bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of inhibition of MAO and COMT on intrarenal dopamine and serotonin and on renal function
Authors: Wang Yongqing , Berndt Theresa J. , Gross Jennifer M. , Peterson Michael A. , So Mathew J. , Knox Franklyn G.
Published: December 2017

The purpose of the present investigation was to study the effects of inhibition of monoamine oxidase (MAO) and/or catechol- O-methyltransferase (COMT), enzymes involved in the degradation of dopamine (DA) and serotonin (5-HT), on intrarenal DA and 5-HT, as reflected in the renal interstitial fluid (RIF) microdialysate and urine, and on renal function. Inhibition of MAO selectively increased RIF 5-HT from 3.16 ± 0.38 to 8.03 ± 1.83 pg/min ( n = 7, P < 0.05), concomitant with decreases in mean arterial blood pressure and glomerular filtration rate (2.09 ± 0.18 to 1.57 ± 0.22 ml/min, n = 7, P < 0.05). Inhibition of COMT significantly increased RIF DA (3.47 ± 0.70 to 8.68 ± 1.96 pg/min, n = 9, P < 0.05), urinary DA (2.00 ± 0.16 to 2.76 ± 0.26 ng/min, n = 9, P < 0.05), and absolute excretion of sodium (6.42 ± 2.00 to 9.82 ± 1.62 μmol/min, n = 10, P < 0.05). Combined inhibition of MAO and COMT significantly increased RIF DA, urinary DA, and urinary 5-HT, which was accompanied with increases in urine flow rate, and absolute (3.03 ± 0.59 to 8.40 ± 1.61 μmol/min, n = 9, P < 0.01) and fractional excretion of sodium. We conclude that inhibition of MAO selectively increases RIF 5-HT. COMT appears to be more important than MAO in the metabolism of intrarenal DA. Physiological increases in intrarenal DA/5-HT induced by inhibition of their degrading enzymes are accompanied with significant alterations of renal function.
Glucocorticoid regulation of angiotensin-converting enzyme in primary culture of adult cardiac fibroblasts
Authors: Barreto-Chaves M. L. M. , Anéas I. , Krieger J. E.
Published: December 2017

The effect of dexamethasone on angiotensin-converting enzyme (ACE) in primary culture of adult cardiac fibroblasts was analyzed in this study. ACE is central to cardiac remodeling in conditions such as myocardial infarction (MI). Some studies indicate that glucocorticoids are often increased post-MI, whereas other studies suggest that glucocorticoids stimulate ACE activity in various cell types. Most cardiac cells are fibroblasts, which have an important function in cardiac remodeling. Therefore, we studied the effects of glucocorticoids on ACE activity and mRNA levels in primary cultures of adult rat cardiac fibroblasts. Steady-state ACE activity was very low, but it increased sixfold with dexamethasone (1 μM for 48 h) treatment. ACE activation occurred within 12 h and peaked at 96 h, after treatment. RNase-protection assays revealed an associated threefold increase ( P < 0.05) in ACE mRNA. Dexamethasone's stimulatory effect was abolished by an RNA synthesis inhibitor (actinomycin D, 5 μg/ml) but was potentiated by a protein synthesis inhibitor (cycloheximide, 5 μg/ml). The glucocorticoid-mediated response appears to be specific, because mineralocorticoid treatment did not alter ACE activity. These findings indicate that both transcriptional and posttranscriptional mechanisms are involved in glucocorticoid regulation of ACE expression in rat cardiac fibroblasts.
CYP4A1 antisense oligonucleotide reduces mesenteric vascular reactivity and blood pressure in SHR
Authors: Wang Mong-Heng , Zhang Fan , Marji Jackleen , Zand Barbara A. , Nasjletti Alberto , Laniado-Schwartzman Michal
Published: December 2017

The cytochrome P-450 4A (CYP4A)-derived arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) affects renal tubular and vascular functions and has been implicated in the control of arterial pressure. We examined the effect of antisense oligonucleotide (ODN) to CYP4A1, the low K m arachidonic acid ω-hydroxylating isoform, on vascular 20-HETE synthesis, vascular reactivity, and blood pressure in the spontaneously hypertensive rat (SHR). Administration of CYP4A1 antisense ODN decreased mean arterial blood pressure from 137 ± 3 to 121 ± 4 mmHg ( P < 0.05) after 5 days of treatment, whereas treatment with scrambled antisense ODN had no effect. Treatment with CYP4A1 antisense ODN reduced the level of CYP4A-immunoreactive proteins along with 20-HETE synthesis in mesenteric arterial vessels. Mesenteric arteries from rats treated with antisense ODN exhibited decreased sensitivity to the constrictor action of phenylephrine (EC50 0.69 ± 0.17 vs. 1.77 ± 0.40 μM). Likewise, mesenteric arterioles from antisense ODN-treated rats revealed attenuation of myogenic constrictor responses to increases of transmural pressure. The decreased vascular reactivity and myogenic responses were reversible with the addition of 20-HETE. These data suggest that CYP4A1-derived 20-HETE facilitates myogenic constrictor responses in the mesenteric microcirculation and contributes to pressor mechanisms in SHR.
Manipulation of androgens causes different energetic responses to cold in 60- and 40-day-old male rats
Authors: Gomez Francisca , Dallman Mary F.
Published: December 2017

