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)

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

Small intramyometrial arteries and pieces of adjacent myometrial tissue were obtained from 25 non-pregnant women undergoing hysterectomy. Vascular and myometrial preparations were dissected, mounted in organ baths and isometric tension was recorded. Myometrial strips, but no vascular preparation, developed spontaneous contractile activity. Noradrenaline (NA) and vasopressin (VP) contracted both vessels and myometrium. Prostaglandin F2 alpha (PGF 2 alpha) contracted the myometrial tissue, but had only a minor effect on the vessels. Removal of extracellular calcium almost abolished the myometrial responses to high K+ (124 mM)-solution, PGF 2 alpha, NA and VP. The vascular responses remaining after this treatment were 18% (K+), 34% (NA) and 25% (VP) of control contractions induced by high K+ (124 mM). Nifedipine potently depressed myometrial contractions induced by NA and VP, but was less active against the vascular responses to these agents. In preparations exposed to calcium-free medium, nifedipine (10(-7) M) almost abolished myometrial contractions induced by calcium in the presence of K+ (124 mM), NA or VP. It also effectively depressed vascular responses to calcium in the presence of K+, but was less active if NA and VP were present. It is suggested that PGF2 alpha has almost no contractant effect on intramyometrial arteries, and that the activation process in these vessels is much less dependent on extracellular calcium than that of the myometrium.
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PMID:Differences in contractile activation between human myometrium and intramyometrial arteries. 386 53

Isolated urethral preparations from rabbit and man responded to transmural electrical stimulation with contraction when the basal tension was low, and with relaxation when the preparations were contracted by noradrenaline, clonidine, 5-hydroxytryptamine and lysine vasopressin. Both contractant and relaxant responses were abolished by tetrodotoxin, suggesting that they were caused by the action of transmitters released from nerves. The electrically induced contractions in the rabbit urethra had a threshold frequency of 5 to 6 Hz and maximum was reached at 40 Hz. The responses were markedly reduced by alpha-receptor blockers suggesting that the released contraction-mediating transmitter was mainly noradrenaline. The relaxant response was immediate and rapidly reversible. It was obtained at a threshold frequency of 1 to 2 Hz and maximum was reached at 10 to 15 Hz. It was not inhibited by propranolol, indomethacin, atropine or peptides such as substance P, VIP, vasopressin or somatostatin. Prostaglandin E2, isoprenaline, adenosine-5'-triphosphate and VIP relaxed the noradrenaline contracted rabbit urethra with a time course different from that of the electrically induced relaxation. Nifedipine and "calcium free" solution decreased the noradrenaline induced contraction but did not influence the relaxant response to electrical stimulation. It is suggested that the relaxant response of the isolated noradrenaline-contracted urethra to electrical stimulation is caused by an unknown transmitter released from nerves.
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PMID:Electrically induced relaxation of the noradrenaline contracted isolated urethra from rabbit and man. 613 Nov 47

The effect of nifedipine on the myocardial energy demand--supply imbalance caused by vasopressin-induced vasoconstriction, coronary occlusion, and their combined action was studied in isolated perfused rabbit hearts using the method of NADH fluorometry. Nifedipine (0.015 microgram/ml) completely prevented the development of NAD/NADH imbalance caused by coronary vasospasm. The role of vasoconstriction as an addition to coronary occlusion was very small in the development of regional energy imbalance and the vasopressin-induced detrimental effect was prevented by nifedipine. Energy imbalance caused by the occlusion alone was only partially improved by the drug. There was a delay in the development of energy imbalance and reduction in the final degree of NADH fluorescence response to the occlusion (97 +/- 8% vs. 66 +/- 9%, p less than 0.05).
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PMID:Effects of nifedipine on myocardial energy balance in experimental coronary vasoconstriction and occlusion. 617 85

In a double-blind versus placebo preliminary study conducted in seven mildly hypertensive patients, the 10-mg capsule form of nifedipine was able to reduce significantly systolic and diastolic blood pressure (-14%) for 3 h. In a single-dose, cross-over study, captopril (1 mg/kg) and nifedipine (20 mg) significantly reduced blood pressure in 12 patients with moderate essential hypertension, but the mean maximum arterial pressure reduction was faster and greater with nifedipine than with captopril (-23 +/- 2% at 37 +/- 15 min and -17 +/- 1% at 86 +/- 25 min, respectively). Nifedipine did not significantly alter the renin angiotensin aldosterone system in supine and upright positions, and the blood pressure drop it induced was not related to the initial level of activation of that system. Associated with the stimulation of the sympathetic nervous system, an increased release of vasopressin was noted during nifedipine administration. Finally, nifedipine, a calcium antagonist, was a potent antihypertensive drug through its vasodilating properties. It provoked specific hormonal alterations, i.e., stimulation of catecholamines and vasopressin release, whereas the renin angiotensin aldosterone system was not significantly altered.
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PMID:Acute antihypertensive and hormonal effects of a calcium antagonist in essential hypertension. 618 64

