at this young age, a central action of ANG II and CRH contributes to these stress-induced adaptations.
Cardiovascular and metabolic responses of hypertensive and normotensive rats to one week of cold exposure
Authors: Chambers J. B. , Williams T. D. , Nakamura A. , Henderson R. P. , Overton J. M. , Rashotte M. E.
Published: December 2017

Challenges to energy homeostasis, such as cold exposure, can have consequences for both metabolic and cardiovascular functioning. We hypothesized that 1-wk cold exposure (4°C) would produce concurrent increases in metabolic rate (V˙o2; indirect calorimetry), heart rate (HR), and mean arterial blood pressure (MAP) measured by telemetry. In the initial hours of change in ambient temperature (Ta), both spontaneously hypertensive rats (SHRs) and normotensive Sprague-Dawley rats showed rapid increases (in cold) or decreases (in rewarming) of V˙o2, HR, and MAP, although the initial changes in MAP and HR were more exaggerated in SHRs. Throughout cold exposure, HR,V˙o2, food intake, and locomotor activity remained elevated but MAP decreased in both strains, particularly in the SHR. During rewarming, all measures normalized quickly in both strains except MAP, which fell below baseline (hypotension) for the first few days. The results indicate that variations of Taproduce rapid changes in a suite of cardiovascular and behavioral responses that have many similarities in hypertensive and normotensive strains of rats. The findings are consistent with the general concept that the cardiovascular responses to cold exposure in rats are closely related to and perhaps a secondary consequence of the mechanisms responsible for increasing heat production.
Expression of members of the multidrug resistance protein family in human term placenta
Authors: St-Pierre M. V. , Serrano M. A. , Macias R. I. R. , Dubs U. , Hoechli M. , Lauper U. , Meier P. J. , Marin J. J. G.
Published: December 2017

The placenta serves, in part, as a barrier to exclude noxious substances from the fetus. In humans, a single-layered syncytium of polarized trophoblast cells and the fetal capillary endothelium separate the maternal and fetal circulations. P-glycoprotein is present in the syncytiotrophoblast throughout gestation, consistent with a protective role that limits exposure of the fetus to hydrophobic and cationic xenobiotics. We have examined whether members of the multidrug resistance protein (MRP) family are expressed in term placenta. After screening a placenta cDNA library, partial clones of MRP1, MRP2, and MRP3 were identified. Immunofluorescence and immunoblotting studies demonstrated that MRP2 was localized to the apical syncytiotrophoblast membrane. MRP1 and MRP3 were predominantly expressed in blood vessel endothelia with some evidence for expression in the apical syncytiotrophoblast. ATP-dependent transport of the anionic substrates dinitrophenyl-glutathione and estradiol-17-β-glucuronide was also demonstrated in apical syncytiotrophoblast membranes. Given the cellular distribution of these transporters, we hypothesize that MRP isoforms serve to protect fetal blood from entry of organic anions and to promote the excretion of glutathione/glucuronide metabolites in the maternal circulation.
Angiotensin-converting enzyme inhibitor inhibits dehydration-enhanced fever induced by endotoxin in rats
Authors: Watanabe Tatsuo , Hashimoto Makoto , Wada Minoru , Imoto Toshiaki , Miyoshi Michio , Sadamitsu Daikai , Maekawa Tsuyoshi
Published: December 2017

It has been reported that a host develops a marked fever under dehydrated conditions compared with normally hydrated conditions (11). The present study was carried out to investigate whether ANG II is involved in the enhancement seen in dehydrated rats of the fever induced by bacterial endotoxin. The results showed that intravenous injection of bacterial endotoxin produced a fever in dehydrated rats (rats deprived of water for 24 h) that was significantly greater than that seen in normally hydrated rats. In contrast, dehydration had no effect on the fever induced by intravenous interleukin-1β (IL-1β). Under dehydrated conditions, the enhanced endotoxin-induced fever was significantly inhibited by the angiotensin-converting enzyme inhibitor lisinopril, but the IL-1β fever was not. These results suggest that the dehydration-induced enhancement of endotoxin fever is due, at least in part, to the action of ANG II, which elicits an increased production of pyrogenic cytokines such as IL-1.
Neural control of the kidney: functionally specific renal sympathetic nerve fibers
Authors: DiBona Gerald F.
Published: December 2017

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs via mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers in addition to an innervation that is shared among all the effectors. This arrangement permits the maximum flexibility in the coordination of physiologically appropriate responses of the tubules, the blood vessels, and the juxtaglomerular granular cells to a variety of homeostatic requirements.
Oxygen limitation of thermal tolerance defined by cardiac and ventilatory performance in spider crab,Maja squinado
Authors: Frederich Markus , Pörtner Hans O.
Published: December 2017

