bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue spaces in rat heart, liver, and skeletal muscle in vivo
Authors: Cieslar Julie , Huang Ming-Ta , Dobson Geoffrey P.
Published: December 2017

Tissue spaces were determined in rat heart, liver, and skeletal muscle in vivo using isotopically labeled [14C]inulin. Tracer was injected into the jugular vein of pentobarbital-anesthetized male Sprague-Dawley rats. After a 30-min equilibration period, a blood sample was taken, and heart, liver, and gastrocnemius muscle were excised and immediately freeze clamped at liquid nitrogen temperatures. The extracellular inulin space was 0.209 ± 0.006 ( n = 13), 0.203 ± 0.080 ( n = 7), and 0.124 ± 0.006 (SE) ml/g wet wt tissue ( n = 8) for heart, liver, and skeletal muscle, respectively. Total tissue water was 0.791 ± 0.005 ( n = 9), 0.732 ± 0.002 ( n = 9), and 0.755 ± 0.005 ml/g wet wt tissue ( n = 10) for heart, liver, and skeletal muscle, respectively. Expressed as a percentage of total tissue water, the intracellular space was 73.6, 72.2, and 83.7% for heart, liver, and skeletal muscle, respectively. With use of 2,3-diphospho-d-glyceric acid as a vascular marker, the interstitial space was calculated by subtracting the counts in tissue due to whole blood from total tissue counts and dividing by plasma counts. The interstitial space was 18.8, 22.4, and 14.5% of total tissue water, with accompanying plasma spaces of 7.7, 5.3, and 1.8% for heart, liver, and gastrocnemius muscle, respectively. The tracer method used in this study provides a quantitative assessment of water distribution in tissues of nonnephrectomized rats that has applications for calculation of tissue ion and metabolite concentrations, gradients, and fluxes under normal and pathophysiological conditions.
Responses of mesenteric and renal blood flow dynamics to acute denervation in anesthetized rats
Authors: Abu-Amarah Isam , Ajikobi David O. , Bachelard Hélène , Cupples William A. , Salevsky Fred C.
Published: December 2017

Previous studies have shown that renal autoregulation dynamically stabilizes renal blood flow (RBF). The role of renal nerves, particularly of a baroreflex component, in dynamic regulation of RBF remains unclear. The relative roles of autoregulation and mesenteric nerves in dynamic regulation of blood flow in the superior mesenteric artery (MBF) are similarly unclear. In this study, transfer function analysis was used to identify autoregulatory and baroreflex components in the dynamic regulation of RBF and MBF in Wistar rats and young spontaneously hypertensive rats (SHR) anesthetized with isoflurane or halothane. Wistar rats showed effective dynamic autoregulation of both MBF and RBF, as did SHR. Autoregulation was faster in the kidney (0.22 ± 0.01 Hz) than in the gut (0.13 ± 0.01 Hz). In the mesenteric, but not the renal bed, the admittance phase was significantly negative between 0.25 and 0.7 Hz, and the negative phase was abrogated by mesenteric denervation, indicating the presence of an arterial baroreflex. The baroreflex was faster than autoregulation in either bed. The presence of sympathetic effects unrelated to blood pressure was inferred in both vascular beds and appeared to be stronger in the SHR than in the Wistar rats. It is concluded that a physiologically significant baroreflex operates on the mesenteric, but not the renal circulation and that blood flow in both beds is effectively stabilized by autoregulation.
Increased cerebral infarction by cyclic flow reductions: studies in the guinea pig MCA thrombosis model
Authors: Kawano Ken-Ichi , Ikeda Yasuhiko , Kondo Kazunao , Umemura Kazuo
Published: December 2017

We have developed a photochemical model of thrombotic middle cerebral artery (MCA) occlusion in the guinea pig for investigating factors contributing to the development of cerebral infarction. In this model, cyclic flow reductions (CFRs) after recanalization of the MCA are a common observation and might contribute to the development of cerebral infarction. Therefore, we sought to measure the time course of recanalization of the guinea pig MCA after the artery had been occluded by a thrombus. Thrombotic occlusion of the MCA was induced by photochemical reaction between intravenously administered rose bengal and transluminal green light for 10, 15, 20, or 30 min. After the thrombotic occlusion of MCA and subsequent spontaneous thrombolysis, blood flow in the MCA gradually recovered to preocclusion level but with frequent CFRs. The recovery of MCA blood flow or duration of CFRs was dependent on the duration of photochemical reaction (extent of endothelial injury); thus, for a 30-min photochemical reaction, CFRs were still observed 24 h after photochemical reaction. In separate experiments, we also investigated the effect of permanent occlusion of the MCA, which was induced by electrocoagulation in the vessel on cerebral infarction. The infarct volume in the permanent occlusion model was smaller than the maximum value in the thrombotic occlusion model (12.5 vs. 17.4%; P < 0.05, n = 6). CFRs may constitute an important factor contributing to the extent of cerebral infarction.
Perinatal ANG II programs adult blood pressure, glomerular number, and renal function in rats
Authors: Woods Lori L. , Rasch Ruth
Published: December 2017