Previous studies suggested that adults respond differently than pubertal male rats to cold stress. To test the role of androgens in this difference, we adrenalectomized and replaced with corticosterone either 60- or 40-day-old male rats, then sham gonadectomized (Intact), gonadectomized (GDX), or GDX and replaced with testosterone (T; GDX+T) or dihydrotestosterone (DHT). One-half remained at room temperature (RT), and one-half lived in cold for 5 days. Cold reduced T in adult but not in pubertal Intacts. In 60-day-old rats, GDX with or without T replacement had minor effects on body weight (BW) and food intake (FI) at RT and cold. In 40-day-old rats at RT, androgens had slight effects; however, androgens affected almost all variables in cold. Separation of 40-day-old T-treated rats into two groups (moderate T levels, 1.4 ng/ml; high T levels, 1.9 ng/ml) revealed major differences between the groups. Moderate T (and DHT) prevented cold-induced loss of BW and increased FI. No T and high T induced decreased BW and FI in cold. We conclude that at 40 days of age, partial resistance to stress-induced reduction of T and high sensitivity to small changes in T have markedly positive effects on threatened energy balance.
ANP, BNP, and CNP enhance bradycardic responses to cardiopulmonary chemoreceptor activation in conscious sheep
Authors: Thomas Colleen J. , May Clive N. , Sharma Atul D. , Woods Robyn L.
Published: December 2017

We demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia to intravenous serotonin [5-hydroxytryptamine (5-HT)] (von Bezold-Jarisch reflex) in rats. To determine whether 1) ANP affects this cardiopulmonary vagal reflex in another species and 2) B-type (BNP) and C-type (CNP) natriuretic peptides share with ANP the ability to modulate this reflex, we used intravenous phenylbiguanide (PBG), a 5-HT3agonist, as the stimulus to evoke a von Bezold-Jarisch reflex (dose-related, reproducible bradycardia) in conscious adult sheep ( n = 5). Three doses of PBG (13 ± 3, 20 ± 3, and 31 ± 4 μg/kg) injected into the jugular vein caused reflex cardiac slowing of −7 ± 1, −15 ± 2, and −36 ± 3 beats/min, respectively, under control conditions. These doses of PBG were repeated during infusions of ANP, BNP, or CNP (10 pmol · kg−1 · min−1 iv), or vehicle (normal saline). Each of the natriuretic peptides significantly ( P < 0.05) enhanced the sensitivity of bradycardic responses to PBG by 94 ± 8% (ANP), 142 ± 55% (BNP), and 61 ± 16% (CNP). Thus not only did ANP sensitize cardiopulmonary chemoreceptor activation in a species with resting heart rate close to that in humans, but BNP and CNP also enhanced von Bezold-Jarisch reflex activity in conscious sheep.
Differential control of intrarenal blood flow during reflex increases in sympathetic nerve activity
Authors: Leonard Bridget L. , Malpas Simon C. , Denton Kate M. , Madden Anna C. , Evans Roger G.
Published: December 2017

The role of renal sympathetic nerve activity (RSNA) in the physiological regulation of medullary blood flow (MBF) remains ill defined, yet regulation of MBF may be crucial to long-term arterial pressure regulation. To investigate the effects of reflex increases in RSNA on intrarenal blood flow distribution, we exposed pentobarbital sodium-anesthetized, artificially ventilated rabbits ( n = 7) to progressive hypoxia while recording RSNA, cortical blood flow (CBF), and MBF using laser-Doppler flowmetry. Another group of animals with denervated kidneys ( n = 6) underwent the same protocol. Progressive hypoxia (from room air to 16, 14, 12, and 10% inspired O2) significantly reduced arterial oxygen partial pressure (from 99 ± 3 to 65 ± 2, 51 ± 2, 41 ± 1, and 39 ± 2 mmHg, respectively) and significantly increased RSNA (by 8 ± 3, 44 ± 25, 62 ± 21, and 76 ± 37%, respectively, compared with room air) without affecting mean arterial pressure. There were significant reductions in CBF (by 2 ± 1, 5 ± 2, 11 ± 3, and 14 ± 2%, respectively) in intact but not denervated rabbits. MBF was unaffected by hypoxia in either group. Thus moderate reflex increases in RSNA cause renal cortical vasoconstriction, but not at vascular sites regulating MBF.
Substance P and NPY differentially potentiate ATP and adrenergic stimulated vasopressin and oxytocin release
Authors: Kapoor John R. , Sladek Celia D.
Published: December 2017

The supraoptic nuclei are innervated by the A1 neurons of the caudal ventrolateral medulla. Substances colocalized in the A1 terminals include norepinephrine (NE), substance P (SP), ATP, and neuropeptide Y (NPY). ATP, acting at P2xreceptors, caused rapid and unsustained stimulation of vasopressin (VP) and oxytocin (OT) release from perifused explants of the hypothalamo-neurohypophysial system. SP elicited a concentration-dependent stimulation of VP and OT release that was large and sustained compared with other stimuli. ATP, but not phenylephrine (PE, α1-adrenergic agonist), augmented the response to SP (1 μM). In contrast, NPY did not alter basal nor ATP-induced VP or OT release, but it did cause sustained potentiation of PE-induced VP and OT release. The Y1-agonist, [Leu31,Pro34]-NPY, increased VP and OT release, suggesting that the ineffectiveness of NPY reflects opposing actions at pre- and postsynaptic receptors. However, [Leu31,Pro34]-NPY did not potentiate hormone responses to ATP or PE. The differential responses to these colocalized neurotransmitters and neuropeptides illustrate the range of potential responses that stimulation of this pathway might elicit from supraoptic neurons.
Chemical stimulation of the dorsomedial hypothalamus elevates plasma ACTH in conscious rats
Authors: Bailey Timothy W. , Dimicco Joseph A.
Published: December 2017