Geographic distribution limits of ectothermal animals appear to be correlated with thermal tolerance thresholds previously identified from the onset of anaerobic metabolism. Transition to these critical temperatures was investigated in the spider crab ( Maja squinado) with the goal of identifying the physiological processes limiting thermal tolerance. Heart and ventilation rates as well as Po2in the hemolymph were recorded on-line during progressive temperature change between 12 and 0°C (1°C/h) and between 12 and 40°C (2°C/h). Lactate and succinate were measured in tissues and hemolymph after intermediate or final temperatures were reached. High levels of hemolymph oxygenation suggest that an optimum range of aerobic performance exists between 8 and 17°C. Thermal limitation may already set in at the transition from optimum to pejus (pejus = turning worse, progressively deleterious) range, characterized by the onset of a decrease in arterial Po2due to reduced ventilatory and cardiac performance. Hemolymph Po2values fell progressively toward both low and high temperature extremes until critical temperatures were reached at ∼1 and 30°C, as indicated by low Po2and the onset of anaerobic energy production by mitochondria. In conclusion, the limited capacity of ventilation and circulation at extreme temperatures causes insufficient O2supply, thereby limiting aerobic scope and, finally, thermal tolerance.
HSP72 as a complementary protection against oxidative stress induced by exercise in the soleus muscle of rats
Authors: Smolka Marcus B. , Zoppi Claudio C. , Alves Armindo A. , Silveira Leonardo R. , Marangoni Sergio , Pereira-Da-Silva Lucia , Novello José C. , Macedo Denise V.
Published: December 2017

Given the potential of reactive oxygen species to damage intracellular proteins during subsequent bouts of muscle contractions, it was suggested that, when this production exceeds the antioxidant capacity, the preexisting antioxidant pathways may be complemented by the synthesis of the defense mechanism represented by heat shock proteins (HSPs), stress proteins with the function of repair and maintaining protein folding. To test this hypothesis, we analyzed reactive carbonyl derivatives in plasma and the expression of HSP72 and activities of enzymes from the oxidative and antioxidant defense systems in the soleus muscle of sedentary rats and rats trained by two protocols: continuous and intermittent. We analyzed all three groups at rest and 2 h after acute exercise. After 8 wk of training, the animals from both groups clearly demonstrated higher resistance to exercise. Both trained groups showed significantly higher citrate synthase, catalase, and glutathione reductase activities than the control group ( P < 0.01). After acute exercise, catalase and glutathione reductase activities significantly decreased ( P < 0.01) and plasma reactive carbonyl derivatives significantly increased ( P < 0.05) in the sedentary group, suggesting an oxidative-stress condition as responsible for exhaustion in this group. Finally, after acute exercise, the induction of HSP72 expression occurred only in the sedentary group, suggesting that HSP72 acts as a complementary protective mechanism in exercise-induced oxidative stress.
Role of cyclooxygenase-2-derived metabolites and nitric oxide in regulating renal function
Authors: Llinás María T. , Rodríguez Francisca , Moreno Carol , Salazar F. Javier
Published: December 2017

The aim of this study was to examine the relative contribution of both cyclooxygenase (COX) isoforms in producing the prostaglandins (PG) involved in the regulation of renal function, when nitric oxide (NO) synthesis is reduced. In anesthetized dogs with reduction of NO synthesis, the renal effects of a nonisozyme-specific COX inhibitor (meclofenamate) were compared with those elicited by a selective COX-2 inhibitor (nimesulide) before and during an extracellular volume expansion (ECVE). Intrarenal NG- nitro-l-arginine methyl ester (l-NAME) infusion (1 μg · kg−1· min−1; n = 6) did not elicit renal hemodynamic changes and reduced ( P < 0.01) the renal excretory response to ECVE. Intravenous nimesulide (5 μg · kg−1· min−1; n = 6) did not modify renal hemodynamic and reduced ( P < 0.05) sodium excretion before ECVE. Simultaneousl-NAME and nimesulide infusion ( n = 7) elicited an increment (37%) in renal vascular resistance (RVR; P < 0.05) before ECVE and no hemodynamic changes during ECVE. The reduced excretory response elicited byl-NAME and nimesulide was similar to that found duringl-NAME infusion. Finally, simultaneous l-NAME and meclofenamate infusion (10 μg · kg−1· min−1; n = 7) induced an increase in RVR (91%, P < 0.05), a decrease in glomerular filtration rate (35%, P < 0.05), and a reduction of the renal excretory response to ECVE that was greater ( P < 0.05) than that elicited by l-NAME alone. The results obtained support the notion that PG involved in regulating renal hemodynamic and excretory function when NO synthesis is reduced are mainly dependent on COX-1 activity.
Potassium channels in primary cultures of seawater fish gill cells. I. Stretch-activated K+channels
Authors: Duranton C. , Mikulovic E. , Tauc M. , Avella M. , Poujeol P.
Published: December 2017