ANG II is known to be important in normal renal development, but the long-term consequences of a suppressed renin-angiotensin system (RAS) during the developmental period are not completely understood. This study tested the hypothesis that the RAS in the developing animal is important in long-term regulation of renal function and arterial pressure. Newborn Sprague-Dawley rat pups were given the ANG II AT1receptor antagonist losartan (25 mg ⋅ kg−1⋅ day−1sc) for the first 12 days of postnatal life (Los). Body weights at weaning (22 days) were significantly reduced in Los (53.4 ± 3.2 vs. 64.5 ± 3.6 g in controls); however, at the time of study (∼22 wk), body weights and the kidney-to-body weight ratios were not different. In chronically instrumented conscious animals, glomerular filtration rate and effective renal plasma flow were reduced by 27 and 20%, respectively, in Los; the filtration fraction was not different. Maximal urine concentrating ability was also reduced in Los (1,351 ± 45 vs. 2,393 ± 52 mosmol/kg in controls). Mean arterial pressure was significantly higher in Los (134 ± 3 vs. 120 ± 1 mmHg). The number of glomeruli per kidney was reduced by 42% in Los, but the total glomerular volume was unchanged. Thus perinatal blockade of ANG II AT1receptors results in fewer but enlarged glomeruli, reduced renal function, and an increased arterial pressure in adulthood. These data indicate that perinatal ANG II, acting via AT1receptors, plays an important role in renal development and long-term control of renal function and arterial pressure. Physiological conditions that cause suppression of the RAS in the developing animal may have long-term consequences for renal function and blood pressure.
Effects of homologous atrial natriuretic peptide on drinking and plasma ANG II level in eels
Authors: Tsuchida Takamasa , Takei Yoshio
Published: December 2017

The effects of eel atrial natriuretic peptide (ANP) on drinking were investigated in eels adapted to freshwater (FW) or seawater (SW) or in FW eels whose drinking was stimulated by a 2-ml hemorrhage. An intra-arterial infusion of ANP (0.3–3.0 pmol ⋅ kg−1⋅ min−1), which increased plasma ANP level 1.5- to 20-fold, inhibited drinking dose dependently in all groups of eels. The drinking rate recovered to the level before ANP infusion within 2 h after infusate was replaced by saline. The inhibition at 3.0 pmol ⋅ kg−1⋅ min−1was profound in FW eels and hemorrhaged FW eels, whereas significant drinking still remained after inhibition in SW eels. Plasma ANG II concentration also decreased dose dependently during ANP infusion and recovered to the initial level after saline infusion in all groups of eels. The decrease at 3.0 pmol ⋅ kg−1⋅ min−1was large in FW eels and hemorrhaged FW eels compared with that of SW eels. Thus the changes in drinking rate and plasma ANG II level were parallel during ANP infusion. Plasma sodium concentration and osmolality decreased during ANP infusion in SW and FW eels, and they were restored after saline infusion. In hemorrhaged FW eels, however, ANP infusion did not alter plasma sodium concentration and osmolality. Hematocrit did not change during ANP infusion in any group of eels. Collectively, ANP infusion at physiological doses decreased drinking rate and plasma ANG II concentration in parallel in both FW and SW eels. It remains undetermined whether the inhibition of drinking is caused by direct action of ANP or through inhibition of ANG II, which is known as a potent dipsogen in all vertebrate species, including eels.
Evidence that brain angiotensin II is involved in both thirst and sodium appetite in baboons
Authors: Blair-West J. R. , Carey K. D. , Denton D. A. , Weisinger R. S. , Shade R. E.
Published: December 2017

The roles of ANG II in the brain mechanisms subserving thirst and Na appetite in baboons were investigated by chronic intracerebroventricular infusions of ANG II and AT1-receptor antagonists using subcutaneous miniosmotic pumps and by oral administration of captopril. ANG II at 3 or 5 μg/h for 7 days increased water intake from 2,455 ± 107 to 7,052 ± 562 ml/day by day 6 and 300 mM NaCl intake from 8.3 ± 1.1 to 275 ± 87 mmol/day by day 5. Concurrent intracerebroventricular losartan (300 μg/h) did not substantially reduce these responses, but they were abolished by intracerebroventricular ZD-7155 (50 μg/h). The increase of 300 mM NaCl intake when it was offered after intramuscular injection of furosemide, 2 mg ⋅ kg−1 ⋅ day−1for 3 days, was unaltered by intracerebroventricular losartan (300 μg/h) but was reduced by intracerebroventricular ZD-7155 (50 μg/h) infused throughout Na depletion/repletion; oral captopril (1 g, 3 and 18 h before access to 300 mM NaCl) also reduced NaCl intake. Restriction of water intake to 25% of daily intake for 3 days caused a high intake of water on day 4, and this was reduced by intracerebroventricular losartan (300 μg/h) infused throughout the period of water restriction/rehydration. These novel results in a primate species suggest that brain ANG II is involved in both thirst and Na appetite, acting via AT1 receptors.
Apparent thermogenic effect of injected glucagon is not due to a direct effect on brown fat cells
Authors: Dicker Andrea , Zhao Jin , Cannon Barbara , Nedergaard Jan
Published: December 2017

