Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cromakalim (BRL 34915), a K+ channel activator, and diltiazem relaxed isolated rat aortic rings contracted with a low KCl concentration (25 mM). Gilbenclamide (0.1-3 microM) did not modify base-line resting tension or responses to KCl but prevented the vasorelaxant effects of cromakalim without affecting those of diltiazem or nitrendipine. Cromakalim, in contrast to the latter compounds, did not relax aortic rings contracted with 55 mM KCl. In pentobarbital-anesthetized rats prepared for hemodynamic measurements with Doppler flow probes, a 20-min i.v. infusion of cromakalim (5.0 micrograms/kg/min) lowered mean carotid artery blood pressure. This effect reached maximum after administration and was accompanied by decreases in systemic (35%), hindquarter (45%), mesenteric (27%), and renal (19%) vascular resistances. The blood pressure effects of cromakalim were not modified by BW 755C (lipo and cyclooxygenase inhibitor), idazoxan, methylatropine, methysergide, promethazine, propranolol, SCH 23390 (DA-1 receptor antagonist), S-sulpiride, RP 59227 (antagonist of platelet activating factor receptors) or by bilateral vagotomy associated with ligation of carotid arteries. However, in rats pretreated with the hypoglycemic sulfonylureas glibenclamide or glipizide (20 mg/kg i.v.), cromakalim, in contrast to diltiazem or dihydralazine, failed to produce hypotension. In rats deprived of sympathetic drive by pithing, cromakalim produced only a minor fall in blood pressure; however, this effect became pronounced when the low base-line blood pressure of this preparation was elevated by an i.v. infusion of vasopressin and could be prevented by glibenclamide. In conclusion, cromakalim posseses a novel mechanism of vasorelaxation that is consistent with the activation of a cellular outward K+ current.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasorelaxant effects of cromakalim in rats are mediated by glibenclamide-sensitive potassium channels. 249 53

1. The blood pressure lowering and anti-vasoconstrictor effects of BRL 34915 and nifedipine were compared in female spontaneously hypertensive rats (SHR). 2. In conscious SHR, intravenous injection of BRL 34915 (0.1, 0.3 mg kg-1) produced rapid, dose-related falls in mean arterial pressure of greater than 3 h duration. Nifedipine, at the same intravenous dose levels, also evoked rapid anti-hypertensive effects, though these responses were of lesser magnitude and duration than those observed for BRL 34915. 3. In anaesthetized, ganglion-blocked SHR, BRL 34915 (0.1, 0.3 mg kg-1 i.v.) dose-dependently antagonized the pressor responses to incremental intravenous infusions of noradrenaline (3.8-28.5 ng min-1) or phenylephrine (120-907 ng min-1) but did not inhibit pressor responses to incremental infusions of methoxamine (0.47-3.63 micrograms min-1), angiotensin II (7.0-52.9 ng min-1) or vasopressin (0.27-2.0 mu min-1). 4. In anaesthetized, ganglion-blocked SHR, nifedipine (0.1, 0.3 mgkg-1 i.v.) antagonized the pressor responses to each of the infused vasoconstrictor agents, being most effective against responses to noradrenaline or angiotensin II. 5. In pithed SHR, both BRL 34915 and nifedipine (each at 0.3 mg kg-1 i.v.) reduced the basal blood pressure level and produced marked inhibition of frequency-dependent pressor responses evoked by electrical stimulation of the spinal cord sympathetic outflow (0.25-4.0 Hz). Restoration of the basal diastolic blood pressure to within the control range, using a continuous intravenous infusion of vasopressin (0.98 mu min-1), prevented the inhibitory effect of BRL 34915. In the case of nifedipine, however, even raising the basal blood pressure to a level exceeding that recorded in control rats (with vasopressin, 2.0 mu min-1), did not reverse the inhibitory effect of the drug on frequency-dependent pressor responses. 6. It is concluded that the anti-hypertensive properties of BRL 34915 in SHR are probably unrelated to an anti-vasoconstrictor action. In contrast, it is suggested that the broadly-based anti-vasoconstrictor properties of nifedipine may contribute substantially to the anti-hypertensive properties of this drug.
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PMID:Studies on the anti-vasoconstrictor activity of BRL 34915 in spontaneously hypertensive rats; a comparison with nifedipine. 337 Mar 88

Isolated rat hindlimbs were perfused at 37 degrees C and constant physiological pressure (80 +/- 0.5 mmHg) while the flow rate that was allowed to freely self-adjust was monitored. Under these conditions, evidence was obtained for both alpha- and beta-adrenergic stimulation of oxygen consumption (VO2) in contrast to constant-flow perfusion, which has only convincingly shown alpha-adrenergic stimulation of VO2 in response to adrenergic agents. Addition of norepinephrine (NE; 1-33 nM) led to an increase in VO2 with a maximum of 29% above the basal value at 3.3 nM, even though the flow rate decreased. Phenylephrine (3.3-33 nM) and vasopressin (10-100 pM) also showed similar, but lesser in magnitude, vasoconstriction-associated stimulatory effects on VO2. Prazosin (an alpha 1-antagonist) completely reversed the NE-mediated decrease in flow rate and significantly blocked the increased VO2. In contrast, isoproterenol (10-1,000 nM) increased both flow rate (30%) and VO2 (32%). The isoproterenol-stimulated VO2 was not blocked by the beta 1-, beta 2-antagonist propranolol (10 microM), although the increased flow was reversed. In the presence of propranolol (1 or 10 microM), BRL-35135A (a beta 3-agonist) also stimulated VO2 (18%) without significant change in flow rate. These results lend further support to the role of the alpha 1-adrenoceptor in muscle VO2. In addition there is evidence for the presence of a functional beta 3-adrenoceptor as an additional subtype responsible for NE-mediated thermogenesis in the rat hindlimb.
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PMID:Constant-pressure perfusion of rat hindlimb shows alpha- and beta-adrenergic stimulation of oxygen consumption. 749 49