Previous studies using the patch-clamp technique demonstrated the presence of a small conductance Cl−channel in the apical membrane of respiratory gill cells in primary culture originating from sea bass Dicentrarchus labrax. We used the same technique here to characterize potassium channels in this model. A K+channel of 123 ± 3 pS was identified in the cell-attached configuration with 140 mM KCl in the bath and in the pipette. The activity of the channel declined rapidly with time and could be restored by the application of a negative pressure to the pipette (suction) or by substitution of the bath solution with a hypotonic solution (cell swelling). In the excised patch inside-out configuration, ionic substitution demonstrated a high selectivity of this channel for K+over Na+and Ca2+. The mechanosensitivity of this channel to membrane stretching via suction was also observed in this configuration. Pharmacological studies demonstrated that this channel was inhibited by barium (5 mM), quinidine (500 μM), and gadolinium (500 μM). Channel activity decreased when cytoplasmic pH was decreased from 7.7 to 6.8. The effect of membrane distension by suction and exposure to hypotonic solutions on K+channel activity is consistent with the hypothesis that stretch-activated K+channels could mediate an increase in K+conductance during cell swelling.
Effects of exercise on mitogen- and stress-activated kinase signal transduction in human skeletal muscle
Authors: Krook Anna , Widegren Ulrika , Jiang Xin Jian , Henriksson Jan , Wallberg-Henriksson Harriet , Alessi Dario , Zierath Juleen R.
Published: December 2017

Exercise/contraction is a powerful stimulator of mitogen-activated protein (MAP) kinase cascades in skeletal muscle. Little is known regarding the physiological activation of enzymes downstream of MAP kinase. We investigated whether acute exercise results in activation of mitogen- and stress-activated kinases (MSK) 1 and 2, p90 ribosomal S6 kinase (p90rsk), and MAP kinase-activated protein kinase 2 (MAPKAPK2). Muscle biopsies were obtained from healthy volunteers before, during, and after 60 min one-leg cycle ergometry, from exercising and resting legs. MSK1 and MSK2 activities were increased 400–500% and 200–300%, respectively, in exercised muscle ( P < 0.05 vs. rest). A dramatic increase in activity of p90rsk (MAPKAPK1) (>2,500%), and to a lesser extent MAPKAP2 (300%), was noted with exercise ( P < 0.05 vs. rest). MSK1, MSK2, p90rsk, and MAPKAP2 activities were sustained throughout exercise. Exercise-induced activation of these enzymes was limited to working muscle, indicating that local rather than systemic factors activate these signaling cascades. Thus physical exercise leads to activation of multiple enzymes downstream of MAP kinase.
Sympathetic activity in early renal posttransplantation hypertension in rats
Authors: Grisk Olaf , Frey Bernd A. J. , Uber Andreas , Rettig Rainer
Published: December 2017

The contribution of elevated sympathetic activity to the development of renal posttransplantation hypertension was investigated. F1 hybrids (F1H) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were transplanted with either an SHR or an F1H kidney and bilaterally nephrectomized. Three weeks after transplantation, sympathetic activity was assessed by measuring adrenal tyrosine hydroxylase (TH) mRNA content and recording splanchnic nerve activity (SNA) in conscious animals. To investigate the dependence of arterial pressure on sympathetic activity, animals were treated with the α2-adrenoceptor agonist guanabenz intracerebroventricularly. Mean arterial pressure (MAP) was 143 ± 4 mmHg in recipients of an SHR kidney ( n = 15) versus 110 ± 3 mmHg in recipients of an F1H kidney ( n = 10; P < 0.001). Adrenal TH mRNA content was 1.93 ± 0.15 fmol/μg total RNA in recipients of an SHR kidney versus 1.96 ± 0.17 fmol/μg total RNA in recipients of an F1H kidney (not significant). SNA did not differ significantly between recipients of an SHR kidney ( n = 8) and recipients of an F1H kidney ( n = 7) in terms of frequency and amplitude of synchronized nerve discharges. In response to cumulative intracerebroventricular administration of 10 and 20 μg guanabenz, SNA fell to 51 ± 5% of control in recipients of an SHR kidney versus 44 ± 6% of control in recipients of an F1H kidney (not significant) accompanied by a slight fall in MAP in either group. The results suggest that elevated sympathetic activity is not a major contributor to the development of renal posttransplantation hypertension.
Different adrenal sympathetic preganglionic neurons regulate epinephrine and norepinephrine secretion
Authors: Morrison Shaun F. , Cao Wei-Hua
Published: December 2017