To examine the significance of brown adipose tissue for the thermogenic response to glucagon, we injected glucagon intraperitoneally into rats (that have glucagon-sensitive brown fat cells) and into hamsters (that have glucagon-insensitive brown fat cells). Although a thermogenic response to glucagon injection was apparently observed in rats, this response was not augmented by cold acclimation and was not dose dependent. Similar observations were made in hamsters. The thermogenic response could be fully blocked by prior injection of the β-adrenergic blocker propranolol. Thus no direct thermogenic response to injected glucagon could be demonstrated, and the thermogenic response observed was fully due to vehicle injection. However, glucagon injection was able to unmask mitochondrial [3H]GDP binding. As expected, isolated brown fat cells from rats and mice responded thermogenically to glucagon but brown fat cells from hamsters were unresponsive. The EC50of the rat brown fat cells was high (5 nM); these cells also responded to secretin, with an EC50of 22 nM. It was concluded that, in contrast to earlier observations, no thermogenic response to injected glucagon could be observed; this may be related to differences in glucagon preparations. Brown fat cells from certain species are, however, glucagon sensitive. It is uncertain whether glucagon is the endogenous agonist for these receptors, but the presence of the glucagon-responsive receptor indicates alternative means to norepinephrine for stimulation of brown adipose tissue thermogenesis and, probably, of recruitment.
Plasma hyperosmolality and arterial pressure regulation during heating in dehydrated and awake rats
Authors: Nakajima Yasufumi , Nose Hiroshi , Takamata Akira
Published: December 2017

To gain better insights into the effect of dehydration on thermal and cardiovascular regulation during hyperthermia, we examined these regulatory responses during body heating in rats under isosmotic hypovolemia and hyperosmotic hypovolemia. Rats were divided into four groups: normovolemic and isosmotic (C), hypovolemic and isosmotic [L, plasma volume loss (ΔPV) = −20% of control], hypovolemic and less hyperosmotic [HL1, increase in plasma osmolality (ΔPosm) = 23 mosmol/kgH2O, ΔPV = −16%], and hypovolemic and more hyperosmotic (HL2, ΔPosm = 52 mosmol/kgH2O, ΔPV = −17%). Hyperosmolality was attained by subcutaneous injection of hypertonic saline and hypovolemia by intra-arterial injection of furosemide before heating. Then rats were placed in a thermocontrolled box (35°C air temperature, ∼20% relative humidity) for 1–2 h until rectal temperatures (Tre) reached 40.0°C. Mean arterial pressure in L decreased with rise in Tre( P < 0.001), whereas mean arterial pressure remained constant in the other groups. Maximal tail skin blood flow in L, HL1, and HL2 was decreased to ∼30% of that in C ( P < 0.001). Tre threshold for tail skin vasodilation (TVD) was not changed in L, whereas the threshold shifted higher in the HL groups. Trethreshold for TVD was highly correlated with Posm( r = 0.94, P < 0.001). Heart rate in the HL groups increased with rise in Tre( P < 0.001), whereas it remained unchanged in C and L. Cardiovascular responses to heating were not influenced by V1 antagonist in C, L, and HL2. Thus isotonic hypovolemia attenuates maximal tail skin blood flow, whereas hypertonic hypovolemia causes an upward shift of Tre threshold for TVD and an increase in heart rate during hyperthermia. These results suggest that plasma hyperosmolality stimulates pressor responses in the hypovolemic condition that subsequently contribute to arterial pressure regulation during heat stress.
Effects of meal volume and posture on gastric emptying of solids and appetite
Authors: Doran Selena , Jones Karen L. , Andrews Jane M. , Horowitz Michael
Published: December 2017

The effects of volume and posture on gastric emptying and intragastric distribution of a solid meal and appetite were evaluated. Eight normal volunteers were studied on four occasions, on each of which a meal comprising ground beef mixed with tomato sauce of either 650 g (“large”) or 217 g (“small”) was eaten. Two studies were performed while the subject was lying in the left lateral decubitus position, and two studies were performed while the subject was sitting so that in each subject data were available for both meals and in both postures. Hunger and fullness were evaluated using a visual analog questionnaire. In both postures and after both meals, gastric emptying approximated a linear pattern after an initial lag phase. The lag phase was shorter for the large meal when compared with the small meal [sitting: large 13 ± 5 vs. small 29 ± 7 min; left lateral: large 16 ± 3 vs. small 24 ± 3 min, F(1,7) = 46.3, P < 0.0005]. In both postures the contents of the total [ F(1,7) = 1794.5, P < 0.0001], proximal [ F(1,7) = 203.7, P < 0.0001], and distal [ F(1,7) = 231.5, P < 0.0001] stomach were greater after the large meal when compared with the small meal. Although the 50% emptying time was greater with the large than the small meal [ F(1,7) = 40.8, P < 0.001], the postlag emptying rate (g/min) was more rapid with the large meal [sitting: large 1.7 ± 0.2 vs. small 1.1 ± 0.1 g/min; left lateral: large 1.8 ± 0.1 vs. small 1.3 ± 0.04 g/min, F(1,7) = 44.7, P < 0.0005]. There was a significant interaction between meal volume and posture for retention in the distal stomach [ F(1,7) = 7.14, P < 0.05]. Contrasts were used to evaluate the effects of volume and posture between the four studies and demonstrated an effect of posture for the large [ F(1,21) = 18.7, P < 0.005] but not the small [ F(1,21) = 0.30, P = 0.60] meal so that the retention was greater in the sitting when compared with the left lateral position. The magnitude of the postprandial increase in fullness [ F(1,7) = 7.8, P < 0.05] and reduction in hunger [ F(1,7) = 5.9, P < 0.05] was greater with the large meal. We conclude that meal volume has a major effect on gastric emptying; in contrast posture has only a minor impact on intragastric meal distribution, which is observed only after a large meal, and no effect on gastric emptying.
Arterial baroreceptors control blood pressure and vasopressin responses to hemorrhage in conscious dogs
Authors: Thrasher Terry N. , Keil Lanny C.
Published: December 2017