The hallmark neuroendocrine response to stress is increased plasma ACTH. Inhibition of neurons in the region of the dorsomedial hypothalamus (DMH) attenuates experimental air stress-induced elevation of heart rate (HR), mean arterial pressure (MAP), and plasma ACTH. We hypothesized that, under basal conditions, stimulation of the DMH would mimic the neuroendocrine and cardiovascular response to air stress. We examined the effects of unilateral microinjection (100-nl vol) of bicuculline methiodide (BMI, 10 pmol), kainate (KA, 1 or 3 pmol), and N-methyl-d-aspartate (5 pmol) into the DMH or the paraventicular nucleus (PVN) on HR, MAP, locomotor activity, and plasma ACTH in conscious rats. Chemical stimulation of the DMH with KA or BMI produced increased locomotor activity and effects on HR, MAP, and plasma ACTH that together mimicked the pattern seen in experimental stress. Similar treatment in the PVN produced only small increases in MAP. Thus activation of neurons in the region of the DMH results in increased secretion of ACTH along with other changes typically seen in experimental stress.
Chronic exercise alters caudal hypothalamic regulation of the cardiovascular system in hypertensive rats
Authors: Kramer Jeffery M. , Beatty Joseph A. , Little Hugh R. , Plowey Edward D. , Waldrop Tony G.
Published: December 2017

Previous studies have documented a deficit in the GABA neurotransmitter system within the caudal hypothalamus (CH) of spontaneously hypertensive rats (SHR). The reduction in inhibitory influence on this cardiovascular excitatory brain region is associated with an increased neuronal activity and resting blood pressure. The purpose of this study was to determine if chronic treadmill and wheel-running activities alter the ability of the CH to regulate cardiovascular function. SHR were exercised on a treadmill (5 times/wk) at moderate intensity or allowed free access to running wheels (7 days/wk) for a period of 10 wk. Resting blood pressures were obtained before and after the exercise training periods. After the exercise period, rats were anesthetized and microinjection experiments were performed. Treadmill-trained SHR exhibited a significantly blunted developmental rise in resting blood pressure after 10 wk of exercise. A similar yet less marked effect was observed in wheel-run rats. Microinjection of the GABA synthesis inhibitor 3-mercaptopropionic acid (3-MP) into the CH of nonexercised SHR did not produce any change in arterial pressure. In contrast, microinjection of 3-MP into the CH produced significant increases in blood pressure and heart rate in exercised SHR. These results demonstrate that exercise training can alter CH cardiovascular regulation in hypertensive rats and therefore may play a role in increasing cardiovascular health.
Effects of maturation and acute hypoxia on receptor-IP3coupling in ovine common carotid arteries
Authors: Angeles Danilyn M. , Williams James , Purdy Ralph E. , Zhang Lubo , Pearce William J.
Published: December 2017

Whereas previous studies have established that many mechanisms mediating pharmacomechanical coupling are subject to regulation, evidence of physiological regulation of the coupling efficiency between receptor activation and second-messenger production is scarce. The present studies address the hypothesis that acute hypoxia and maturation can influence the mass of second-messenger production for each activated agonist-bound receptor (“receptor gain”). For this assessment, receptor density and agonist affinity values were used to calculate 5-hydroxytryptamine (5-HT) concentrations that would produce standardized numbers of bound receptors (8.5 fmol/mg protein) in each experimental group and thus minimize effects of age or hypoxia on receptor density or agonist affinity. After 3 min of exposure to these 5-HT concentrations, normoxic magnitudes of contraction were similar (as %potassium maxima) in fetal (50 ± 14%) and adult (40 ± 9%) arteries, but hypoxia (Po2≈ 9–12 Torr for 30 min) depressed contractile tensions with a significantly different time course and magnitude in fetal (30 ± 10%) and adult (17 ± 11%) arteries ( P < 0.05). Basal inositol 1,4,5-trisphosphate (IP3) values (in pmol/mg protein) were significantly greater in fetal (94 ± 16) than in adult (44 ± 6) arteries, and integrated areas above baseline for the IP3time courses (in nmol-s/mg protein) were significantly greater in fetal than in adult arteries both in normoxic (14.3 ± 1.8 vs. 9.1 ± 1.6) and hypoxic (15.0 ± 2.1 vs. 8.6 ± 1.2) conditions ( P < 0.05). Hypoxia altered the IP3time courses both in the fetus and the adult but had no significant effect on IP3mobilization or receptor gain. These data demonstrate that for the 5-HT2areceptor predominant in this preparation, receptor gain can be experimentally determined, is not influenced by acute hypoxia, but is greater in fetal than in adult ovine carotid arteries.
Effect of water restriction on feeding and metabolism in dairy cows
Authors: Burgos Martine Steiger , Senn Markus , Sutter Franz , Kreuzer Michael , Langhans Wolfgang
Published: December 2017

We investigated how lactating cows are able to cope with a sustained water restriction. In experiment 1, body weight and meal patterns were recorded with ad libitum access to water (baseline) and during 8 days of 25 and 50% restriction of drinking water relative to ad libitum intake. In experiment 2, indirect calorimetry was combined with nitrogen and energy balance and plasma hormone and metabolite measurements to assess the effects of 50% water restriction on digestion and metabolism. In experiment 1, food intake and body weight declined during the first 3 days of water restriction depending on the restriction level and stabilized thereafter at a lower level. The daily food intake reduction with 50% water restriction was entirely due to a reduction of meal size. The size of the first meal on every day was markedly (>50%) reduced with 25 and 50% water restriction. In experiment 2, urea concentrations in milk and blood as well as plasma sodium and hematocrit were increased by 50% water restriction. Energy balance was not affected by 50% water restriction, but nitrogen balance became negative, because, relative to intake, nitrogen excretion via urine and milk was higher. The lower energy intake during 50% water restriction was compensated by a lower milk production, a higher digestibility of organic matter and energy, and, apparently, a more efficient energy use. Through these changes and a preserved water balance, the cows reached a new equilibrium at a lower water turnover level, which enabled them to cope with a sustained drinking water restriction of 50%.
Topical application of the phospholipid growth factor lysophosphatidic acid promotes wound healing in vivo
Authors: Balazs Louisa , Okolicany Juraj , Ferrebee Mike , Tolley Betsy , Tigyi Gabor
Published: December 2017