Brain stimulation or activation of certain reflexes can result in differential activation of the two populations of adrenal medullary chromaffin cells: those secreting either epinephrine or norepinephrine, suggesting that they are controlled by different central sympathetic networks. In urethan-chloralose-anesthetized rats, we found that antidromically identified adrenal sympathetic preganglionic neurons (SPNs) were excited by stimulation of the rostral ventrolateral medulla (RVLM) with either a short (mean: 29 ms) or a long (mean: 129 ms) latency. The latter group of adrenal SPNs were remarkably insensitive to baroreceptor reflex activation but strongly activated by the glucopenic agent 2-deoxyglucose (2-DG), indicating their role in regulation of adrenal epinephrine release. In contrast, adrenal SPNs activated by RVLM stimulation at a short latency were completely inhibited by increases in arterial pressure or stimulation of the aortic depressor nerve, were unaffected by 2-DG administration, and are presumed to govern the discharge of adrenal norepinephrine-secreting chromaffin cells. These findings of a functionally distinct preganglionic innervation of epinephrine- and norepinephrine-releasing adrenal chromaffin cells provide a foundation for identifying the different sympathetic networks underlying the differential regulation of epinephrine and norepinephrine secretion from the adrenal medulla in response to physiological challenges and experimental stimuli.
Renal nerve inhibition by central NaCl and ANG II is abolished by lesions of the lamina terminalis
Authors: May C. N. , McAllen R. M. , McKinley M. J.
Published: December 2017

The lamina terminalis is situated in the anterior wall of the third ventricle and plays a major role in fluid and electrolyte homeostasis and cardiovascular regulation. The present study examined whether the effects of intracerebroventricular infusion of hypertonic saline and ANG II on renal sympathetic nerve activity (RSNA) were mediated by the lamina terminalis. In control, conscious sheep ( n = 5), intracerebroventricular infusions of 0.6 M NaCl (1 ml/h for 20 min) and ANG II (10 nmol/h for 30 min) increased mean arterial pressure (MAP) by 6 ± 1 ( P < 0.001) and 14 ± 3 mmHg ( P < 0.001) and inhibited RSNA by 80 ± 6 ( P < 0.001) and 89 ± 7% ( P < 0.001), respectively. Both treatments reduced plasma renin concentration (PRC). Intracerebroventricular infusion of artificial cerebrospinal fluid (1 ml/h for 30 min) had no effect. In conscious sheep with lesions of the lamina terminalis ( n = 6), all of the responses to intracerebroventricular hypertonic saline and ANG II were abolished. In conclusion, the effects of intracerebroventricular hypertonic saline and ANG II on RSNA, PRC, and MAP depend on the integrity of the lamina terminalis, indicating that this site plays an essential role in coordinating the homeostatic responses to changes in brain Na+ concentration.
Inhibition of poly(ADP-ribose) polymerase attenuates ischemic renal injury in rats
Authors: Martin Daniel R. , Lewington Andrew J. P. , Hammerman Marc R. , Padanilam Babu J.
Published: December 2017

The enzyme, poly(ADP-ribose) polymerase (PARP), effects repair of DNA after ischemia-reperfusion (I/R) injury to cells in nerve and muscle tissue. However, its activation in severely damaged cells can lead to ATP depletion and death. We show that PARP expression is enhanced in damaged renal proximal tubules beginning at 6–12 h after I/R injury. Intraperitoneal administration of PARP inhibitors, benzamide or 3-amino benzamide, after I/R injury accelerates the recovery of normal renal function, as assessed by monitoring the levels of plasma creatinine and blood urea nitrogen during 6 days postischemia. PARP inhibition leads to increased cell proliferation at 1 day postinjury as assessed by proliferating cell nuclear antigen and improves the histopathological appearance of kidneys examined at 7 days postinjury. Furthermore, inhibition of PARP increases levels of ATP measured at 24 h postischemia compared with those in vehicle-treated animals. Our data indicate that PARP activation is a part of the cascade of molecular events that occurs after I/R injury in the kidney. Although caution is advised, transient inhibition of PARP postischemia may constitute a novel therapy for acute renal failure.
A developmental switch affecting growth of fatty rats
Authors: Truett Gary E. , Walker Jerilyn A. , Harris Ruth B. S.
Published: December 2017

Fatty ( fa/ fa) rats accumulate more adipose mass than their littermates soon after birth, but they first appear obese during the fourth week of life. We analyzed the effects of fagenotype on growth of pups housed with their dams through 4 wk of age. The fa genotype effects on daily gain were undetectable from 7 to 22 days of age but became highly significant ( P = 10−18) at 23 days of age. When litters were reduced to 4 pups, fa genotype effects on daily gain also became detectable at 23 days of age. The fa genotype effects on daily gain, stomach contents weight, liver weight, and plasma insulin of rats killed from 20 to 24 days of age displayed a marked genotype by age interaction, becoming highly significant at 23 days of age. These changes occur without the environmental changes induced by separating pups from their dams. These observations suggest that a developmental switch triggers hyperphagia and rapidly increases growth rate of fatty rats after 22 days of age.
Benzolamide, acetazolamide, and signal transduction in avian intrapulmonary chemoreceptors
Authors: Hempleman S. C. , Rodriguez T. A. , Bhagat Y. A. , Begay R. S.
Published: December 2017