The goal of this study was to determine the role of arterial baroreceptors in the reflex control of arginine vasopressin (AVP), renin, and cortisol secretion in response to a 30-ml/kg hemorrhage in conscious dogs. The hormonal responses were measured in six dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD + CD. In the intact condition, mean arterial pressure (MAP) was maintained at control levels until blood loss reached 20 ml/kg and the absolute magnitude of the fall at 30 ml/kg was 35 ± 10 mmHg. Similar responses were obtained during acute CD. In contrast, MAP fell earlier (at 5 ml/kg, P < 0.05) and to much lower levels in both the SAD and SAD + CD conditions. The individual slopes relating systolic pressure to plasma AVP, renin activity (PRA), and cortisol were used to compare the treatment effects using a 2 × 2 factorial analysis. There was a significant ( P < 0.01) effect of SAD on the slope relating AVP to systolic pressure but no effect of CD and no SAD × CD interaction. In contrast, there was no effect of either SAD or CD on the relationship between PRA or plasma cortisol and systolic pressure. These results indicate that maintenance of blood pressure and the normal pattern of AVP secretion during hemorrhage depend on intact arterial baroreceptor reflexes.
Central α2-receptor mechanisms contribute to enhanced renal responses during ketamine-xylazine anesthesia
Authors: Cabral Antonio De Melo , Kapusta Daniel R. , Kenigs Velga A. , Varner Kurt J.
Published: December 2017

We have recently developed an experimental approach to study central opioid control of renal function in anesthetized rats. This model system uses the intravenous infusion of the α2-agonist xylazine to enhance basal levels of urine flow rate and urinary sodium excretion in ketamine-anesthetized rats. This study examined the contribution of central and peripheral α2-adrenergic receptor mechanisms in mediating the enhanced renal excretory responses produced by xylazine. In ketamine-anesthetized rats, the enhanced levels of urine flow rate and urinary sodium excretion produced by the intravenous infusion of xylazine were reversed by the intravenous bolus injection of the α2-adrenoceptor antagonist yohimbine but not by the α1-adrenoceptor antagonist terazosin. In separate animals the intracerebroventricular administration of yohimbine only reduced urine flow rate by ∼50% but did not alter urinary sodium excretion. The decrease in urine flow rate produced by intracerebroventricular yohimbine was reversed by the intravenous injection of a selective V2-vasopressin receptor antagonist. In a separate group of ketamine- and xylazine-anesthetized rats, the bilateral microinjection of yohimbine into the hypothalamic paraventricular nucleus (PVN) also significantly decreased urine flow rate by 54% without altering urinary sodium excretion. The microinjection of the β-adrenoceptor antagonist propranolol into the PVN did not alter either renal excretory parameter. These results suggest that during intravenous infusion, xylazine increases urine flow rate by activating α2-adrenergic receptors in the PVN, which in turn decrease vasopressin release. The ability of α-adrenergic mechanisms in the PVN to selectively influence the renal handling of water, but not sodium, may contribute to the reported dissociation of the natriuretic and diuretic responses of α2-adrenoceptor agonists.
Pregnancy-induced changes in central response to atrial distension mimicked by progesterone metabolite
Authors: Deng Yiming , Kaufman Susan
Published: December 2017

In virgin female rats, atrial distension (an index of blood volume expansion) causes an increase in c- fos expression in the paraventricular nucleus of the lateral hypothalamus. During pregnancy, this response is markedly attenuated. We tested the effects of 3α-hydroxy-5α-pregnan-20-one (3α-OH-DHP) on activation of central pathways following stimulation of the atrial volume receptors. Not only does this progesterone metabolite increase during pregnancy, but it has already been implicated in pregnancy-induced changes in the baroreflex. Female rats were prepared with indwelling venous cannulas and intracardiac balloons that, when inflated, caused a discrete localized stimulation of the atrial volume receptors in the absence of changes in cardiac hemodynamics. Seven days later, the rats were infused with 3α-OH-DHP dissolved in cyclodextrin and the intracardiac balloons were inflated. One hour later, the rats were killed and fixed by perfusion and the brains were prepared for visualization of c- fos activity. Infusion with 3α-OH-DHP significantly reduced the central response to atrial distension, i.e., it mimicked pregnancy. These results are consistent with the suggestion that this metabolite of progesterone may be an important factor in cardiovascular adaptation to pregnancy.
Accommodation dynamics in aging rhesus monkeys
Authors: Croft Mary Ann , Kaufman Paul L. , Crawford Kathryn S. , Neider Michael W. , Glasser Adrian , Bito Laszlo Z.
Published: December 2017

Accommodation, the mechanism by which the eye focuses on near objects, is lost with increasing age in humans and monkeys. This pathophysiology, called presbyopia, is poorly understood. We studied aging-related changes in the dynamics of accommodation in rhesus monkeys aged 4–24 yr after total iridectomy and midbrain implantation of an electrode to permit visualization and stimulation, respectively, of the eye’s accommodative apparatus. Real-time video techniques were used to capture and quantify images of the ciliary body and lens. During accommodation in youth, ciliary body movement was biphasic, lens movement was monophasic, and both slowed as the structures approached their new steady-state positions. Disaccommodation occurred more rapidly for both ciliary body and lens, but with longer latent period, and slowed near the end point. With increasing age, the amplitude of lens and ciliary body movement during accommodation declined, as did their velocities. The latent period of lens and ciliary body movements increased, and ciliary body movement became monophasic. The latent period of lens and ciliary body movement during disaccommodation was not significantly correlated with age, but their velocity declined significantly. The age-dependent decline in amplitude and velocity of ciliary body movements during accommodation suggests that ciliary body dysfunction plays a role in presbyopia. The age changes in lens movement could be a consequence of increasing inelasticity or hardening of the lens, or of age changes in ciliary body motility.
Gender differences in autonomic functions associated with blood pressure regulation
Authors: Convertino Victor A.
Published: December 2017