The lipid mediator lysophosphatidic acid (LPA) regulates cell proliferation and enhances cell motility in vitro, both of which are important events in wound healing. To evaluate the effects of LPA in vivo, it was applied to a full-thickness wound of rat skin. LPA in micromolar concentrations, or solvent, was applied daily. Animals were killed at 1, 3, 6, and 9 days after wounding and processed for histological evaluation, including hematoxylin-eosin staining and histochemical markers for macrophage-histiocytes, proliferating cells, and capillary endothelial cells. LPA treatment accelerated wound closing and increased neoepithelial thickness. Cytological evaluation showed no evidence for a secondary inflammation-mediated injury, infection, or increased keloid formation. Whereas LPA caused only a modest dose-dependent increase in proliferating cells, a marked increase in the immigration of histiocyte-macrophage cells was observed as early as day 1. The peaks of several cytological features and immunohistological markers preceded those of the untreated side. Our data suggest that exogenously applied LPA in this model promotes healing and that macrophage-histiocytes are the primary LPA-responsive cells in vivo.
Acute changes in the response to peripheral leptin with alteration in the diet composition
Authors: Lin L. , Martin R. , Schaffhauser A. O. , York D. A.
Published: December 2017

Dietary induced obesity in rodents is associated with a resistance to leptin. We have investigated the hypothesis that dietary fat per se alters the feeding response to peripheral leptin in rats that were fed either their habitual high- or low-fat diet or were naively exposed to the alternative diet. Osborne-Mendel rats were adapted to either high- or low-fat diet. Food-deprived rats were given either leptin (0.5 mg/kg body wt ip) or saline, after which they were provided with either their familiar diet or the alternative diet. Food intake of rats adapted and tested with the low-fat diet was reduced 4 h after leptin injection, whereas rats adapted and tested with a high-fat diet did not respond to leptin. Leptin was injected again 1 and 5 days after the high-fat diet-adapted rats were switched to the low-fat diet. Leptin reduced the food intake on both days. In contrast, when low-fat diet-adapted rats were switched to a high-fat diet, the leptin inhibitory response was present on day 1 but not observed on day 5. Peripheral injection of leptin increased serum corticosterone level and decreased hypothalamic neuropeptide Y mRNA expression in rats fed the low-fat but not the high-fat diet for 20 days. The data suggest that dietary fat itself, rather than obesity, may induce leptin resistance within a short time of exposure to a high-fat diet.
Effects of 17β-estradiol on levels and distribution of metallothionein and zinc in squirrelfish
Authors: Thompson E. David , Olsson Per-Erik , Mayer Gregory D. , Haux Carl , Walsh Patrick J. , Burge Erin , Hogstrand Christer
Published: December 2017

Females of the squirrelfish family ( Holocentridae) accumulate higher levels of zinc in the liver than any other known animal. This zinc accumulation is made possible by high expression of the zinc-binding protein, metallothionein (MT). In the present study, the squirrelfish (Holocentrus ascensionis) MT cDNA was cloned and sequenced. The deduced amino acid sequence was very similar to other teleost MT. The role of estrogens on zinc metabolism was investigated by injecting male and immature female squirrelfish with 17β-estradiol (E2). E2treatment triggered transient increases in plasma zinc and vitellogenin (VTG) levels, and both of these variables showed very similar time courses. These results suggest that E2is responsible for the large hepatoovarian translocation of zinc observed in female squirrelfish and that VTG might be a vehicle for zinc. E2did not directly alter the levels of zinc or MT mRNA in the liver. However, the hepatic MT protein concentration increased differentially in the nuclear fraction. Thus E2is probably responsible for the association of MT with the nuclear fraction previously observed in untreated mature female squirrelfish.
Basal forebrain acetylcholine release during REM sleep is significantly greater than during waking
Authors: Vazquez Jacqueline , Baghdoyan Helen A.
Published: December 2017

Cholinergic neurons of the basal forebrain supply the neocortex with ACh and play a major role in regulating behavioral arousal and cortical electroencephalographic activation. Cortical ACh release is greatest during waking and rapid eye movement (REM) sleep and reduced during non-REM (NREM) sleep. Loss of basal forebrain cholinergic neurons contributes to sleep disruption and to the cognitive deficits of many neurological disorders. ACh release within the basal forebrain previously has not been quantified during sleep. This study used in vivo microdialysis to test the hypothesis that basal forebrain ACh release varies as a function of sleep and waking. Cats were trained to sleep in a head-stable position, and dialysis samples were collected during polygraphically defined states of waking, NREM sleep, and REM sleep. Results from 22 experiments in four animals demonstrated that means ± SE ACh release (pmol/10 min) was greatest during REM sleep (0.77 ± 0.07), intermediate during waking (0.58 ± 0.03), and lowest during NREM sleep (0.34 ± 0.01). The finding that, during REM sleep, basal forebrain ACh release is significantly elevated over waking levels suggests a differential role for basal forebrain ACh during REM sleep and waking.
Lesion of the perinuclear zone attenuates cardiac sensitivity of vasopressinergic supraoptic neurons
Authors: Grindstaff Regina R. , Cunningham J. Thomas
Published: December 2017