In a single-dose crossover study Captopril (SQ 14225), 1 mg/kg body weight, and Nifedipine (Bay a 1040) 20 mg were administered orally to 12 hospitalized patients with essential hypertension (Stage 1 or 2, W.H.O.). Both drugs significantly reduced blood pressure, but each dose acted differently: the mean maximum arterial pressure reduction was faster and greater with Nifedipine than with Captopril: -23 +/- 2% at 37 +/- 15 min and -17 +/- 1% at 86 +/- 25 min, respectively. Captopril inhibited angiotensin II and aldosterone production, but did not accelerate heart rate or stimulate vasopressin release. Nifedipine stimulated vasopressin release and increased heart rate, but the renin angiotensin aldosterone system was not significantly affected. The blood pressure reduction was related to the initial level of activation of the renin angiotensin system only for Captopril. The blood pressure reduction induced by one drug was not related to that produced by the other in the same patient.
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PMID:Antihypertensive and hormonal effects of single oral doses of captopril and nifedipine in essential hypertension. 702 55

The antianginal effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in various experimental angina models and compared with those of nifedipine and propranolol. In anesthetized dogs, YM-16151-4 (0.3 and 1 mg/kg intravenously, i.v.) increased coronary blood flow and reduced myocardial oxygen consumption (MVO2). In isolated dog coronary arteries, YM-16151-4 concentration-dependently inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 91 nM. In anesthetized rats, YM-16151-4 also inhibited the ST-segment depression induced by vasopressin (0.5 U/kg i.v.) with an ED50 value of 29 mg/kg orally, (p.o.). Nifedipine was also effective in these models, but propranolol was not. In addition, YM-16151-4 (0.3 mg/kg i.v.) inhibited the ST-segment elevation in the epicardial ECG induced by coronary artery occlusion in anesthetized dogs. Propranolol (1 mg/kg i.v.) also inhibited this elevation, but nifedipine (0.003 mg/kg i.v.) did not. In anesthetized dogs, furthermore, the prolongation of PQ-interval induced by YM-16151-4 was almost the same as that induced by propranolol. These results demonstrate that YM-16151-4, in contrast to nifedipine and propranolol, is fully effective in these various types of angina models. Thus, YM-16151-4 is expected to prove a valuable antianginal agent in treatment of various types of angina pectoris, with these antianginal effects resulting from the sum of its calcium entry blocking and beta 1-adrenoceptor blocking activities.
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PMID:Antianginal effects of YM-16151-4 in various experimental angina models. 768 38

Spontaneous and vasopressin-induced Ca2+ oscillations in cultured vascular smooth muscle (A7r5) cells were further examined and characterized. Intracellular Ca2+ concentrations ([Ca2+]i) were measured by use of a high-performance laser cytometer. When the oscillatory patterns in [Ca2+]i were analyzed with a power spectrum method, about 80% of cells exhibited spontaneous Ca2+ oscillations with the frequency of 0.02-0.5 Hz. Nifedipine abolished these repetitive spikes, whereas pinacidil partially attenuated their amplitude and frequency. When vasopressin (100 nM) was applied to A7r5 cells, there was an initial rise in [Ca2+]i, followed by a delayed sustained increase in [Ca2+]i. The one-pool, nonoscillatory model was employed to fit this biphasic change, and the difference between the observed response and the simulated response was then analyzed with a power spectral method. About 50% of cells were noted to display oscillatory patterns in [Ca2+]i after sustained increase in [Ca2+]i. The present study indicates that spontaneous Ca2+ oscillations in A7r5 cells are modulated by the activity of ATP-sensitive K+ channels and are not related to pertussis toxin-sensitive GTP-binding protein(s). On the basis of the one-pool, nonoscillatory model, it is suggested that the buffering capacity of internal stores appears to be stronger in the cells with spontaneous Ca2+ oscillations than in those in a quiescent state, and the vasopressin-mediated inhibition of accumulation by internal stores was attenuated when the cells exhibited spontaneous Ca2+ oscillations. The implementation of this minimum kinetic model integrated with a power spectrum method would be an alternative to understand the oscillating behavior in [Ca2+]i.
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PMID:Analytical studies of spontaneous and vasopressin-induced calcium oscillations in cultured vascular smooth muscle cells. 890 74