Clearance studies in rats using kappa opioid agonists have demonstrated that agonists that can cross the blood-brain barrier are more potent water diuretics than agonists which have limited access to the brain. The mechanism of kappa agonist-induced water diuresis is unclear but may involve inhibition of vasopressin secretion and/or an adrenomedullary factor. In the present study the effect of an alpha-2 adrenoceptor antagonist (yohimbine, 10 micrograms/kg.min i.v.) on kappa agonist-induced water diuresis was evaluated in conscious chronically instrumented rats. BRL 53117 (1-[(3,4-dichlorophenyl)acetyl]-2-[(3-hydroxy-1-pyrrolidinyl) methyl]4,4-dimethyl piperidine), a kappa agonist that can cross the blood-brain barrier, caused a dose-dependent (1-100 micrograms/kg) water diuresis which was attenuated by yohimbine. The effective dose to cause a free water clearnace of zero for BRL 53117 was 13 +/- 5 micrograms/kg in vehicle-treated rats and 37 +/- 12 micrograms/kg in yohimbine-treated rats. BRL 52974 (5-[(3,4-dichlorophenyl)acetyl]4-(1-pyrrolidinylmethyl)-4,5,6,7-te trahydro- 1H-imidazo[4,5-c]pyridine), a compound with limited ability to cross the blood-brain barrier, also caused a dose-dependent water diuresis, albeit at higher doses (30-3000 micrograms/kg), and thus a higher effective dose to cause a free water clearance of zero (129 +/- 61 micrograms/kg); however, the effect was abolished by yohimbine. The data suggest that kappa agonists cause a water diuresis by both a central mechanism involving inhibition of vasopressin secretion and a peripheral mechanism involving stimulation of renal alpha-2 receptors.
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PMID:Contribution of alpha-2 adrenoceptors to kappa opioid agonist-induced water diuresis in the rat. 803 21

Data suggest that kappa opioid agonist-induced water diuresis involves inhibition of vasopressin (AVP) secretion; however, it is not clear whether this action involves kappa receptors in the neurohypophysis or receptors behind the blood-brain barrier (BBB). We have investigated the site of action using three selective kappa agonists, BRL 52656 (S(-)-2-(1-pyrrolidinylmethyl)-1-(4-trifluoromethylphenyl) acetyl piperidine hydrochloride), BRL 53114 ((-)-1-(4-trifluoromethylphenyl) acetyl-2-(1-pyrrolidinymethyl)3,3- dimethyl piperidine hydrochloride) and BRL 52974 (4-(1-pyrrolidinylmethyl)5-(3,4-dichlorophenyl)acetyl-4,5,6,7-t etrahydroimidazo [4,5-c] pyridine), with varying abilities to cross the BBB. Chemical and functional assays indicate that BRL 52974 has limited ability to cross the BBB, whereas BRL 53114 and BRL 52656 can freely penetrate. BRL 52974 was significantly less potent than BRL 52656 and BRL 53114 in causing a water diuresis in conscious rats. The ED10S (i.v. doses to cause a positive free water clearance of 10 microliters/min.100 g) for BRL 52974, BRL 52656 and BRL 53114 were 181, 9 and 3.4 mg/kg, respectively. Furthermore, in dogs BRL 52656 and BRL 53114 but not BRL 52974 (30 micrograms/kg i.v.) were able to cause a significant water diuresis. The data demonstrate that opiate receptors behind the BBB are primarily involved in kappa agonist-induced water diuresis and possibly inhibition of AVP secretion.
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PMID:Opiate receptors within the blood-brain barrier mediate kappa agonist-induced water diuresis. 839 49

Glucocorticoids are known to regulate both the noradrenergic and GABAergic inputs to the paraventricular nucleus (PVN). However, little is known about the effects of glucocorticoids on the interaction of these two input systems. Here we examined the effects of bilateral adrenalectomy (ADX) on the noradrenergic modulation of GABAergic transmission in the type II PVN neurons labeled with a retrograde dye injected into the pituitary stalk. Noradrenaline either reduced or augmented the frequency of spontaneous inhibitory postsynaptic current (sIPSC) without changing the amplitude and decay time constant. These effects were blocked by alpha2A- and alpha(1A/1L)-adrenoceptor antagonists, respectively. ADX increased the proportion of the neurons showing the noradrenergic reduction and the extent of reduction in the IPSC frequency. The ADX-induced changes were reversed by supplementation of ADX rats with corticosterone (10-mg pellet). ADX also potentiated the noradrenergic reduction in the frequency of miniature IPSC and paired-pulse facilitation of evoked IPSC. BRL 44408 (3 microM), a alpha2A-adrenoceptor antagonist, blocked the noradrenergic reduction in ADX rats. Corticotropin-releasing hormone and/or vasopressin transcripts were detected in neurons displaying noradrenergic augmentation or reduction of IPSC frequency. ADX enhanced the proportion of neurons expressing corticotropin-releasing hormone. Collectively, the results suggest that depletion of corticosterone by ADX markedly potentiates the noradrenergic suppression of GABAergic transmission mediated by the alpha2A-adrenoceptors on the GABAergic terminals in the parvocellular neurosecretory PVN neurons. These results may provide a novel synaptic mechanism for the glucocorticoid-induced plasticity in the noradrenergic modulation of neuroendocrine function of the PVN.
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PMID:Adrenalectomy potentiates noradrenergic suppression of GABAergic transmission in parvocellular neurosecretory neurons of hypothalamic paraventricular nucleus. 1803 68