Discrete stretch of the caval-atrial junction decreases the activity of vasopressin-secreting neurons in the supraoptic nucleus (SON). The perinuclear zone (PNZ) of the SON is necessary for inhibition of vasopressin neurons following an increase in blood pressure. To determine whether the PNZ is necessary for cardiopulmonary regulation of vasopressin neurons, male rats received three unilateral injections of the excitotoxin ibotenic acid ( n = 9) or phosphate-buffered saline vehicle ( n = 10) into the PNZ. Extracellular activity of antidromically identified phasic vasopressin neurons in the ipsilateral SON was recorded. Of the 26 neurons recorded from vehicle-injected rats 26 were inhibited by an increase in blood pressure and 22 of those neurons were sensitive to caval-atrial distension. Of the neurons recorded from PNZ-lesion rats, only 12 of 29 were inhibited by an increase in blood pressure ( P < 0.05), and only 11 neurons were sensitive to caval-atrial stretch ( P < 0.05). Functional lesion of the PNZ significantly attenuates both arterial and cardiopulmonary baroreceptor-mediated inhibition of supraoptic vasopressin neurons, suggesting that the PNZ is a necessary component of both pathways.
Hormonal regulation of chicken intestinal NHE and SGLT-1 activities
Authors: De La Horra Maria Carmen , Cano Mercedes , Peral Maria José , Calonge Maria Luisa , Ilundáin Anunciación Ana
Published: December 2017

The effects of aldosterone and arginine vasotocin (AVT) on intestinal Na+/H+exchange (NHE) and Na+-sugar cotransport (SGLT-1) activities have been investigated using brush-border membrane vesicles isolated from Hubbard chicken small and large intestines, and they were compared with those induced by either Na+depletion or dehydration. Na+depletion was induced by feeding the chickens with either a low- or a high-Na+diet for either 0.5, 1, 2, 4, or 8 days. Ileal and colonic NHE2 activity increased with the duration of the Na+depletion, whereas that of intestinal SGLT-1 decreased, reaching a plateau after 2 days of treatment. Three-hour incubation of the intestine with aldosterone produced the same effects on NHE activity as does Na+depletion, without altering SGLT-1 activity. However, 3-h incubation of the intestine with AVT increased intestinal SGLT-1 activity, without affecting intestinal NHE activity. It is concluded that aldosterone regulates apical ileal and colonic NHE2 activity, whereas that of SGLT-1 is regulated by AVT.
Purinergic contribution to circulatory, metabolic, and adrenergic responses to acute hypoxemia in fetal sheep
Authors: Giussani Dino A. , Gardner David S. , Cox David T. , Fletcher Andrew J. W.
Published: December 2017

This study investigated the effects on femoral vascular resistance, blood glucose and lactate levels, and plasma catecholamine concentrations of fetal treatment with an adenosine receptor antagonist during acute hypoxemia in fetal sheep during late gestation.

Under anesthesia, seven fetal sheep were instrumented between 117 and 118 days gestation (term is ∼145 days) with vascular and amniotic catheters and an ultrasonic probe around a femoral artery. Six days after surgery, all fetuses were randomly subjected to a 3-h experiment consisting of 1 h of normoxia, 1 h of hypoxemia, and 1 h of recovery. This was done during either intravenous infusion of vehicle or the adenosine receptor antagonist [8-( p-sulfophenyl)-theophylline; 8-SPT] dissolved in vehicle. During vehicle infusion, all fetuses responded to hypoxemia with bradycardia, an increase in arterial blood pressure, and femoral vasoconstriction. Increases in blood glucose and lactate concentrations and in plasma epinephrine and norepinephrine concentrations also occurred in all fetuses during hypoxemia. Fetal treatment with 8-SPT markedly attenuated the bradycardic, hypertensive, vasoconstrictor, glycemic, and adrenergic responses to hypoxemia, but it did not affect the increase in blood lactate concentrations during hypoxemia.

These data show that adenosine is involved in the mechanisms mediating fetal cardiovascular, metabolic, and adrenergic responses to hypoxemia in fetal sheep. Fetal treatment with 8-SPT mimics the effects of carotid sinus nerve section on fetal cardiovascular function during hypoxemia, suggesting a role for adenosine in mediating fetal cardiovascular chemoreflexes.
Effects of orphanin FQ on central dopaminergic neuronal activities and prolactin secretion
Authors: Shieh Kun-Ruey , Pan Jenn-Tser
Published: December 2017

Effects of orphanin FQ (OFQ) on central dopaminergic (DA) neurons and serum prolactin (PRL) were examined in ovariectomized, estrogen-primed Sprague-Dawley rats. The activities of central DA neurons, including the tuberoinfundibular (TI), nigrostriatal, mesolimbic, and incertohypothalamic ones, were determined by measuring the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine, in their projection regions in the brain by HPLC plus electrochemical detection. Intracerebroventricular administration of OFQ lowered DOPAC levels in the median eminence (ME), striatum, nucleus accumbens, and hypothalamic paraventricular nucleus in a dose (0.01–10 μg)- and time (30–90 min)-dependent manner. In contrast, OFQ increased DOPAC in the suprachiasmatic nucleus and had no effect in the periventricular nucleus. Serum PRL levels exhibited a typical inverse relationship with the activity of TIDA neurons, as determined by DOPAC levels in the ME. In the afternoon, we observed an endogenous decrease of ME DOPAC level accompanied by a PRL surge in estrogen-primed female rats. Although OFQ caused further decrease of ME DOPAC in the afternoon, it failed to augment the PRL surge level. Although pretreatment of an antisense oligodeoxynucleotide against the opioid receptor-like receptor gene had no effect on basal ME DOPAC levels in the morning or afternoon, it attenuated the afternoon PRL surge. Furthermore, it blocked the effects of exogenous OFQ on ME DOPAC and serum PRL levels, whereas the sense or missense oligodeoxynucleotide had no effect. These results indicate that OFQ and its receptors may be involved in the regulation of central DA neuronal activity and PRL secretion.
Myocardial adrenergic and cholinergic receptor function in hypoxia: correlation with O2 transport in exercise
Authors: Favret Fabrice , Richalet Jean-Paul , Henderson Kyle K. , Germack Renée , Gonzalez Norberto C.
Published: December 2017