Functions of carotid and aortic baroreflex control of heart rate (HR), cardiopulmonary baroreflex control of vascular resistance, adrenoreceptor responsiveness, indexes of baseline vagal and sympathetic tone, circulating blood volume, and venous compliance were compared in men and women to test the hypothesis that lower orthostatic tolerance in women would be associated with lower responsiveness of specific mechanisms of blood pressure regulation. HR, stroke volume (SV), cardiac output (Q˙), mean arterial blood pressure (MAP), central venous pressure, forearm (FVR) and leg (LVR) vascular resistance, catecholamines, and changes in leg volume (%ΔLV) were measured during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 7 females and 10 males matched for age and fitness. LBNP tolerance for the women (797 ± 63 mmHg/min) was 35% lower ( P = 0.002) than 1,235 ± 101 mmHg/min for the men. At presyncope, SV,Q˙, MAP, and %ΔLV were lower ( P < 0.05) in females compared with males, whereas HR, FVR, and total peripheral resistance were similar in both groups. Lower LBNP tolerance in females was associated with reduced HR response to carotid baroreceptor stimulation, lower baseline cardiac vagal activity, greater decline inQ˙ induced by LBNP, increased β1-adrenoreceptor responsiveness, greater vasoconstriction under equal LBNP, lower levels of circulating NE at presyncope, and lower relative blood volume. The results of this investigation support the hypothesis that women have less responsiveness in mechanisms that underlie blood pressure regulation under orthostatic challenge.
Effect of repeated stress on body weight and body composition of rats fed low- and high-fat diets
Authors: Harris Ruth B. S. , Zhou Jun , Youngblood Bradley D. , Rybkin Igor I. , Smagin Gennady N. , Ryan Donna H.
Published: December 2017

Exposure to the moderate stressor of 3-h restraint for 3 consecutive days causes a temporary drop in food intake but a permanent reduction in body weight in adult rats. Young rats did not show the same response. Food intake of adult rats exposed to repeated restraint was significantly lower than that of controls for 4 days after the end of stress, and there was no rebound hyperphagia. Body weight remained significantly lower for at least 40 days after stress. When the rats were fed a high-fat diet of 80% chow and 20% vegetable shortening (48% kcal fat, 16% protein), lean body mass accounted for all of the weight loss in stressed rats. When the experiment was repeated with a purified high-fat diet containing corn oil and coconut oil as the source of fat (41% kcal fat, 16% protein), weight loss consisted of both lean and fat tissue. There were no sustained changes in single time point measures of corticosterone, insulin, or leptin that could account for the reduced body weight in these rats.
Crucial role of milk-borne insulin in the development of pancreatic amylase at the onset of weaning in rats
Authors: Kinouchi Toshi , Koizumi Kyoko , Kuwata Tamotsu , Yajima Takaji
Published: December 2017

The development of pancreatic amylase activity was examined in rats fed in regular cages or in special cages, designed so the pups could not reach solid food to prevent weaning. In both groups, the amylase activity in zymogen granules increased in rat pups aged 14 days, peaked at 18 days, and thereafter remained at a 1.6-fold higher level than at 14 days of age. An increase in the plasma concentration of immunoreactive insulin preceded the increase of amylase activity, whereas the plasma concentration of C-peptide, indicating the secretion rate of endogenous insulin, remained unchanged. The administration of insulin at 20 ng/ml (the physiological concentration) in the milk formula caused an increase in the plasma insulin concentration of 17-day-old pups. In addition, increased pancreatic amylase activity was observed in 17-day-old rats raised on milk formula to which insulin was added. We propose that the increase of amylase activity at the beginning of weaning is dependent on the milk-borne insulin and not on the dietary change in rats.
Sepsis in mice stimulates muscle proteolysis in the absence of IL-6
Authors: Williams Arthur , Wang Jing Jing , Wang Li , Sun Xiaoyan , Fischer Josef E. , Hasselgren Per-Olof
Published: December 2017

We tested the role of interleukin-6 (IL-6) in sepsis-induced muscle proteolysis by determining ubiquitin mRNA levels and protein breakdown rates in incubated extensor digitorum longus muscles from septic and sham-operated IL-6 knockout and wild-type mice. In addition, the effect of treatment of mice with human recombinant IL-6 on muscle protein breakdown rates was determined. Finally, protein breakdown rates were measured in myotubes treated for up to 48 h with different concentrations of IL-6. Sepsis in wild-type mice resulted in an approximately ninefold increase in plasma IL-6 levels, whereas IL-6 was not detectable in plasma of sham-operated or septic IL-6 knockout mice. Total and myofibrillar muscle protein breakdown rates were increased by ∼30% and threefold, respectively, in septic IL-6 wild-type mice with an almost identical response noted in septic IL-6 knockout mice. Ubiquitin mRNA levels determined by dot blot analysis were increased during sepsis in muscles from both IL-6 knockout and wild-type mice, although the increase was less pronounced in IL-6 knockout than in wild-type mice. Treatment of normal mice or of cultured L6 myotubes with IL-6 did not influence protein breakdown rates. The present results suggest that IL-6 does not regulate muscle proteolysis during sepsis.
Photoperiodic responses of four wild-trapped desert rodent species
Authors: El-Bakry Hanan A. , Zahran Wafaa M. , Bartness Timothy J.
Published: December 2017

