bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice
Authors: Swart I. , Jahng J. W. , Overton J. M. , Houpt T. A.
Published: March 2015

Food deprivation (FD) increases hypothalamic neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels and decreases proopiomelanocortin (POMC) mRNA levels; refeeding restores these levels. We determined the time course of changes in hypothalamic NPY, AGRP, and POMC mRNA levels on refeeding after 24 h FD in C57BL mice by in situ hybridization. After 24 h deprivation, mice were refed with either chow or a palatable mash containing no calories or were injected with murine leptin (100 μg) without food. Mice were perfused 2 or 6 h after treatment. Food deprivation increased hypothalamic NPY mRNA (108 ± 6%) and AGRP mRNA (78 ± 7%) and decreased hypothalamic POMC mRNA (−15 ± 1%). Refeeding for 6 h, but not 2 h, was sufficient to reduce (but not restore) NPY mRNA, did not affect AGRP mRNA, and restored POMC mRNA levels to ad libitum control levels. Intake of the noncaloric mash had no effect on mRNA levels, and leptin administration after deprivation (at a dose sufficient to reduce refeeding in FD mice) was not sufficient to affect mRNA levels. These results suggest that gradual postabsorptive events subsequent to refeeding are required for the restoration of peptide mRNA to baseline levels after food deprivation in mice.
Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone, StAR, and PBR
Authors: Raff Hershel , Hong Julie J. , Oaks Martin K. , Widmaier Eric P.
Published: March 2015

The adrenocortical response to hypoxia may be a critical component of the adaptation to this common neonatal stress. Little is known about adrenal function in vivo in hypoxic neonates. The purpose of this study was to evaluate adrenocortical responses to ACTH in suckling rat pups exposed to hypoxia from birth to 5–7 days of age compared with normoxic controls. We also evaluated potential cellular controllers of steroidogenic function in situ. In 7-day-old pups at 0800, hypoxia from birth resulted in increased basal (12.2 ± 1.4 ng/ml; n = 12) and ACTH-stimulated (94.0 ± 9.4 ng/ml; n = 14) corticosterone levels compared with normoxic controls (basal = 8.3 ± 0.5 ng/ml; n = 11; stimulated = 51.3 ± 3.8 ng/ml; n = 8). This augmentation occurred despite no significant difference in plasma ACTH levels in normoxic vs. hypoxic pups before (85 ± 4 vs. 78 ± 8 pg/ml) or after (481 ± 73 vs. 498 ± 52 pg/ml) porcine ACTH injection (20 μg/kg). This effect was similar in the afternoon at 6 days of age and even greater at 5 days of age at 0800. The aldosterone response to ACTH was not augmented by exposure to hypoxia from birth. Adrenocortical hypoxia-inducible factor (HIF)-1α mRNA was undetectable by RT-PCR. Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age. Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth. We conclude that hypoxia from birth results in an augmentation of the corticosterone but not aldosterone response to ACTH. This effect appears to be mediated at least in part by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR) and to occur independently of measurable changes in endogenous plasma ACTH. The augmentation of the corticosterone response to acute increases in ACTH in hypoxic pups is likely to be an important component of the overall physiological adaptation to hypoxia in the neonate.
cAMP and in vivo hypoxia inducetob,ifr1, andfosexpression in erythroid cells of the chick embryo
Authors: Dragon Stefanie , Offenhäuser Nina , Baumann Rosemarie
Published: March 2015

During avian embryonic development, terminal erythroid differentiation occurs in the circulation. Some of the key events, such as the induction of erythroid 2,3-bisphosphoglycerate (2,3-BPG), carbonic anhydrase (CAII), and pyrimidine 5′-nucleotidase (P5N) synthesis are oxygen dependent (Baumann R, Haller EA, Schöning U, and Weber M, Dev Biol 116: 548–551, 1986; Dragon S and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 280: R870–R878, 2001; Dragon S, Carey C, Martin K, and Baumann R, J Exp Biol202: 2787–2795, 1999; Dragon S, Glombitza S, Götz R, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R982–R989, 1996; Dragon S, Hille R, Götz R, and Baumann R, Blood 91: 3052–3058, 1998; Million D, Zillner P, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 261: R1188–R1196, 1991) in an indirect way: hypoxia stimulates the release of norepinephrine (NE)/adenosine into the circulation (Dragon et al., J Exp Biol 202: 2787–2795, 1999; Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982–R989, 1996). This leads via erythroid β-adrenergic/adenosine A2receptor activation to a cAMP signal inducing several proteins in a transcription-dependent manner (Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982–R989, 1996; Dragon et al., Blood 91: 3052–3058, 1998; Glombitza S, Dragon S, Berghammer M, Pannermayr M, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R973–R981, 1996). To understand how the cAMP-dependent processes are initiated, we screened an erythroid cDNA library for cAMP-regulated genes. We detected three genes that were strongly upregulated (>5-fold) by cAMP in definitive and primitive red blood cells. They are homologous to the mammalian Tob, Ifr1, and Fos proteins. In addition, the genes are induced in the intact embryo during short-term hypoxia. Because the genes are regulators of proliferation and differentiation in other cell types, we suggest that cAMP might promote general differentiating processes in erythroid cells, thereby allowing adaptive modulation of the latest steps of erythroid differentiation during developmental hypoxia.
Expression and binding activity of the glucocorticoid receptor are upregulated in septic muscle
Authors: Sun Xiaoyan , Fischer David R. , Pritts Timothy A. , Wray Curtis J. , Hasselgren Per-Olof
Published: March 2015