The time course of changes in rat myocardial α1- and β-adrenoceptors and of muscarinic cholinergic (M-Ach) receptor characteristics was studied parallel with the changes in exercise systemic O2 transport during a 21-day period of hypoxia (barometric pressure 380 Torr) to assess the effects of receptor modification during acclimatization on maximal exercise capacity. Hypoxia resulted in polycythemia, pulmonary hypertension, right ventricular hypertrophy, and transient left ventricular weight loss. Maximal O2 consumption at 30 min of hypoxia was reduced to 60% of the normoxic value and remained unchanged. This was partly due to a gradual decrease in maximal cardiac output and heart rate (HRmax), which offset the increase in blood O2 content. HRmax correlated positively ( r = 0.994) with β-adrenoceptor density and negatively ( r = −0.964) with M-Ach-receptor density, suggesting that HRmax reduction results from intrinsic changes in myocardial receptor characteristics leading to reduced responses to adrenergic stimulation and elevated responses to cholinergic stimulation. α-Adrenoceptor density in both ventricles increased initially to eventually fall below normoxic values. The dissociation between the different patterns of right and left ventricular weight and the similar pattern of α-adrenoceptor change in both ventricles do not support a role for these receptors on right ventricular myocardial hypertrophy.
Transfer of n–3 and n–6 polyunsaturated fatty acids from yolk to embryo during development of the king penguin
Authors: Decrock Frederic , Groscolas René , McCartney Ruth J. , Speake Brian K.
Published: December 2017

This study examines the transfer of lipids from the yolk to the embryo of the king penguin, a seabird with a high dietary intake of n–3 fatty acids. The concentrations of total lipid, triacylglycerol (TAG), and phospholipid (PL) in the yolk decreased by ∼80% between days 33 and 55 of development, indicating intensive lipid transfer, whereas the concentration of cholesteryl ester (CE) increased threefold, possibly due to recycling. Total lipid concentration in plasma and liver of the embryo increased by twofold from day 40 to hatching due to the accumulation of CE. Yolk lipids contained high amounts of C20–22n–3 fatty acids with 22:6(n–3) forming 4 and 10% of the fatty acid mass in TAG and PL, respectively. Both TAG and PL of plasma and liver contained high proportions of 22:6(n–3) (∼15% in plasma and >20% in liver at day 33); liver PL also contained a high proportion of 20:4(n–6) (14%). Thus both 22:6(n–3) and 20:4(n–6), which are, respectively, abundant and deficient in the yolk, undergo biomagnification during transfer to the embryo.
An 1H-MRS evaluation of the phosphocreatine/creatine pool (tCr) in human muscle
Authors: Trump Mark. E. , Hanstock Christopher C. , Allen Peter S. , Gheorghiu Daniel , Hochachka Peter W.
Published: December 2017

The human gastrocnemius was examined with and without creatine supplementation under the conditions of rest, ischemic fatigue (IF), and recovery to perturb the pool sizes and equilibrium between phosphocreatine (PCr) and creatine (Cr).1H- and 31P-magnetic resonance spectroscopy (MRS) were used to examine the total creatine (tCr) pool in each of the metabolic states. 31P-MRS monitored the depletion of the PCr peak during IF to <5% of that at rest. 1H-MRS focused on the tCr methyl peak at 3.02 ppm (dipolar coupled triplet), at which point it was expected that the triplet peak intensity would be similar both in IF and rest. Initial 1H-MRS data showed the peak intensity during IF decreased, suggesting a change in tCr pool size. Subsequent studies of transverse relaxation time (T2) revealed that this decline was primarily due to a more rapid T2 decay of the tCr peak in IF (T2 ∼40 ms) compared with at rest (T2 ∼162 ms). Because Cr is the major contributor to tCr in IF, it is possible that there is a pool of Cr displaying reduced mobility in vivo. Moreover, the residual dipolar coupled triplet observed at rest collapsed into a broad singlet during IF, suggestive of significant changes in the ordered environment experienced at rest for PCr compared with when it is converted to Cr during IF. In addition, these data suggest that in 1H-MRS studies whose goals include quantitative estimates of tCr pool sizes, standardized metabolic conditions or careful T2 evaluations will be required.
A comparison of ovariectomy models for estrogen studies
Authors: Davidge Sandra T. , Zhang Yunlong , Stewart Ken G.
Published: December 2017

Many estrogen-replacement studies use ovariectomized animals as controls. However, ovariectomy greatly increases body weight and can enhance the peripheral synthesis of estrogen. Tamoxifen is commonly used as an antiestrogen, but it may elicit mixed agonist or antagonist actions. The aim of our study was to compare vascular function in mesenteric arteries among groups of rats with low estradiol levels. The groups ( n = 5, each) of Sprague-Dawley rats were cycling (diestrus), ovariectomized (OVX), OVX + tamoxifen (OVX-T), OVX + 4-hydroxyandrostene-3,17-dione, an aromatase inhibitor (OVX-A) to prevent peripheral synthesis of estrogen, and control-fed OVX to prevent excess weight gain. Body weight was significantly elevated in only the non-control-fed OVX group. Estrogen levels were significantly greater in the cycling rats compared with the other groups, whereas uterine weights were significantly reduced in only the OVX-A and control-fed OVX groups. Methacholine relaxation was blunted only in the OVX-A and control-fed OVX groups, suggesting a possible estrogenic influence in the non-control-fed OVX and OVX-T groups. These data indicate the potential for confounding factors to decrease the efficacy of OVX controls.
Functioning of the rat circadian system is modified by light applied in critical postnatal days
Authors: Canal-Corretger M. M. , Vilaplana J. , Cambras T. , Díez-Noguera A.
Published: December 2017