The purpose of this study was to examine the effect of the photoperiod on reproductive status and body and lipid masses in four Egyptian desert rodent species ( Dipodillus dasyurus, Acomys cahirinus, Gerbillus andersoni, and Gerbillus pyramidum). Adult males and females were housed in long days for 11 wk. At that time, one-half of the animals were killed and the remaining animals were moved to short days (SDs) for 11 wk. Some individuals of Gerbillus andersoni and Gerbillus pyramidum had access to running wheels. Testes index and spermatogenesis, but not testis mass, were decreased in all species in SDs. In contrast, SDs did not affect female reproductive status in all species. Exercise stimulated spermatogenesis but did not affect female reproductive status. SDs increased body and lipid masses in male Acomys cahirinus, but not in other species. Collectively, these desert rodent species were responsive to day length changes, but these changes alone did not induce robust alterations in reproductive status and body and lipid masses.
c-Fos induction in spinal cord neurons after renal arterial or venous occlusion
Authors: Rosas-Arellano M. Patricia , Solano-Flores L. Pastor , Ciriello John
Published: December 2017

Experiments were done in the anesthetized rat to identify the dorsal root ganglia (DRG) and the spinal cord segments that contain neurons activated by either renal venous occlusion (RVO) or by renal arterial occlusion (RAO). Fos induction, detected immunohistochemically in DRG and the spinal cord neurons, was used as a marker for neuronal activation. RVO induced Fos immunoreactivity in neurons in the DRG of spinal segments T8-L2on the side ipsilateral to that of occlusion. The largest number of Fos-labeled neurons was found in the T11 DRG. In the spinal cord the largest number of Fos-labeled neurons was found in the ipsilateral dorsal horn of spinal segments T11-T12, predominantly in a cluster near the dorsomedial edge of laminae I-II. A few additional Fos-labeled neurons were observed in laminae IV and V. After RAO Fos-labeled neurons were found in the ipsilateral DRG of spinal segments similar to those observed to contain neurons after RVO. However, most of the Fos-labeled neurons were observed within the T12-L1DRG. In the spinal cord Fos-labeled neurons were scattered throughout lamina I-II of the ipsilateral dorsal horn of spinal segments T8-L2, although the largest number was observed at the T13 level. Additionally, a distinct cluster of Fos-labeled neurons was observed predominantly in the region of the ipsilateral intermediolateral cell column, although a few neurons were found scattered throughout the nucleus intercalatus, central autonomic areas, and laminae IV and V of the cord bilaterally. No Fos labeling was observed in the complementary contralateral DRG or dorsal horns after either RVO or RAO. In addition, renal nerve transection prevented Fos labeling in the ipsilateral DRG and dorsal horns after RVO or RAO. Taken together, these data suggest that functionally different renal afferent fibers activate DRG neurons that may have distinct projections in the spinal cord.
Circadian rhythms and depression: effects of exercise in an animal model
Authors: Solberg Leah C. , Horton Teresa H. , Turek Fred W.
Published: December 2017

There is a clear link between altered circadian rhythms and depressive disorders, although the nature of this relationship is unknown. In addition, exercise affects both mood and alters clock function. To investigate the relationship between circadian rhythms, depression, and exercise, 3-wk-old mice housed on a 12:12-h light-dark cycle were exposed to chronic stress (CS) for 6 wk before being placed into constant darkness (DD). One-half of both the control and stressed mice were given access to a running wheel. Stressed mice consumed significantly less of a 2% sucrose solution during CS and exhibited a significant increase in immobility in the forced swim test 3 wk after the termination of stress relative to control mice. These effects were more pronounced in mice without running wheels. Stressed mice also exhibited altered percent distribution of total activity and increased fragmentation of daily activity rhythms during CS relative to control mice. Alterations in percent distribution were more pronounced in animals without running wheels. No activity rhythm changes were seen in DD, and there were no differences in light-induced phase shifts between stressed and control mice. These results suggest that CS causes long-term depressive-like symptoms but does not have long-lasting effects on activity rhythms. These changes were more pronounced in mice without running wheels, suggesting that exercise may protect against the harmful effects of stress.
Ovarian steroid regulation of angiotensin II-induced water intake in the rat
Authors: Kisley Lori R. , Sakai Randall R. , Ma Li Yun , Fluharty Steven J.
Published: December 2017

Spontaneous water intake as well as thirst elicited by ANG II has been shown to be influenced by the stage of the estrous cycle in the female rat. In these experiments, the contribution of each of the ovarian steroid hormones to the regulation of water intake was examined. Ovariectomized female rats were given replacement doses of estrogen, progesterone, or both, and their responsiveness to an intracerebroventricular injection of ANG II was tested. Forty-eight-hour treatment with estradiol benzoate attenuated ANG II-induced thirst by as much as 70% compared with control animals. The effect of estrogen on drinking was dose dependent and could be completely blocked with concurrent administration of the antiestrogen CI-628. In contrast, progesterone, given alone or after estrogen, did not significantly affect ANG II-induced water intake when animals were tested at 4 or 24 h after steroid administration. A central interaction between the peptide hormone ANG II and estrogen, involving a genomic mechanism, may underlie the cyclicity in water intake behavior observed in the rat.
Upregulation of M-creatine kinase and glyceraldehyde3-phosphate dehydrogenase: two markers of muscle disuse
Authors: Cros Nathalie , Muller Jacky , Bouju Sophie , Piétu Geneviève , Jacquet Chantal , Léger Jean J. , Marini Jean-François , Dechesne Claude A.
Published: December 2017