We examined the influence of sepsis, induced by cecal ligation and puncture in rats, on the protein and gene expression and hormone binding activity of the glucocorticoid receptor (GR) in skeletal muscle. Sepsis resulted in increased GR mRNA and protein levels and upregulated hormone binding activity in extensor digitorum longus and soleus muscles. Scatchard analysis suggested that the increased GR hormone binding activity reflected an increased number of hormone binding sites, whereas receptor affinity for glucocorticoids was unchanged. The GR antagonist RU-38486 blocked the sepsis-induced increase in GR expression and hormone binding activity, implicating a positive regulatory effect of glucocorticoids on GR expression and binding activity under the present experimental conditions. The results suggest that glucocorticoid-dependent metabolic changes in skeletal muscle during sepsis may reflect not only high circulating glucocorticoid levels but increased amounts and hormone binding activity of the GR as well.
Effects of fasting on thermoregulatory processes and the daily oscillations in rats
Authors: Nagashima Kei , Nakai Sadamu , Matsue Kenta , Konishi Masahiro , Tanaka Mutsumi , Kanosue Kazuyuki
Published: March 2015

To investigate the mechanism involved in the reduction of body core temperature (Tcore) during fasting in rats, which is selective in the light phase, we measured Tcore, surface temperature, and oxygen consumption rate in fed control animals and in fasted animals on day 3 of fasting and day 4 of recovery at an ambient temperature (Ta) of 23°C by biotelemetry, infrared thermography, and indirect calorimetry, respectively. On the fasting day, 1) Tcore in the light phase decreased ( P < 0.05) from the control; however, Tcore in the dark phase was unchanged, 2) tail temperature fell from the control ( P < 0.05, from 30.7 ± 0.1 to 23.9 ± 0.1°C in the dark phase and from 29.4 ± 0.1 to 25.2 ± 0.2°C in the light phase), 3) oxygen consumption rate decreased from the control ( P < 0.05, from 24.37 ± 1.06 to 16.24 ± 0.69 ml · min−1 · kg body wt−0.75 in the dark phase and from 18.91 ± 0.64 to 14.00 ± 0.41 ml · min−1 · kg body wt−0.75 in the light phase). All these values returned to the control levels on the recovery day. The results suggest that, in the fasting condition, Tcore in the dark phase was maintained by suppression of the heat loss mechanism, despite the reduction of metabolic heat production. In contrast, the response was weakened in the light phase, decreasing Tcore greatly. Moreover, the change in the regulation of tail blood flow was a likely mechanism to suppress heat loss.
Intraventricular insulin potentiates the anorexic effect of corticotropin releasing hormone in rats
Authors: Richardson Ralph D. , Omachi Koichi , Kermani Rasoul , Woods Stephen C.
Published: March 2015

Intraventricular corticotropin releasing hormone (CRH) suppresses food intake and body weight as a stress response. Insulin, acting within the brain, also suppresses food intake and body weight, and this suppression is related to caloric homeostasis. We determined if increased insulin within the brain potentiates the anorexic effects of intraventricular CRH. Rats were food deprived for 17 h each day and then given 30-min access to Ensure. One-half received continuous third ventricular infusion of synthetic cerebrospinal fluid via osmotic minipumps, and one-half received insulin (0.6 mU/day). During the infusion, rats also received 0, 0.1, 1.0, or 5.0 μg of CRH into the lateral ventricle just before access to Ensure. Insulin alone had no effect on Ensure intake or body weight. CRH dose dependently reduced Ensure intake in both groups, and the reduction was greater in the insulin group. Hence, central insulin potentiated the ability of centrally administered CRH to suppress food intake. These findings suggest that stress-related influences over food intake, particularly those mediated via CRH, interact with relative adiposity as signaled to the brain by central insulin.
Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid ω-hydroxylase activity
Authors: Xu Fengyun , Straub Wesley O. , Pak Winnie , Su Ping , Maier Kristopher G. , Yu Ming , Roman Richard J. , Ortiz De Montellano Paul R. , Kroetz Deanna L.
Published: March 2015

The cytochrome P-450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that is implicated in the regulation of blood pressure. The identification of selective inhibitors of renal 20-HETE formation for use in vivo would facilitate studies to determine the systemic effects of this eicosanoid. We characterized the acetylenic fatty acid sodium 10-undecynyl sulfate (10-SUYS) as a potent and selective mechanism-based inhibitor of renal 20-HETE formation. A single dose of 10-SUYS caused an acute reduction in mean arterial blood pressure in 8-wk-old spontaneously hypertensive rats. The decrease in mean arterial pressure was maximal 6 h after 10-SUYS treatment (17.9 ± 3.2 mmHg; P < 0.05), and blood pressure returned to baseline levels within 24 h after treatment. Treatment with 10-SUYS was associated with a decrease in urinary 20-HETE formation in vivo and attenuation of the vasoconstrictor response of renal interlobar arteries to ANG II in vitro. These results provide further evidence that 20-HETE plays an important role in the regulation of blood pressure in the spontaneously hypertensive rat.
Inhibition of cyclooxygenase-2: effects on renin secretion and expression in fetal lambs
Authors: Mertz Heather L. , Liu Jingfang , Valego Nancy K. , Stallings Shawn P. , Figueroa Jorge P. , Rose James C.
Published: March 2015