Lighting conditions influence biological clocks. The present experiment was designed to test the presence of a critical window of days during the lactation stage of the rat in which light has a decisive role on the development of the circadian system. Rats were exposed to 4, 8, or 12 days of constant light (LL) during the first days of life. Their circadian rhythm was later studied under LL and constant darkness. The response to a light pulse was also examined. Results show that the greater the number of LL days during lactation, the stronger the rhythm under LL and the smaller the phase shift due to the light pulse. These responses are enhanced when rats are exposed to LL days around postnatal day 12. A mathematical model was built to explain the responses of the circadian system with respect to the timing of LL during lactation, and we deduced that between postnatal days 10 to 20there is a critical period of sensitivity to light; consequently, exposure to LL during this time modifies the circadian organization of the motor activity.
Abnormal renal medullary response to angiotensin II in SHR is corrected by long-term enalapril treatment
Authors: Dukacz Stephen A. W. , Feng Ming-Guo , Yang Lu-Fang , Lee Robert M. K. W. , Kline Robert L.
Published: December 2017

This study tested the hypotheses that renal medullary blood flow (MBF) in spontaneously hypertensive rats (SHR) has enhanced responsiveness to angiotensin (ANG) II and that long-term treatment with enalapril can correct this. MBF, measured by laser Doppler flowmetry in anesthetized rats, was not altered significantly by ANG II in Wistar-Kyoto (WKY) rats, but was reduced dose dependently (25% at 50 ng · kg−1 · min−1) in SHR. Infusion of N G-nitro-l-arginine methyl ester (l-NAME) into the renal medulla unmasked ANG II sensitivity in WKY rats while l-arginine given into the renal medulla abolished the responses to ANG II in SHR. In 18- to 19-wk-old SHR treated with enalapril (25 mg · kg−1 · day−1 when 4 to 14 wk old), ANG II did not alter MBF significantly, but sensitivity to ANG II was unmasked after l-NAME was infused into the renal medulla. Endothelium-dependent vasodilation (assessed with aortic rings) was significantly greater in treated SHR when compared with that in control SHR. These results indicate that MBF in SHR is sensitive to low-dose ANG II and suggest that this effect may be due to an impaired counterregulatory effect of nitric oxide. Long-term treatment with enalapril improves endothelium-dependent vascular relaxation and decreases the sensitivity of MBF to ANG II. These effects may be causally related to the persistent antihypertensive action of enalapril in SHR.
Effect of repetitive icv injections of ANG II on c-Fos and AT1-receptor expression in the rat brain
Authors: Moellenhoff Eva , Blume Annegret , Culman Juraj , Chatterjee Bimal , Herdegen Thomas , Lebrun Christine J. , Unger Thomas
Published: December 2017

ANG II has been implicated in neuroplastic processes via stimulation of inducible transcription factors (ITF) in the brain. In the present study, we investigated the effects of acute vs. repetitive once daily intracerebroventricular injections of ANG II for 7 days on the expression of ITF and constitutive transcription factor (CTF) and the AT1 receptor in the median preoptic area (MnPO), the subfornical organ (SFO), and the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). After repetitive injections, the expression of c-Fos declined by ∼50% in MnPO, SFO, PVN, and SON compared with controls injected once. The desensitization of c-Fos occurred on the transcriptional level as shown in the SON by RT-PCR. Apart from a novel expression of c-Jun in the SON, the ITF c-Jun, JunB, JunD, and Krox-24 did not change after repetitive stimulation. Neither were the CTF, calcium response element binding protein, activating transcription factor 2, and serum response factor altered after repetitive vs. single injections of ANG II. The AT1 receptor was coexpressed with c-Fos/c-Jun. Immunohistochemical stainings suggest an increase in AT1-receptor number in MnPO, SFO, PVN, and SON on chronic stimulation compared with once-injected controls. These findings demonstrate that repetitive periventricular stimulation with ANG II essentially alters the expression of transcription factors compared with acute stimulation and suggest c-Fos and c-Jun as major intermediates of the AT1-receptor transcription.
Oxygen affinity and amino acid sequence of myoglobins from endothermic and ectothermic fish
Authors: Marcinek David J. , Bonaventura Joseph , Wittenberg Jonathan B. , Block Barbara A.
Published: December 2017

Myoglobin (Mb) buffers intracellular O2and facilitates diffusion of O2through the cell. These functions of Mb will be most effective when intracellular Po2is near the partial pressure of oxygen at which Mb is half saturated (P50) of the molecule. We test the hypothesis that Mb oxygen affinity has evolved such that it is conserved when adjusted for body temperature among closely related animals. We measure oxygen P50s tonometrically and oxygen dissociation rate constants with stopped flow and generate amino acid sequence from cDNA of Mbs from fish with different body temperatures. P50s for the endothermic bluefin tuna, skipjack tuna, and blue marlin at 20°C were 0.62 ± 0.02, 0.59 ± 0.01, 0.58 ± 0.04 mmHg, respectively, and were significantly lower than those for ectothermic bonito (1.03 ± 0.07 mmHg) and mackerel (1.39 ± 0.03 mmHg). Because the oxygen affinity of Mb decreases with increasing temperature, the above differences in oxygen affinity between endothermic and ectothermic fish are reduced when adjusted for the in vivo muscle temperature of the animal. Oxygen dissociation rate constants at 20°C for the endothermic species ranged from 34.1 to 49.3 s−1, whereas those for mackerel and bonito were 102 and 62 s−1, respectively. Correlated with the low oxygen affinity and fast dissociation kinetics of mackerel Mb is a substitution of alanine for proline that would likely result in a more flexible mackerel protein.
Parabrachial nucleus modulates cardiovascular responses to blood loss
Authors: Blair M. L. , Jaworski R. L. , Want A. , Piekut D. T.
Published: December 2017