Muscle disuse induces substantial alterations in the highly plastic skeletal muscle tissues, which occur especially in antigravity slow muscles. We differentially screened a muscle cDNA array to identify modifications in gene profile expression induced in slow rat soleus muscle mechanically unloaded by hindlimb suspension as a model for muscle disuse. This study focused on muscle creatine kinase mRNA and protein and glyceraldehyde-3-phosphate dehydrogenase mRNA, which were found to be upregulated in unweighted muscles. These upregulations were analyzed over a 4-wk time course of hindlimb suspension and compared with variations in myosin heavy chain (MHC) isoforms while specifically focusing on type IIx MHC mRNA and protein. The two metabolic marker upregulations clearly preceded IIx MHC contractile protein upregulation. Muscle creatine kinase upregulation was shown to be an excellent, and the earliest, marker of muscle disuse at mRNA and protein levels.
Excitation-induced Ca2+uptake in rat skeletal muscle
Authors: Gissel H. , Clausen T.
Published: December 2017

In isolated rat extensor digitorum longus (EDL) muscle mounted for isometric contractions, chronic low-frequency electrical stimulation was found to lead to an increased uptake of45Ca (154% above control after 240 min) and a progressive accumulation of Ca2+(85% above control after 240 min). In soleus, however, this treatment led to a small, but significant, increase in45Ca uptake (30% above control after 180 min) but no significant accumulation of Ca2+. In muscles mounted for isotonic contractions without any external load, electrical stimulation gave rise to a larger45Ca uptake and accumulation of Ca2+in both EDL and soleus. These uptakes of Ca2+coincided with an accumulation of Na+. During isometric or isotonic contractions, stimulation at 40 Hz increased the initial (60 s) rate of45Ca uptake in soleus muscle 15- and 30-fold, respectively. The stimulation-induced increase in45Ca uptake was only reduced by 17% by the Ca2+-channel blockers nifedipine and verapamil but was blocked by tetrodotoxin. The initial rate of stimulation-induced22Na and45Ca uptake was correlated ( r = 0.80; P < 0.003). Stimulation of Na+channels with veratridine increased45Ca uptake by 93 and 139% in soleus and EDL, respectively ( P < 0.001), effects that were abolished by tetrodotoxin. The results indicate that in skeletal muscle, excitation induces a considerable influx of Ca2+, mediated by Na+channels.
Altered fetal cardiovascular responses to prolonged hypoxia after sinoaortic denervation
Authors: Stein P. , White S. E. , Homan J. , Hanson M. A. , Bocking A. D.
Published: December 2017

This study examines the role of the peripheral chemoreceptors in mediating fetal cardiovascular responses to prolonged hypoxia secondary to reduced uterine blood flow (RUBF). Fetal sheep were chronically instrumented for continuous heart rate (FHR), blood pressure (FBP), and carotid blood flow (CBF) measurements after bilateral sectioning of the carotid sinus and vagus nerves (denervated, n = 7) or sham denervation (intact, n = 7). Four days postoperatively, uterine blood flow was mechanically restricted, reducing fetal arterial oxygen saturation by 47.3% ( P < 0.01). An initial bradycardia was observed in intact (184.0 ± 10.7 to 160.5 ± 10.7 beats/min, not significant) but not denervated fetuses, followed by a tachycardia (180.0 ± 2.2 to 193.7 ± 2.7 beats/min, P < 0.05). FHR increased in denervated fetuses (175.5 ± 8.7 to 203.0 ± 17.9 beats/min, P < 0.05). FBP increased transiently in intact fetuses from 45.1 ± 1.0 to 55.4 ± 3.0 mmHg at 2 h ( P < 0.01), whereas denervated fetuses demonstrated a decrease in FBP from 47.1 ± 4.2 to 37.2 ± 3.7 mmHg (not significant). CBF increased ( P < 0.05) in both intact and denervated fetuses from 39.3 ± 2.8 and 29.7 ± 3.8 ml ⋅ min−1 ⋅ kg−1to 47.7 ± 0.4 and 39.1 ± 0.3 ml ⋅ min−1 ⋅ kg−1, respectively, whereas carotid vascular resistance decreased only in denervated fetuses (1.7 ± 0.1 to 1.1 ± 0.02 mmHg ⋅ ml−1 ⋅ min ⋅ kg−1, P < 0.05). We conclude that the peripheral chemoreceptors play an important role in mediating fetal cardiovascular responses to prolonged RUBF.
Isolation of viable cell types from the gill epithelium of Japanese eelAnguilla japonica
Authors: Wong Chris K. C. , Chan D. K. O.
Published: December 2017