The importance of prostaglandins in the regulation of the renin-angiotensin system during development is not known. These experiments were conducted to examine the effects of prostaglandin synthesis inhibitors on basal and isoproterenol-induced plasma renin concentration and renin gene expression in the late-gestation fetal lamb. Eighteen lamb fetuses ranging in gestational age from 129 to 138 days underwent surgical insertion of femoral arterial and venous catheters under general endotracheal anesthesia. After a period of recovery, animals underwent an infusion of isoproterenol after administration of a saline bolus (control experiments); 24–48 h later a second study was performed after administration of NS-398, a cyclooxygenase (COX)-2 inhibitor, or saline for a second control study. Administration of COX-2 inhibitor significantly reduced baseline plasma renin levels and attenuated responses in fetal renin secretion to isoproterenol infusions. Renal cortical cells from animals receiving COX-2 inhibitor had significantly lower levels of renin mRNA compared with animals receiving only saline. Renal cortical cells in culture from animals receiving only saline exhibited increased levels of renin mRNA when treated with isoproterenol, forskolin, or IBMX. Only forskolin increased renin mRNA levels in renal cortical cells in culture from animals receiving COX-2 inhibitor. We conclude that prostaglandins play a stimulatory role in the regulation of the renin-angiotensin system and are necessary for β-adrenergic stimulation of renin secretion and gene expression in the late-gestation fetal lamb.
Effects of peripheral CCK receptor blockade on feeding responses to duodenal nutrient infusions in rats
Authors: Reidelberger Roger D. , Heimann Dean , Kelsey Linda , Hulce Martin
Published: March 2015

Type A cholecystokinin receptor (CCKAR) antagonists differing in blood-brain barrier permeability were used to test the hypothesis that duodenal delivery of protein, carbohydrate, and fat produces satiety in part by an essential CCK action at CCKARs located peripheral to the blood-brain barrier. Fasted rats with open gastric fistulas received devazepide (1 mg/kg iv) or A-70104 (700 nmol · kg−1· h−1iv) and either a 30-min intravenous infusion of CCK-8 (10 nmol · kg−1· h−1) or duodenal infusion of peptone, maltose, or Intralipid beginning 10 min before 30-min access to 15% sucrose. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of Nα-3-quinolinoyl-d-Glu- N,N-dipentylamide, does not. CCK-8 inhibited sham feeding by ∼50%, and both A-70104 and devazepide abolished this response. Duodenal infusion of each of the macronutrients dose dependently inhibited sham feeding. A-70104 and devazepide attenuated inhibitory responses to each macronutrient. Thus endogenous CCK appears to act in part at CCKARs peripheral to the blood-brain barrier to inhibit food intake.
Fibroblast growth factors as regulators of central nervous system development and function
Authors: Dono Rosanna
Published: March 2015

Fibroblast growth factors (FGFs) are multifunctional signaling proteins that regulate developmental processes and adult physiology. Over the last few years, important progress has been made in understanding the function of FGFs in the embryonic and adult central nervous system. In this review, I will first discuss studies showing that FGF signaling is already required during formation of the neural plate. Next, I will describe how FGF signaling centers control growth and patterning of specific brain structures. Finally, I will focus on the function of FGF signaling in the adult brain and in regulating maintenance and repair of damaged neural tissues.
Developmental changes in cardiac recovery from anoxia-reoxygenation
Authors: Sedmera David , Kucera Pavel , Raddatz Eric
Published: March 2015

The developing cardiovascular system is known to operate normally in a hypoxic environment. However, the functional and ultrastructural recovery of embryonic/fetal hearts subjected to anoxia lasting as long as hypoxia/ischemia performed in adult animal models remains to be investigated. Isolated spontaneously beating hearts from Hamburger-Hamilton developmental stages 14( 14HH), 20HH, 24HH, and 27HH chick embryos were subjected in vitro to 30 or 60 min of anoxia followed by 60 min of reoxygenation. Morphological alterations and apoptosis were assessed histologically and by transmission electron microscopy. Anoxia provoked an initial tachycardia followed by bradycardia leading to complete cardiac arrest, except for in the youngest heart, which kept beating. Complete atrioventricular block appeared after 9.4 ± 1.1, 1.7 ± 0.2, and 1.6 ± 0.3 min at stages 20HH, 24HH, and 27HH, respectively. At reoxygenation, sinoatrial activity resumed first in the form of irregular bursts, and one-to-one atrioventricular conduction resumed after 8, 17, and 35 min at stages 20HH, 24HH, and 27HH, respectively. Ventricular shortening recovered within 30 min except at stage 27HH. After 60 min of anoxia, stage 27HHhearts did not retrieve their baseline activity. Whatever the stage and anoxia duration, nuclear and mitochondrial swelling observed at the end of anoxia were reversible with no apoptosis. Thus the embryonic heart is able to fully recover from anoxia/reoxygenation although its anoxic tolerance declines with age. Changes in cellular homeostatic mechanisms rather than in energy metabolism may account for these developmental variations.
Fos, RVLM-projecting neurons, and spinally projecting neurons in the PVN following hypertonic saline infusion
Authors: Kantzides A. , Badoer E.
Published: March 2015

Hypertonic saline (HTS; 1.7 M) infused intravenously into conscious rats increases the production of Fos, a marker of cell activation, in the hypothalamic paraventricular nucleus (PVN). The parvocellular PVN contains subpopulations of neurons. However, which subpopulations are activated by HTS is unknown. We determined whether PVN neurons that innervate the rostral ventrolateral medulla (RVLM) or the spinal cord (important autonomic sites) expressed Fos following HTS. Experiments were performed 24–96 h after chronic implantation of an intravenous cannula. HTS significantly increased the number of Fos-positive cells. In the parvocellular PVN, the maximum number of Fos-positive cells occurred rostral of the anterior-posterior level at which the number of neurons that projected to the medulla or spinal cord peaked. Compared with controls, HTS did not significantly increase the number of double-labeled neurons. These findings demonstrate that an elevation in plasma osmolality activates PVN neurons but not the subgroups of PVN neurons with projections to the RVLM or to the spinal cord.
Intensity-dependent thermoregulatory responses at the onset of dynamic exercise in mildly heated humans
Authors: Yanagimoto Shuji , Kuwahara Tomoko , Zhang Yuan , Koga Shunsaku , Inoue Yoshimitsu , Kondo Narihiko
Published: March 2015