The goal of this study was to determine the role of the pontine lateral parabrachial nucleus (LPBN) in the compensatory responses to blood loss. Conscious unrestrained rats with complete, partial, or sham bilateral ibotenic acid lesions of the LPBN were subjected to a hypotensive 16-ml/kg blood withdrawal via arterial catheter. Complete lesions (LPBNx) encompassed the entire LPBN and extended into the ventrolateral parabrachial region to encroach on the Kolliker-Fuse nucleus. Partial lesions were restricted to the body of the LPBN and spared the outer rim of the external lateral subnucleus of the LPBN. In all three groups, serum corticosterone concentration and plasma renin activity increased four- to fivefold after hemorrhage ( P < 0.01), and immunocytochemistry demonstrated numerous Fos-positive neurons in the hypothalamic supraoptic nucleus. However, the cardiovascular responses to hypotensive blood loss differed for complete and partial lesions. Blood pressure failed to recover in LPBNx rats and was significantly lower in LPBNx (66 ± 4 mmHg) than in rats with partial or sham lesions (98 ± 4 and 85 ± 5 mmHg, respectively) at 40 min posthemorrhage. In contrast, rats with partial lesions had a significant attenuation of the posthemorrhage bradycardia. This implies that a population of neurons within the body of the LPBN is essential for full expression of the bradycardia that accompanies hemorrhagic hypotension, whereas the ventrolateral parabrachial region is essential for normal restoration of arterial pressure after hypotensive hemorrhage.
Adaptation of intestinal production of apolipoprotein A-IV during chronic feeding of lipid
Authors: Kalogeris Theodore J. , Painter Richard G.
Published: December 2017

We examined the effect of daily fat supplementation on intestinal gene expression and protein synthesis and plasma levels of apolipoprotein A-IV (apo A-IV). Rats were fasted overnight and then given intragastric bolus infusion of either saline or fat emulsion after 0, 1, 2, 4, 8, or 16 days of similar daily feedings. Four hours after the final saline or fat infusion, plasma and jejunal mucosa were harvested; plasma levels of apo A-IV, triglycerides, and leptin were measured, as well as mucosal apo A-IV mRNA levels and biosynthesis of apo A-IV protein. In response to fat, plasma apo A-IV showed an initial 40% increase compared with saline-injected control rats; with continued daily fat feeding, the plasma A-IV response showed rapid and progressive diminution such that by 4 days, plasma A-IV was not different between fat- and saline-fed groups. Jejunal mucosal apo A-IV synthesis and mRNA levels also showed time-dependent refractoriness to fat feeding. However, the kinetics of this effect were considerably slower than in the case of plasma, requiring 16 days for completion. There was no correlation between plasma leptin or triglyceride levels and intestinal apo A-IV synthesis or plasma apo A-IV. These results indicate rapid, fat-induced, posttranslational adapation of plasma apo A-IV levels and a slower, but similarly complete pretranslational adaptation of intestinal apo A-IV production, which are independent of plasma levels of leptin.
Brain angiotensin receptors and sympathoadrenal regulation during insulin-induced hypoglycemia
Authors: Worck René H. , Staahltoft Dennis , Jonassen Thomas E. N. , Frandsen Erik , Ibsen Hans , Petersen Jørgen S.
Published: December 2017

Simultaneous blockade of systemic AT1 and AT2 receptors or converting enzyme inhibition (CEI) attenuates the hypoglycemia-induced reflex increase of epinephrine (Epi). To examine the role of brain AT1 and AT2 receptors in the reflex regulation of Epi release, we measured catecholamines, hemodynamics, and renin during insulin-induced hypoglycemia in conscious rats pretreated intracerebroventricularly with losartan, PD-123319, losartan and PD-123319, or vehicle. Epi and norepinephrine (NE) increased 60-and 3-fold, respectively. However, the gain of the reflex increase in plasma Epi (Δplasma Epi/Δplasma glucose) and the overall Epi and NE responses were similar in all groups. The ensuing blood pressure response was similar between groups, but the corresponding bradycardia was augmented after PD-123319 ( P < 0.05 vs. vehicle) or combined losartan and PD-123319 ( P < 0.01 vs. vehicle). The findings indicate 1) brain angiotensin receptors are not essential for the reflex regulation of Epi release during hypoglycemia and 2) the gain of baroreceptor-mediated bradycardia is increased by blockade of brain AT2 receptors in this model.
Ambient temperature modulates hypoxic-induced changes in rat body temperature and activity differentially
Authors: Bishop B. , Silva G. , Krasney J. , Nakano H. , Roberts A. , Farkas G. , Rifkin D. , Shucard D.
Published: December 2017

When rats, acclimated to an ambient temperature (Ta) of 29°C, are exposed to 10% O2 for 63 h, the circadian rhythms of body temperature (Tb) and level of activity (La) are abolished, Tb falls to a hypothermic nadir followed by a climb to a hyperthermic peak, Laremains depressed (Bishop B, Silva G, Krasney J, Salloum A, Roberts A, Nakano H, Shucard D, Rifkin D, and Farkas G. Am J Physiol Regulatory Integrative Comp Physiol 279: R1378–R1389, 2000), and overt brain pathology is detected (Krasney JA, Farkas G, Shucard DW, Salloum AC, Silva G, Roberts A, Rifkin D, Bishop B, and Rubio A. Soc Neurosci Abstr 25: 581, 1999). To determine the role of Ta in these hypoxic-induced responses, Tb and La data were detected by telemetry every 15 min for 48 h on air, followed by 63 h on 10% O2 from rats acclimated to 25 or 21°C. Magnitudes and rates of decline in Tb after onset of hypoxia were inversely proportional to Ta, whereas magnitudes and rates of Tb climb after the hypothermic nadir were directly proportional to Ta. No hyperthermia, so prominent at 29°C, occurred at 25 or 21°C. The hypoxic depression of La was least at 21°C and persisted throughout the hypoxia. In contrast, Ta was a strong determinant of the magnitudes and time courses of the initial fall and subsequent rise in Tb. We propose that the absence of hyperthermia at 21 and 25°C as well as a persisting hypothermia may protect the brain from overt pathology.