Intrapulmonary chemoreceptors (IPC) are CO2-sensitive sensory neurons that innervate the lungs of birds, help control the rate and depth of breathing, and require carbonic anhydrase (CA) for normal function. We tested whether the CA enzyme is located intracellularly or extracellularly in IPC by comparing the effect of a CA inhibitor that is membrane permeable (iv acetazolamide) with one that is relatively membrane impermeable (iv benzolamide). Single cell extracellular recordings were made from vagal filaments in 16 anesthetized, unidirectionally ventilated mallards ( Anas platyrhynchos). Without CA inhibition, action potential discharge rate was inversely proportional to inspired Pco 2 (−9.0 ± 0.8 s−1 · lnTorr−1; means ± SE, n = 16) and exhibited phasic responses to rapid Pco 2 changes. Benzolamide (25 mg/kg iv) raised the discharge rate but did not alter tonic IPC Pco 2 response (−9.8 ± 1.6 s−1 · lnTorr−1, n = 8), and it modestly attenuated phasic responses. Acetazolamide (10 mg/kg iv) raised IPC discharge, significantly reduced tonic IPC Pco 2 response to −3.5 ± 3.6 s−1 · lnTorr−1 ( n = 6), and severely attenuated phasic responses. Results were consistent with an intracellular site for CA that is less accessible to benzolamide. A model of IPC CO2 transduction is proposed.
Na+/H+exchange in mosquito Malpighian tubules
Authors: Petzel D. H.
Published: December 2017

Fluid secretion and intracellular pH were measured in isolated mosquito Malpighian tubules to determine the presence of Na+/H+exchange. Rates of fluid secretion by individual Malpighian tubules in vitro were inhibited by 78% of control in the presence of 100 μM 5-( N-ethyl- n-isopropyl)-amiloride (EIPA), a specific inhibitor of Na+/H+exchange. Steady-state intracellular pH was measured microfluorometrically by using 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in individual Malpighian tubules. Bathing the Malpighian tubules in 0 mM extracellular Na+or in the presence of 100 μM EIPA reduced the steady-state intracellular pH by 0.5 pH units. Stimulation of the Na+/H+exchanger by using the NH4Cl pulse technique resulted in a rate of recovery from the NH4Cl-induced acute acid load of 8.7 ± 1.0 × 10−3pH/s. The rates of recovery of intracellular pH after the acute acid load in the absence of extracellular Na+or in the presence of 100 μM EIPA were 0.7 ± 0.6 and −0.3 ± 0.3 × 10−3pH/s, respectively. These results indicate that mosquito Malpighian tubules possess a Na+/H+exchanger.
Insulin prolongs the QTc interval in humans
Authors: Gastaldelli Amalia , Emdin Michele , Conforti Fabrizio , Camastra Stefania , Ferrannini Ele
Published: December 2017

Insulin hyperpolarizes plasma membranes; we tested whether insulin affects ventricular repolarization. In 35 healthy volunteers, we measured the Q-T interval during electrocardiographic monitoring in the resting state and in response to hyperinsulinemia (euglycemic 1-mU · min−1 · kg−1 insulin clamp). A computerized algorithm was used to identify T waves; Bazett's formula was employed to correct Q-T (QTc) by heart rate (HR). In the resting state, QTc was inversely related to indexes of body size (e.g., body surface area, r = −0.53, P= 0.001) but not to indexes of body fatness. During the clamp, HR (67 ± 1 to 71 ± 1 beats/min, P< 0.0001) and plasma norepinephrine levels (161 ± 12 to 184 ± 10 pg/ml, P < 0.001) increased. QTc rose promptly and consistently, averaging 428 ± 6 ms between 30 and 100 min ( P = 0.014 vs. the resting value of 420 ± 5 ms). Fasting serum potassium (3.76 ± 0.03 mM) declined to 3.44 ± 0.03 mM during insulin. After adjustment for body size, resting QTc was directly related to fasting plasma insulin (partial r = 0.43, P = 0.01); furthermore, QTc was inversely related to serum potassium levels both in the fasting state (partial r = −0.16, P < 0.04) and during insulin stimulation (partial r = −0.47, P = 0.003). Neither resting nor clamp-induced QTc was related to insulin sensitivity. Physiological hyperinsulinemia acutely prolongs ventricular repolarization independent of insulin sensitivity. Both insulin-induced hypokalemia and adrenergic activation contribute to this effect.
Elevation of histidine decarboxylase activity in skeletal muscles and stomach in mice by stress and exercise
Authors: Ayada Kentaro , Watanabe Makoto , Endo Yasuo
Published: December 2017