To investigate quantitatively how sweating and cutaneous blood flow responses at the onset of dynamic exercise are affected by increasing exercise intensity in mildly heated humans, 18 healthy male subjects performed cycle exercise at 30, 50, and 70% of maximal O2 uptake (V̇O2 max) for 60 s in a warm environment. The study was conducted in a climatic chamber with a regulated ambient temperature of 35°C and relative humidity of 50%. The subjects rested in the semisupine position in the chamber for 60 min, and then sweating rate (SR) and skin blood flow were measured during cycle exercise at three different intensities. Changes in the heart rate, rating of perceived exertion, and mean arterial blood pressure were proportional to increasing exercise intensity, whereas esophageal and mean skin temperatures were essentially constant throughout the experiment. The SR on the chest, forearm, and thigh, but not on the palm, increased significantly with increasing exercise intensity ( P < 0.05). The mean SR of the chest, forearm, and thigh increased 0.05 mg·cm-2·min-1 with an increase in exercise intensity equivalent to 10% V̇O2 max. On the other hand, the cutaneous vascular conductance (CVC) on the chest, forearm, and palm decreased significantly with increasing exercise intensity ( P < 0.05). The mean CVC of the chest and forearm decreased 5.5% and the CVC on the palm decreased 8.0% with an increase in exercise intensity equivalent to 10% V̇O2 max. In addition, the reduction in CVC was greater on the palm than on the chest and forearm at all exercise intensities ( P < 0.01). We conclude that nonthermal sweating and cutaneous blood flow responses are exercise intensity dependent but directionally opposite at the onset of dynamic exercise in mildly heated humans. Furthermore, cutaneous blood flow responses to increased exercise intensity are greater in glabrous (palm) than in nonglabrous (chest and forearm) skin.
Urocortin in the lateral septal area modulates feeding induced by orexin A in the lateral hypothalamus
Authors: Wang Chuanfeng , Kotz Catherine M.
Published: March 2015

The intermediate portion of the lateral septum (LSi) contains high levels of urocortin (UCN) peptide and type 2 corticotropin-releasing hormone (CRH) receptor (CRHR2) and has anatomic and functional connections with the lateral hypothalamus (LH). We tested the effect of UCN in the LSi on feeding. Injection of 10 or 30 pmol UCN into LSi significantly decreased feeding in food-deprived rats for 24 h without producing conditioned taste aversion (CTA). Pretreatment with a CRH receptor antagonist, α-helical CRH (α-hCRH), blocked the inhibitory effect of UCN on deprivation-induced feeding at 1 and 2 h postinjection. Furthermore, UCN in the LSi significantly decreased feeding induced by LH-injected orexin A at 2 and 4 h postinjection, and addition of α-hCRH blocked the inhibitory effect of UCN on orexin A-induced feeding. In conclusion, UCN significantly inhibits feeding induced by deprivation and LH-injected orexin A without producing a CTA, an effect that is mediated by CRHR2. These data define the LSi as an important site for UCN-induced anorexia and indicate that LSi UCN may influence orexin A feeding signals in the LH.
Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels
Authors: Prendergast Brian J. , Freeman David A. , Zucker Irving , Nelson Randy J.
Published: March 2015

Golden-mantled ground squirrels ( Spermophilus lateralis) undergo seasonal hibernation during which core body temperature (Tb) values are maintained 1–2°C above ambient temperature. Hibernation is not continuous. Squirrels arouse at ∼7-day intervals, during which Tbincreases to 37°C for ∼16 h; thereafter, they return to hibernation and sustain low Tbs until the next arousal. Over the course of the hibernation season, arousals consume 60–80% of a squirrel's winter energy budget, but their functional significance is unknown and disputed. Host-defense mechanisms appear to be downregulated during the hibernation season and preclude normal immune responses. These experiments assessed immune function during hibernation and subsequent periodic arousals. The acute-phase response to bacterial lipopolysaccharide (LPS) was arrested during hibernation and fully restored on arousal to normothermia. LPS injection (ip) resulted in a 1–1.5°C fever in normothermic animals that was sustained for >8 h. LPS was without effect in hibernating squirrels, neither inducing fever nor provoking arousal, but a fever did develop several days later, when squirrels next aroused from hibernation; the duration of this arousal was increased sixfold above baseline values. Intracerebroventricular infusions of prostaglandin E2provoked arousal from hibernation and induced fever, suggesting that neural signaling pathways that mediate febrile responses are functional during hibernation. Periodic arousals may activate a dormant immune system, which can then combat pathogens that may have been introduced immediately before or during hibernation.
17β-Estradiol decreases hypoxic induction of erythropoietin gene expression
Authors: Mukundan Harshini , Resta Thomas C. , Kanagy Nancy L.
Published: March 2015