1. Vasoconstrictor effects of melatonin were examined in isolated rat tail arteries mounted either in an isometric myograph or as cannulated pressurized segments. Melatonin failed by itself to mediate observable responses but preactivation of the arteries with vasopressin (AVP) reliably uncovered vasoconstriction responses to melatonin with maxima about 50% of maximum contraction. Further experiments were conducted with AVP preactivation to 5-10% of the maximum contraction. 2. Responses to melatonin consisted of steady contractions with superimposed oscillations which were large and irregular in isometric but small in isobaric preparations. Nifedipine (0.3 microM) reduced the responses and abolished the oscillations. Charybdotoxin (30 nM) increased the magnitude of the oscillations with no change in the maximum response. 3. Forskolin (0.6 microM) pretreatment increased the responses to melatonin compared to control and sodium nitroprusside (1 microM) treated tissues. The AVP concentration required for preactivation was 10 fold higher than control in both the forskolin and nitroprusside treated groups. 4. In isometrically-mounted arteries treated with nifedipine, melatonin receptor agonists had the potency order 2-iodomelatonin > melatonin > S20098 > GR196429, and the MT2-selective antagonist luzindole antagonized the effects of melatonin with a low pK(B) of 6.1+/-0.1. 5. It is concluded that melatonin elicits contraction of the rat tail artery via an mt1 or mt1-like receptor that couples via inhibition of adenylate cyclase and opening of L-type calcium channels. Calcium channels and charybdotoxin-sensitive K channels may be recruited into the responses via myogenic activation rather than being coupled directly to the melatonin receptors. 6. It is proposed that the requirement of preactivation for overt vasoconstrictor responses to melatonin results from the low effector reserve of the melatonin receptors together with the tail artery having threshold inertia. Potentiative interactions between melatonin and other vasoconstrictor stimuli probably also result from the threshold inertia. A simple model is presented and a general framework for consideration of interactions between weak vasoconstrictor agonists and other vasoconstrictor stimuli is discussed.
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PMID:Mechanisms of melatonin-induced vasoconstriction in the rat tail artery: a paradigm of weak vasoconstriction. 1021 35

The purpose of this study was to clarify how eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, modulates the vascular action of vasopressin in rat aortic smooth muscle cell lines. The effects of EPA on Ca2+ mobilization and DNA synthesis elicited by vasopressin were investigated and compared to those of Ca2+ channel blocking agents, by means of Ca2+ measurements and the incorporation of [3H]thymidine. Patch-clamp techniques were also employed. Vasopressin (100 nM) elicited an initial peak of intracellular Ca2+ ([Ca2+]i), followed by a sustained phase due to Ca2+ entry. Nifedipine or nicardipine (1 microM), a potent L-type Ca2+ channel blocker, partly inhibited the sustained phase, but La3+ completely abolished it. EPA (10 microM) also inhibited it even in the presence of nicardipine. Under voltage-clamp conditions with CsCl-internal solution, depolarizing pulses positive to -30 mV from a holding potential of -40 mV elicited a slow inward current. The inward current was blocked by La3+, nicardipine, and nifedipine (1 microM), suggesting that the inward current mainly consisted of the voltage-dependent L-type Ca2+ channel (ICa.L). EPA (1-30 microM) also inhibited ICa.L in a concentration-dependent manner. The inhibitory effect of EPA was observed at concentrations higher than 1 microM, and its half-maximal inhibitory concentration (IC50) was 7.6 microM. Vasopressin induced a long-lasting inward current at a holding potential of -40 mV. The vasopressin-induced current was considered as a non-selective cation current (Icat) with a reversal potential of approximately +0 mV. Both nifedipine and nicardipine (10 microM) failed to inhibit it significantly, but La3+ completely abolished Icat. EPA also inhibited vasopressin-induced Icat in a concentration-dependent manner; its IC50 value was 5.9 microM. Vasopressin (100 nM) stimulated [3H]thymidine incorporation. Exclusion of extracellular Ca2+ with EGTA or La3+ markedly inhibited it. EPA (3-30 microM) also inhibited the incorporation induced by vasopressin, while nifedipine and nicardipine (1 microM) only partly inhibited it. These results suggested that EPA, unlike nifedipine and nicardipine, inhibited vasopressin-induced Ca2+-entry and proliferation in rat vascular smooth muscle cells, where the inhibitory effects of EPA on Icat as well as ICa.L might be involved. Thus, EPA would exert hypotensive and antiatherosclerotic effects.
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PMID:Eicosapentaenoic acid inhibits vasopressin-activated Ca2+ influx and cell proliferation in rat aortic smooth muscle cell lines. 1049 7


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