The effects of different types of stress (water bathing, cold, restraint, and prolonged walking) on histidine decarboxylase (HDC) activity in masseter, quadriceps femoris, and pectoralis superficial muscles, and in the stomach were examined in mice. All of these stresses elevated gastric HDC activity. Although water bathing, in which muscle activity was slight, was sufficiently stressful to produce gastric hemorrhage and to increase gastric HDC activity, it produced no detectable elevation of HDC activity in any of the muscles examined. The other stresses all elevated HDC activity in all three muscles. We devised two methods of restraint, one accompanied by mastication and the other not. The former elevated HDC activity in the masseter muscle, but the latter did not. These results suggest that 1) HDC activity in the stomach is an index of responses to stress, 2) the elevation of HDC activity in skeletal muscles during stress is induced partly or wholly by muscle activity and/or muscle tension, and 3) stress itself does not always induce an elevation of HDC activity in skeletal muscles.
Refeeding signal in fasting-incubating king penguins: changes in behavior and egg temperature
Authors: Groscolas R. , Decrock F. , Thil M.-A. , Fayolle C. , Boissery C. , Robin J.-P.
Published: December 2017

This study is directed toward understanding the process of feeding stimulation (“refeeding signal”) that has been suggested to operate below a body mass threshold or critical metabolic status in spontaneously fasting birds. Behavior and egg temperature (Tegg) were continuously monitored by video monitoring and biotelemetry, respectively, in fasting-incubating king penguins kept in a pen to prevent relief by the partner until spontaneous egg abandonment. Penned birds fasted 10 days more and lost 1.2 kg more than birds relieved normally by their partner, abandoning the egg about 1 wk after reaching a critical body mass. Definitive egg abandonment was preceded by transitory abandonments of progressively increasing duration during which time the birds went further and further away from their egg. There were marked interindividual differences but on average transitory abandonments began 36 ± 5 h before the definitive abandonment and were paralleled by resumption of display songs signaling the readiness of the bird to depart for feeding. Teggwas maintained at around 35.7°C during normal incubation but significantly decreased the last 2 days before egg abandonment. These changes are interpreted as reflecting a stimulation to refeed at a threshold body mass corresponding to a critical fat store depletion. Thus the fasting-incubating king penguin appears to be an interesting animal model for understanding the long-term metabolic control of feeding behavior in relation to energy status.
Improved cardiac performance after ischemia in aged rats supplemented with vitamin E and α-lipoic acid
Authors: Coombes Jeff S. , Powers Scott K. , Hamilton Karyn L. , Demirel Haydar A. , Shanely R. Andrew , Zergeroglu Murat A. , Sen Chandan K. , Packer Lester , Ji Li Li
Published: December 2017

The purpose of these experiments was to examine the effects of dietary antioxidant supplementation with vitamin E (VE) and α-lipoic acid (α-LA) on biochemical and physiological responses to in vivo myocardial ischemia-reperfusion (I-R) in aged rats. Male Fischer-334 rats (18 mo old) were assigned to either 1) a control diet (CON) or 2) a VE and α-LA supplemented diet (ANTIOX). After a 14-wk feeding period, animals in each group underwent an in vivo I-R protocol (25 min of myocardial ischemia and 15 min of reperfusion). During reperfusion, peak arterial pressure was significantly higher ( P < 0.05) in ANTIOX animals compared with CON diet animals. I-R resulted in a significant increase ( P < 0.05) in myocardial lipid peroxidation in CON diet animals but not in ANTIOX animals. Compared with ANTIOX animals, heart homogenates from CON animals experienced significantly less ( P < 0.05) oxidative damage when exposed to five different in vitro radical producing systems. These data indicate that dietary supplementation with VE and α-LA protects the aged rat heart from I-R-induced lipid peroxidation by scavenging numerous reactive oxygen species. Importantly, this protection is associated with improved cardiac performance during reperfusion.
Time-dependent physiological regulation of ovine placental GLUT-3 glucose transporter protein
Authors: Das Utpala G. , He Jing , Ehrhardt Richard A. , Hay William W. , Devaskar Sherin U.
Published: December 2017

We immunolocalized the GLUT-3 glucose transporter isoform versus GLUT-1 in the late-gestation epitheliochorial ovine placenta, and we examined the effect of chronic maternal hyperglycemia and hypoglycemia on placental GLUT-3 concentrations. GLUT-3 was limited to the apical surface of the trophoectoderm, whereas GLUT-1 was on the basolateral and apical surfaces of this cell layer and in the epithelial cells lining the placental uterine glands. GLUT-3 concentrations declined at 17–20 days of chronic hyperglycemia ( P < 0.05), associated with increased uterine and uteroplacental net glucose uptake rate, but a normal fetal glucose uptake rate was observed. Chronic hypoglycemia did not change GLUT-3 concentrations, although uterine, uteroplacental, and fetal net glucose uptake rates were decreased. Thus maternal hyperglycemia causes a time-dependent decline in the entire placental glucose transporter pool (GLUT-1 and GLUT-3). In contrast, maternal hypoglycemia decreases GLUT-1 but not GLUT-3, resulting in a relatively increased GLUT-3 contribution to the placental glucose transporter pool, which could maintain glucose delivery to the placenta relative to the fetus when maternal glucose is low.
Endothelin and nitric oxide mediate reduced myogenic reactivity of small renal arteries from pregnant rats
Authors: Gandley Robin E. , Conrad Kirk P. , McLaughlin Margaret K.
Published: December 2017