Exposure to chronic hypoxia induces erythropoietin (EPO) production to facilitate oxygen delivery to hypoxic tissues. Previous studies from our laboratory found that ovariectomy (OVX) exacerbates the polycythemic response to hypoxia and treatment with 17β-estradiol (E2-β) inhibits this effect. We hypothesized that E2-β decreases EPO gene expression during hypoxia. Because E2-β can induce nitric oxide (NO) production and NO can attenuate EPO synthesis, we further hypothesized that E2-β inhibition of EPO gene expression is mediated by NO. These hypotheses were tested in OVX catheterized rats treated with E2-β (20 μg/day) or vehicle for 14 days and exposed to 8 or 12 h of hypoxia (12% O2) or normoxia. We found that E2-β treatment significantly decreased EPO synthesis and gene expression during hypoxia. E2-β treatment did not induce endothelial NO synthase (eNOS) expression in the kidney but potentiated hypoxia-induced increases in plasma nitrates. We conclude that E2-β decreases hypoxic induction of EPO. However, this effect does not appear to be related to changes in renal eNOS expression.
Intracranial renin alters gustatory neural responses in the nucleus of the solitary tract of rats
Authors: Tamura R. , Norgren R.
Published: March 2015

Activation of the renin-angiotensin system in the brain is considered important in the arousal and expression of sodium appetite. To clarify the effects of directly activating this hormonal cascade, taste neurons in the nucleus of the solitary tract of rats were tested with a battery of sapid stimuli after intracerebroventricular injection of renin or its vehicle. The rats were chronically prepared but lightly anesthetized during the recording procedure. Eighty-five taste neurons were tested: 46 after renin injections and 39 after vehicle. Neural activity was counted for 5.0-s periods without stimulation (spontaneous) and during stimulation with water and sapid chemicals. The averaged responses to each of the standard stimuli (0.1 M NaCl, 0.3 M sucrose, 0.01 M citric acid, and 0.01 M quinine hydrochloride) did not differ significantly between the two conditions. When the rats were tested with a concentration range of NaCl, however, after renin the average responses to the hypertonic 0.3 and 1.0 M stimuli were reduced to 74 and 70%, respectively, compared with those after vehicle injections. A similar tendency was evident for the subsample of neurons that responded best to NaCl, but the effect was smaller. These data are consistent with, but not as dramatic as, those reported after dietary-induced sodium appetite.
Effects of angiotensins on day-night fluctuations and stress-induced changes in blood pressure
Authors: Braga Aline Nardoni Gonçalves , Da Silva Lemos Marisa , Da Silva José Roberto , Fontes Walkíria Ramos Peliky , Augusto Souza Dos Santos Robson
Published: March 2015

In this study we evaluated by telemetry the effects of ANG II and ANG-(1–7) infusion on the circadian rhythms of blood pressure (BP) and heart rate (HR) and on the cardiovascular adjustment resulting from restraint stress in rats. ANG II or ANG-(1–7) or vehicle were infused subcutaneously for 7 days. Restraint stress was carried out before, during, and after infusion at 7-day intervals. Parallel with an increase in MAP, ANG II infusion produced an inversion of MAP circadian rhythm with a significant MAP acrophase inversion. It also produced bradycardia during the first 3 days of infusion. Thereafter, HR progressively increased, reaching values similar to or above those of the control period at the end of the infusion period. HR circadian variation was not changed by ANG II infusion. Strikingly, ANG II significantly attenuated the increase in MAP induced by restraint stress without altering the HR response. ANG-(1–7) infusion produced a slight but significant decrease in MAP restricted to the daytime period. No significant changes in the MAP acrophase were observed. In addition, ANG-(1–7) infusion produced a small but significant sustained bradycardia. ANG-(1–7) did not change cardiovascular responses to restraint stress. These data indicate that ANG II can influence the activity of brain areas involved in the determination of stress-induced or circadian-dependent variations of blood pressure without changing HR fluctuations. A significant modulatory influence of ANG-(1–7) on basal MAP and HR is also suggested.
Vascular responses in vivo to 8-epiPGF2αin normal and hypercholesterolemic pigs
Authors: Krier James D. , Rodriguez-Porcel Martin , Best Patricia J. M. , Romero J. Carlos , Lerman Amir , Lerman Lilach O.
Published: March 2015

Hypercholesterolemia (HC) is characterized by increased circulating 8- epi-prostaglandin-F2α(isoprostane), a vasoconstrictor, marker, and mediator of increased oxidative stress, whose vascular effects might be augmented in HC. Anesthetized pigs were studied in vivo with electron beam computed tomography after a 12-wk normal ( n = 8) or HC ( n = 8) diet. Mean arterial pressure (MAP), single-kidney perfusion, and glomerular filtration rate (GFR) were quantified before and during unilateral intrarenal infusions of U46619 (10 ng · kg−1· min−1) or isoprostane (1 μg · kg−1· min−1). Basal renal perfusion and function were similar, and isoprostane infusion elevated its systemic levels similarly in normal and HC (333 ± 89 vs. 366 ± 48 pg/ml, respectively, P < 0.01 vs. baseline). Both drugs markedly and comparably decreased cortical perfusion and GFR in both groups, whereas medullary perfusion decreased significantly only in HC. Moreover, MAP increased significantly only in HC (+9 ± 3 and +11 ± 3 mmHg, respectively, P≤ 0.05). Hence, in HC, renal functional responses to high-dose isoprostane are largely similar to normal, but the systemic circulation exhibits augmented sensitivity to pathophysiological levels of isoprostane and U46619 , which may potentially play a role in development of hypertension and vascular injury associated with increased oxidative stress.
Cardiovascular alterations and autonomic imbalance in an experimental model of depression
Authors: Grippo Angela J. , Moffitt Julia A. , Johnson Alan Kim
Published: March 2015