High-purity viable cells with low mitochondria (pavement cells) and mitochondria-rich content (chloride cells) were successfully isolated from the gill epithelium of Japanese eels, using three-step Percoll gradient low-speed centrifugation. Cytochemistry (silver staining for chloride, rhodamine-123, and Mitotracker for mitochondria and actin/spectrin immunofluorescence) and scanning electron microscope images were used to identify the cell types in the gill epithelium of the eel. Pavement cells were isolated at 97 and 98% purity for freshwater- and seawater-adapted eels, respectively, and chloride cells were obtained at 89 and 92% purity. The enzymatic activities of the isolated cells were determined. Na+-K+-ATPase, Mg2+-ATPase, and succinate dehydrogenase were found mainly in the chloride cell. Alkaline Ca2+-ATPase and low- and high-affinity Ca2+-ATPase were about twice as high in the chloride cell compared with the pavement cell. Transfer of eels to seawater resulted in enlargement of chloride cell sizes and significant increases in Na+-K+-ATPase, Mg2+-ATPase, and succinate dehydrogenase activities, while all Ca2+-ATPases declined by ∼60–80%. This is the first report demonstrating the successful isolation of freshwater chloride cells and also an exclusive method of getting high-purity seawater chloride cells. The isolated cells are viable and suitable for further cytological and molecular studies to elucidate the mechanisms of ionic transport.
Effect of behavioral stress on coronary artery relaxation altered with aging in BHR
Authors: Giulumian Ararat D. , Clark Shawn G. , Fuchs Leslie C.
Published: December 2017

Behavioral stress and aging are associated with an increase in vascular disease. This study determined the mechanisms contributing to changes in endothelium-dependent relaxation of isolated coronary arteries (300–350 μm) induced by exposure to 10 days of air-jet stress (2 h/day) in young (3 mo) and old (18 mo) male borderline hypertensive rats (BHR). Aging, alone, did not alter endothelium-dependent relaxation to acetylcholine (ACh) quantitatively but did alter the mechanisms contributing to relaxation to ACh, which was largely dependent on nitric oxide synthase (NOS) in vessels from old, but not young, BHR. Behavioral stress resulted in an enhanced relaxation to ACh that was dependent on NOS in vessels from young stressed compared with young control BHR. Conversely, relaxation to ACh was reduced in coronary arteries from old stressed compared with old control BHR. In vessels from old control BHR, there was an NOS-independent component of relaxation mediated by opening of K+ channels that was absent in vessels from old stressed BHR. The superoxide anion scavenger, tiron, partially restored relaxation, and inhibition of cyclooxygenase largely restored relaxation to ACh in vessels from old stressed BHR. In summary, the effect of behavioral stress was age dependent. ACh-induced relaxation of coronary arteries was enhanced in an NOS-dependent manner in young BHR and was impaired in old BHR due to superoxide anions, vasoconstrictor cyclooxygenase products, and a loss of K+ channel-mediated relaxation.
Arginine vasopressin does not mediate the attenuated febrile response to intravenous IL-1β in pregnant rats
Authors: Eliason Heather L. , Fewell James E.
Published: December 2017

Rats have an attenuated febrile response to intravenous endogenous pyrogen [e.g., interleukin-1β (IL-1β)] near the term of pregnancy. The present experiments were carried out on 25 nonpregnant and 32 pregnant rats to test the hypothesis that arginine vasopressin functioning as an endogenous antipyretic substance in the central nervous system mediates this attenuated febrile response. An intravenous injection of recombinant rat IL-1β (rrIL-1β) after intracerebroventricular vehicle produced a significant increase in core temperature in both nonpregnant and pregnant animals, the magnitude and duration of which was greater in the nonpregnant rats. In nonpregnant rats, intravenous rrIL-1β after intracerebroventricular vasopressin V1-receptor antagonist accentuated the core temperature response compared with that observed with intravenous rrIL-1β after intracerebroventricular vehicle. In pregnant animals, however, intravenous rrIL-1β after intracerebroventricular vasopressin V1-receptor antagonist produced a decrease in core temperature rather than an increase in core temperature, which was observed with intravenous rrIL-1β after intracerebroventricular vehicle. Thus our data do not support the hypothesis that a pregnancy-related activation of arginine vasopressin as an endogenous antipyretic substance in the central nervous system attenuates the febrile response to intravenous rrIL-1β near the term of pregnancy in rats.
Extrinsic inputs to intrinsic neurons in the porcine heart in vitro
Authors: Smith F. M.
Published: December 2017

Convergence of inputs from extrinsic cardiac nerves [vagus and cardiopulmonary (CPN)] on intrinsic cardiac neurons was investigated in the pig ( Sus scrofa). A segment of the right atrial wall containing epicardial neurons along with attached stumps of the right vagus nerve and CPN was maintained in vitro; intracellular recordings were made from 57 neurons. Three types of neuron were identified by their responses to long intracellular depolarizing current pulses: phasic [discharged 1 action potential (AP); 40%]; accommodating (discharged multiple APs decrementing in frequency during pulse; 33%); and tonic (discharged multiple APs at a high frequency; 27%). Sixty-six percent of the neurons responded with excitatory postsynaptic potentials (EPSP) to vagal nerve stimulation; two-thirds of these cells fired APs when EPSP amplitude exceeded threshold level. Postsynaptic responses to vagal nerve stimulation were mediated by nicotinic ion channels; responses were eliminated by hexamethonium. CPN stimulation produced EPSPs but no APs in 17% of the neurons. All neurons responding with postsynaptic depolarizations to CPN stimulation also received vagal inputs. Combined stimulation of the vagus nerve and CPN produced APs in all but one of these neurons. Timolol eliminated postsynaptic responses from CPN stimulation, indicating that these responses involved β-adrenergic receptors and likely resulted from activation of sympathetic postganglionic terminals. These results show that some intrinsic cardiac neurons receive convergent inputs from the CPN and vagus nerve. It is suggested that such neurons represent intraganglionic sites for sympathetic-parasympathetic interactions in neural control of the heart.