We tested the hypothesis that endothelin acting through the endothelial ETB receptor subtype and the nitric oxide (NO) pathway accounts for reduced myogenic reactivity of the renal resistance vasculature during pregnancy. Small renal arteries (100–200 μm) were isolated from virgin and midterm pregnant rats when gestational renal hyperfiltration and vasodilation are maximal in this species. Myogenic reactivity (the adjustment of arterial diameter in response to a change in transmural pressure) was assessed with a pressurized myograph system. A rapid increase in transmural pressure from 60 to 80 mmHg resulted in a 2.4% diameter increase in vessels from virgin compared with an 8.1% increase in arteries from midgestation rats ( n = 8 each, P < 0.05). Thus myogenic reactivity is markedly reduced during pregnancy. Incubation with the NO synthase inhibitors, an ETB receptor subtype antagonist (RES-701–1), the nonselective ETA/B receptor blocker (SB-209670), or endothelial removal abrogated the reduced myogenic reactivity of vessels from gravid rats without affecting myogenic reactivity in arteries from virgin animals. Thus the endothelium mediates the reduced myogenic reactivity of small renal arteries of midgestation rats most likely through the ETB receptor subtype and NO pathway.
Hemodynamic and renal effects of acute and progressive nitric oxide synthesis inhibition in anesthetized dogs
Authors: Cases Aleix , Haas John , Burnett John C. , Romero Juan Carlos
Published: December 2017

This study evaluated the effects of progressive nitric oxide (NO) inhibition in the regulation of systemic and regional hemodynamics and renal function in anesthetized dogs. The NG-nitro-l-arginine methyl ester group ( n = 9) received progressive doses of 0.1, 1, 10, and 50 μg · kg−1· min−1. Renal (RBF), mesenteric (MBF), iliac (IBF) blood flows, mean arterial pressure (MAP), pulmonary pressures, cardiac output (CO), and systemic and pulmonary vascular resistances were measured. During NG-nitro-l-arginine methyl ester infusion, MAP and systemic vascular resistances increased in a dose-dependent manner. Mean pulmonary pressure and pulmonary vascular resistances increased in both the NG-nitro-l-arginine methyl ester and the control group, but the increase was more marked in the NG-nitro-l-arginine methyl ester group during the last two infusion periods. CO decreased progressively, before any significant change in blood pressure was noticeable in the NG-nitro-l-arginine methyl ester group. IBF decreased significantly from the first NG-nitro-l-arginine methyl ester dose, whereas RBF and MBF only decreased significantly during the highest NG-nitro-l-arginine methyl ester dose. Urinary volume and sodium excretion only increased significantly in the time control group during the two last time periods. The pulmonary vasculature was more sensitive than the systemic vasculature, whereas skeletal muscle and renal vasculatures showed a greater sensitivity to the inhibition of NO production than the mesenteric vasculature. NO synthesis inhibition induces a progressive antidiuretic and antinatriuretic effect, which is partially offset by the increase in blood pressure.
Photic and nonphotic circadian phase resetting in a diurnal primate, the common marmoset
Authors: Glass J. David , Tardif Suzette D. , Clements Robert , Mrosovsky N.
Published: December 2017

Despite the considerable literature on circadian entrainment, there is little information on this subject in diurnal mammals. Contributing to this lack of understanding is the problem of separating photic from nonphotic (behavioral) phase-resetting events in diurnal species. In the present study, photic phase resetting was obtained in diurnal common marmosets held under constant dim light (DimDim; <0.5 lx) by using a 20-s pulse of bright light to minimize time available for behavioral arousal. This stimulus elicited phase advances at circadian time (CT) 18–22 and phase delays at CT9–12. Daily presentation of these 20-s pulses produced entrainment with a phase angle of ∼11 h (0 h = activity onset). Nonphotic phase resetting was obtained under DimDim with the use of a 1-h-induced activity pulse, consisting of intermittent cage agitation and water sprinkling, delivered in total darkness to minimize photic effects. This stimulus caused phase delays at CT20–24, and entrainment to a scheduled daily regimen of these pulses occurred with a phase angle of ∼0 h. These results indicate that photic and nonphotic phase-response curves (PRCs) of marmosets are similar to those of nocturnal rodents and that nonphotic PRCs are keyed to the phase of the suprachiasmatic nucleus pacemaker, not to the phase of the activity-rest cycle.
Hypoxic vasoconstriction of cyclostome systemic vessels: the antecedent of hypoxic pulmonary vasoconstriction?
Authors: Olson Kenneth R. , Russell Michael J. , Forster Malcolm E.
Published: December 2017