Depressed patients with and without a history of cardiovascular pathology display signs, such as elevated heart rate, decreased heart rate variability, and increased physiological reactivity to environmental stressors, which may indicate a predisposition to cardiovascular disease. The specific physiological mechanisms associating depression with such altered cardiovascular parameters are presently unclear. The current study investigated cardiovascular regulation in the chronic mild stress rodent model of depression and examined the specific autonomic nervous system mechanisms underlying the responses. Sprague-Dawley rats exposed to a series of mild, unpredictable stressors over 4 wk displayed anhedonia (an essential feature of human depression), along with elevated resting heart rate, decreased heart rate variability, and exaggerated pressor and heart rate responses to air jet stress. Results obtained from experiments studying autonomic blockade suggest that cardiovascular alterations in the chronic mild stress model are mediated by elevated sympathetic tone to the heart. The present findings have implications for the study of pathophysiological links between affective disorders and cardiovascular disease.
Effects of supine, prone, and lateral positions on cardiovascular and renal variables in humans
Authors: Pump Bettina , Talleruphuus Ulrik , Christensen Niels Juel , Warberg Jørgen , Norsk Peter
Published: March 2015

The hypothesis was tested that changing the direction of the transverse gravitational stress in horizontal humans modulates cardiovascular and renal variables. On different study days, 14 healthy males were placed for 6 h in either the horizontal supine or prone position following 3 h of being supine. Eight of the subjects were in addition investigated in the horizontal left lateral position. Compared with supine, the prone position slightly increased free water clearance (349 ± 38 vs. 447 ± 39 ml/6 h, P = 0.05) and urine output (1,387 ± 55 vs. 1,533 ± 52 ml/6 h, P = 0.06) with no statistically significant effect on renal sodium excretion (69 ± 3 vs. 76 ± 5 mmol/6 h, P = 0.21). Mean arterial pressure and left atrial diameter were similar comparing effects of supine with prone. The prone position induced an increase in heart rate (54 ± 2 to 58 ± 2 beats/min, P < 0.05), total peripheral vascular resistance (13 ± 1 to 16 ± 1 mmHg · min−1 · l−1, P < 0.05), forearm venous plasma concentration of norepinephrine (97 ± 9 to 123 ± 16 pg/ml, P< 0.05), and atrial natriuretic peptide (49 ± 4 to 79 ± 12 pg/ml, P < 0.05), whereas stroke volume decreased (122 ± 5 to 102 ± 3 ml, P < 0.05, n = 6). The left lateral position had no effect on renal variables, whereas left atrial diameter increased (32 ± 1 to 35 ± 1 mm, P < 0.05) and mean arterial pressure decreased (90 ± 2 to mean value of 85 ± 2 mmHg, P < 0.05). In conclusion, the prone position reduced stroke volume and increased sympathetic nervous activity, possibly because of mechanical compression of the thorax with slight impediment of arterial filling. The mechanisms of the slightly augmented urine output in prone position require further experimentation.
Carbon monoxide promotes endothelium-dependent constriction of isolated gracilis muscle arterioles
Authors: Johnson Fruzsina K. , Johnson Robert A.
Published: March 2015

Vascular tissues express heme oxygenase, which metabolizes heme to form carbon monoxide (CO). CO promotes relaxation of vascular smooth muscle but also inhibits nitric oxide (NO) formation. This study examines the hypothesis that CO promotes endothelium- and NO synthase-dependent vasoconstriction of isolated arterioles. Studies were conducted on pressurized first-order gracilis muscle arterioles isolated from anesthetized male Sprague-Dawley rats. Exogenous CO, as well as a heme precursor, δ-aminolevulinic acid (δ-ALA), constricted arterioles with intact endothelium pretreated with phenylephrine; these effects were abolished by removal of the endothelium. CO- and δ-ALA-induced vasoconstrictions were converted to dilations by pretreatment with an inhibitor of NO synthase, Nω-nitro-l-arginine methyl ester, or with Nω-nitro-l-arginine methyl ester and an NO donor, sodium nitroprusside. Furthermore, CO-induced vasoconstriction was prevented by pretreatment with the NO synthase substrate l-arginine. This study shows that exogenous, as well as endogenously formed, CO can promote endothelium-dependent vasoconstriction in isolated gracilis muscle arterioles. Because CO-induced vasoconstriction is abolished by NO synthase blockade and by l-arginine, CO most likely promotes endothelium-dependent vasoconstriction by inhibiting endothelial NO formation.
Glomerular and tubular responses toNG-nitro-l-arginine methyl ester are age dependent in conscious lambs
Authors: Sener Alp , Smith Francine G.
Published: March 2015

The present experiments were carried out to investigate the role of endogenously produced NO in modulating renal function during postnatal maturation under physiological conditions. In conscious, chronically instrumented lambs aged ∼1 ( n= 8) and ∼6 wk ( n = 8) of postnatal life, various parameters of glomerular and tubular function were measured for 1 h before and 1 h after intravenous injection of 20 mg/kg of NG-nitro-l-arginine methyl ester (l-NAME; experiment 1) or its inactive isomerd-NAME ( experiment 2). After administration ofl-NAME to 1-wk-old lambs, glomerular filtration rate (GFR) and filtration factor (FF) decreased by ∼50% at 20 min, remaining decreased at 60 min. In 6-wk-old lambs, GFR and FF remained constant after l-NAME. Proximal fractional Na+reabsorption decreased after l-NAME administration to lambs aged 6 wk, resulting in a prompt natriuresis; this was sustained for 60 min. There were no effects of l-NAME on proximal fractional Na+reabsorption in 1-wk-old lambs. In 6-wk-old lambs, urinary flow rate increased by ∼500%, free water clearance increased by ∼50%, and urinary osmolality decreased by ∼60% afterl-NAME administration; no effects on these variables were measured in 1-wk-old lambs. The diuresis after l-NAME administration to 6-wk-old lambs was unaccompanied by any changes in plasma levels of arginine vasopressin. There were no effects ofd-NAME on any of the measured variables. We conclude that endogenously produced nitric oxide modulates glomerular and tubular function in an age-dependent manner.
Constitutive and permissive roles of nitric oxide activity in embryonic ciliary cells
Authors: Doran Shandra A. , Tran Cam Ha , Eskicioglu Cagla , Stachniak Tev , Ahn Kee-Chan , Goldberg Jeffrey I.
Published: March 2015

Embryos of Helisoma trivolvis exhibit cilia-driven rotation within the egg capsule during development. In this study we examined whether nitric oxide (NO) is a physiological regulator of ciliary beating in cultured ciliary cells. The NO donor S-nitroso- N-acetylpenicillamine (SNAP; 1–1,000 μM) produced a dose-dependent increase in ciliary beat frequency (CBF). In contrast, the nitric oxide synthase (NOS) inhibitor 7-nitroindazole (10 and 100 μM) inhibited the basal CBF and blocked the stimulatory effects of serotonin (100 μM). NO production in response to serotonin was investigated with 4,5-diaminofluorescein diacetate imaging. Although SNAP (100 μM) produced a rise in NO levels in all cells, only 22% of cells responded to serotonin with a moderate increase. The cGMP analog 8-bromo-cGMP (8-Br-cGMP; 0.2 and 2 mM) increased CBF, and the soluble guanylate cyclase inhibitor LY-83583 (10 μM) blocked the cilioexcitatory effects of SNAP and serotonin. These data suggest that NO has a constitutive cilioexcitatory effect in Helisoma embryos and that the stimulatory effects of serotonin and NO work through a cGMP pathway. It appears that in Helisoma cilia, NO activity is necessary, but not sufficient, to fully mediate the cilioexcitatory action of serotonin.
Single-fiber myosin heavy chain polymorphism: how many patterns and what proportions?
Authors: Caiozzo Vincent J. , Baker Michael J. , Huang Karen , Chou Harvey , Wu Ya Zhen , Baldwin Kenneth M.
Published: March 2015

Previous studies have reported the existence of skeletal muscle fibers that coexpress multiple myosin heavy chain isoforms. These surveys have usually been limited to studying the polymorphic profiles of skeletal muscle fibers from a limited number of muscles (i.e., usually <4). Additionally, few studies have considered the functional implications of polymorphism. Hence, the primary objective of this study was to survey a relatively large number of rat skeletal muscle/muscle regions and muscle fibers ( n≈ 5,000) to test the hypothesis that polymorphic fibers represent a larger fraction of the total pool of fibers than do so-called monomorphic fibers, which express only one myosin heavy chain isoform. Additionally, we used Hill's statistical model of the force-velocity relationship to differentiate the functional consequences of single-fiber myosin heavy chain isoform distributions found in these muscles. The results demonstrate that most muscles and regions of rodent skeletal muscles contain large proportions of polymorphic fibers, with the exception of muscles such as the slow soleus muscle and white regions of fast muscles. Several muscles were also found to have polymorphic profiles that are not consistent with the I↔IIA↔IIX↔IIB scheme of muscle plasticity. For instance, it was found that the diaphragm muscle normally contains I/IIX fibers. Functionally, the high degree of polymorphism may 1) represent a strategy for producing a spectrum of contractile properties that far exceeds that simply defined by the presence of four myosin heavy chain isoforms and 2) result in relatively small differences in function as defined by the force-velocity relationship.
Acute sympathoexcitatory action of angiotensin II in conscious baroreceptor-denervated rats
Authors: Xu Ling , Sved Alan F.
Published: March 2015

Angiotensin II (ANG II) has complex actions on the cardiovascular system. ANG II may act to increase sympathetic vasomotor outflow, but acutely the sympathoexcitatory actions of exogenous ANG II may be opposed by ANG II-induced increases in arterial pressure (AP), evoking baroreceptor-mediated decreases in sympathetic nerve activity (SNA). To examine this hypothesis, the effect of ANG II infusion on lumbar SNA was measured in unanesthetized chronic sinoaortic-denervated rats. Chronic sinoaortic-denervated rats had no reflex heart rate (HR) responses to pharmacologically evoked increases or decreases in AP. Similarly, in these denervated rats, nitroprusside-induced hypotension had no effect on lumbar SNA; however, phenylephrine-induced increases in AP were still associated with transient decreases in SNA. In control rats, infusion of ANG II (100 ng · kg−1 · min−1 iv) increased AP and decreased HR and SNA. In contrast, ANG II infusion increased lumbar SNA and HR in sinoaortic-denervated rats. In rats that underwent sinoaortic denervation surgery but still had residual baroreceptor reflex-evoked changes in HR, the effect of ANG II on HR and SNA was variable and correlated to the extent of baroreceptor reflex impairment. The present data suggest that pressor concentrations of ANG II in rats act rapidly to increase lumbar SNA and HR, although baroreceptor reflexes normally mask these effects of ANG II. Furthermore, these studies highlight the importance of fully characterizing sinoaortic-denervated rats used in experiments examining the role of baroreceptor reflexes.
Arterial baroreceptors mediate the inhibitory effect of acute increases in arterial blood pressure on thirst
Authors: Stocker Sean D. , Stricker Edward M. , Sved Alan F.
Published: March 2015