Hypoxic vasoconstriction (HV) is an intrinsic response of mammalian pulmonary vascular smooth muscle (VSM). In the present study, HV was examined by myography of vessel rings from three primitive vertebrates: New Zealand hagfish (NZH), Pacific hagfish (PH), and sea lamprey (SL). Hypoxia dilated pre-gill arteries (ventral aorta, afferent branchial) from all species, whereas it contracted systemic arteries [dorsal aorta (DA), efferent branchial, celiacomesenteric]. DA HV was reproducible over several days, and it could be sustained in NZH for 8 h without adverse effects. Tension was proportional to Po2, and half-maximal HV was obtained at Po2(mmHg) of 4.7 ± 0.2 (NZH), 0.8 ± 0.1 (PH), and 10.7 ± 1.9 (SL). HV did not require preconditioning (preexisting contractile stimulus) and was unaffected by elevated extracellular potassium (200 mM NZH; 80 mM SL); removal of the endothelium (NZH); or inhibitors of cyclooxygenase, lipoxygenase, cytochrome P-450 or antagonists of α-adrenergic, muscarinic, nicotinic, purinergic, or serotoninergic receptors. These results show that HV is an intrinsic feature of systemic VSM in cyclostomes and suggest that HV has been in the repertoire of VSM responses, since the origin of vertebrates. The exceptionally hardy HV in cyclostome DA may provide a useful model with which to examine both the phylogeny and mechanisms of this response.
Glial angiotensinogen regulates brain angiotensin II receptors in transgenic rats TGR(ASrAOGEN)
Authors: Monti Jan , Schinke Martina , Böhm Manfred , Ganten Detlev , Bader Michael , Bricca Giampiero
Published: December 2017

TGR(ASrAOGEN)680, a newly developed transgenic rat line with specific downregulation of astroglial synthesis of angiotensinogen, exhibits decreased brain angiotensinogen content associated with a mild diabetes insipidus and lower blood pressure. Autoradiographic experiments were performed on TGR(ASrAOGEN) (TG) and Sprague-Dawley (SD) control rats to quantify AT1 and AT2 receptor-binding sites in different brain nuclei and circumventricular organs. Dose-response curves for drinking response to intracerebroventricular injections of ANG II were compared between SD and TG rats.

In most of the regions inside the blood-brain barrier [paraventricular nucleus (PVN), piriform cortex, lateral olfactory tract (LOT), and lateral preoptic area (LPO)], AT1 receptor binding (sensitive to CV-11974) was significantly higher in TG compared with SD. In contrast, in the circumventricular organs investigated [subfornical organ (SFO) and area postrema], AT1 receptor binding was significantly lower in TG. AT2 receptors (binding sensitive to PD-123319) were detected at similar levels in the inferior olive (IO) of both strains. Angiotensin-binding sites sensitive to both CV-11974 and PD-123319 were detected in the LPO of SD rats and specifically upregulated in LOT, IO, and most notably PVN and SFO of TG. The dose-response curve for water intake after intracerebroventricular injections showed a higher sensitivity to ANG II of TG (EC50 = 3.1 ng) compared with SD (EC50 = 11.2 ng), strongly suggesting that the upregulation of AT1 receptors inside the blood-brain barrier of TG rats is functional.

Finally, we showed that downregulation of angiotensinogen synthesized by astroglial cells differentially regulates angiotensin receptor subtypes inside the brain and in circumventricular organs.
Intestinal apical amino acid absorption during development of the pig
Authors: Buddington Randal K. , Elnif Jan , Puchal-Gardiner Anna A. , Sangild Per T.
Published: December 2017

Amino acids originating from the diet are the principal metabolic fuels for the small intestine, and although the developing intestine is exposed to dramatic changes in the types and amounts of protein, there is little known about rates of amino acid absorption across the apical membrane during development. Therefore, rates of absorption were measured for five amino acids that are substrates for the acidic (aspartate), basic (lysine), neutral (leucine and methionine), and imino (proline) amino acid carriers using intact tissues from the proximal, mid-, and distal small intestines of pigs ranging in age from 90% of gestation to 42 days after birth (12 days after weaning). Rates of absorption (sum of carrier-mediated and apparent diffusion) were highest at birth (except for proline) and declined by an average of 30% during the first 24 h of suckling. There were continuing declines for leucine, methionine, and proline but not for aspartate and lysine. Due to rapid growth of the intestine, absorption capacities for all amino acids increased faster than predicted from gains in metabolic mass. Regional differences for rates of absorption were not detected until after birth, and only for aspartate and proline. Maximum rates of saturable absorption (nmol · min−1· mg tissue−1) by the midintestine increased during the last 10% of gestation, were highest at birth, and then declined. The contribution of apparent diffusion to amino acid absorption was lowest at birth, then increased after onset of suckling.