The present study sought to determine whether arterial baroreceptor afferents mediate the inhibitory effect of an acute increase in arterial blood pressure (AP) on thirst stimulated by systemically administered ANG II or by hyperosmolality. Approximately 2 wk after sinoaortic denervation, one of four doses of ANG II (10, 40, 100, or 250 ng · kg−1 · min−1) was infused intravenously in control and complete sinoaortic-denervated (SAD) rats. Complete SAD rats ingested more water than control rats when infused with 40, 100, or 250 ng · kg−1 · min−1 ANG II. Furthermore, complete SAD rats displayed significantly shorter latencies to drink compared with control rats. In a separate group of rats, drinking behavior was stimulated by increases in plasma osmolality, and mean AP was raised by an infusion of phenylephrine (PE). The infusion of PE significantly reduced water intake and lengthened the latencies to drink in control rats but not in complete SAD rats. In all experiments, drinking behavior of rats that were subjected to sinoaortic denervation surgery but had residual baroreceptor reflex function (partial SAD rats) was similar to that of control rats. Thus it appears that arterial baroreceptor afferents mediate the inhibitory effect of an acute increase in AP on thirst stimulated by ANG II or hyperosmolality.
Direct effects of acute hypoxia on the reactivity of peripheral arteries of the chicken embryo
Authors: Ruijtenbeek K. , Kessels C. G. A. , Villamor E. , Blanco C. E. , De Mey J. G. R.
Published: March 2015

In the chicken embryo, acute hypoxemia results in cardiovascular responses, including an increased peripheral resistance. We investigated whether local direct effects of decreased oxygen tension might participate in the arterial response to hypoxemia in the chicken embryo. Femoral arteries of chicken embryos were isolated at 0.9 of incubation time, and the effects of acute hypoxia on contraction and relaxation were determined in vitro. While hypoxia reduced contraction induced by high K+ to a small extent (−21.8 ± 5.7%), contractile responses to exogenous norepinephrine (NE) were markedly reduced (−51.1 ± 3.2%) in 80% of the arterial segments. This effect of hypoxia was not altered by removal of the endothelium, inhibition of NO synthase or cyclooxygenase, or by depolarization plus Ca2+ channel blockade. When arteries were simultaneously exposed to NE and ACh, hypoxia resulted in contraction (+49.8 ± 9.3%). Also, relaxing responses to ACh were abolished during acute hypoxia, while the vessels became more sensitive to the relaxing effect of the NO donor sodium nitroprusside (pD2: 5.81 ± 0.21 vs. 5.31 ± 0.27). Thus, in chicken embryo femoral arteries, acute hypoxia blunts agonist-induced contraction of the smooth muscle and inhibits stimulated endothelium-derived relaxation factor release. The consequences of this for in vivo fetal hemodynamics during acute hypoxemia depend on the balance between vasomotor influences of circulating catecholamines and those of the endothelium.
Ingestive behavior and body temperature during the ovarian cycle in normotensive and hypertensive rats
Authors: Rashotte Michael E. , Ackert Allison M. , Overton J. Michael
Published: March 2015

The relationship between ingestive behavior (eating + drinking) and core body temperature (Tb) in naturally cycling female rats was compared in a normotensive strain (Sprague-Dawley; SD) and a hypertensive strain reputed to have chronically elevated Tb (spontaneously hypertensive rats; SHR). Tb (by telemetry) and ingestive behavior (automated recording) were quantified every 30 s. Ingestive behavior and Tb were related on all days of the ovarian cycle in both strains, but the strength of that relationship was reduced on the day of estrus (E) compared with nonestrous days. Several strain differences in Tb were found as well. In SHR, dark-phase Tb was elevated on E, whereas SD remained at the lower nonestrous values. Fluctuations in dark-phase Tb were correlated with ingestive behavior in both strains but had greater amplitude in SHR except on E. Short-term fasting or sucrose availability did not eliminate elevated dark-phase Tb on E in SHR. We propose that estrus-related changes unique to SHR may indicate heightened thermal reactivity to hormonal changes, ingestive behavior, and general locomotor activity.
Predominant activation of endothelin-dependent cardiac hypertrophy by norepinephrine in rat left ventricle
Authors: Moser Lutz , Faulhaber Jörg , Wiesner Rudolf J. , Ehmke Heimo
Published: March 2015

Locally released endothelin (ET)-1 has been recently identified as an important mediator of cardiac hypertrophy. It is still unclear, however, which primary stimulus specifically activates ET-dependent signaling pathways. We therefore examined in adult rats ( n = 51) the effects of a selective ETAreceptor antagonist in experimental models of cardiac hypertrophy, in which myocardial growth is predominantly initiated by a single primary stimulus. Rats were exposed to mechanical overload (ascending aortic stenosis), increased levels of circulating ANG II (ANG II infusion combined with hydralazine), or adrenergic stimulation (infusion of norepinephrine in a subpressor dose) for 7 days. All experimental treatments significantly increased left ventricular weight/body weight ratios compared with untreated rats, whereas systolic left ventricular peak pressure was increased only after ascending aortic stenosis. ETAreceptor blockade exclusively reduced norepinephrine-induced cardiac hypertrophy and atrial natriuretic peptide gene expression. Blood pressure levels and heart rates remained unaffected during ETAreceptor blockade in all experimental groups. These data indicate that in rat left ventricle, the ET-dependent signaling pathway leading to early development of cardiac hypertrophy and fetal gene expression is primarily activated by norepinephrine.