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)

Myometrial tissue was obtained from non-pregnant women subjected to hysterectomy because of various gynaecological disorders, and from women undergoing caesarean section. Strip preparations were dissected and isometric tension was recorded. Nifedipine (2.9 X 10(-8)--2.9 X 10(-6)M) inhibited spontaneous contractile activity, mainly by reducing the amplitude of contraction in both non-pregnant and pregnant myometrium. The drug also inhibited potassium induced contractions in a concentration dependent manner. This effect seemed to be more pronounced in pregnant than in non-pregnant tissue. In preparations of pregnant human myometrium, normally polarized or potassium depolarized, oxytocin induced a contractile activity that was effectively inhibited by nifedipine. Nifedipine also relaxed contractions induced by vasopressin in isolated non-pregnant myometrium. It is concluded that the relaxant effect of nifedipine on isolated pregnant and non-pregnant human myometrium can be explained by inhibition of calcium influx. The results thus support the view, that calcium influx is an important step in the initiation of contractile activity in human uterine smooth muscle.
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PMID:Relaxant effects of nifedipine on isolated, human myometrium. 49 17

The effect of cholesterol enrichment on vascular smooth muscle cell (VSMC) calcium homeostasis was studied by evaluating calcium uptake, efflux, and intracellular content in cultured VSMC derived from the rat pulmonary artery. Incubation of VSMC with liposomes consisting of free cholesterol (FC) and phospholipid (2:1 molar ratio, 1 mg FC/ml medium) for 24 h resulted in a 69 +/- 19% increase (P less than 0.01; n = 10) in FC which was associated with a 73 +/- 11% increase (P less than 0.005; n = 10) in intracellular calcium content as assessed by isotopic equilibrium with 45Ca2+ and a 65 +/- 11% increase (P less than 0.024; n = 3) as assessed by atomic absorption spectroscopy. Cholesterol enrichment caused a marked increase in the unidirectional calcium uptake rate from 0.026 +/- 0.03 to 0.158 +/- 0.022 nmol calcium/s per mg protein (P less than 0.01; n = 3), but had no effect on calcium efflux. Nifedipine (1 microM) reduced (P less than 0.05; n = 6) the effect of cholesterol enrichment on unidirectional calcium uptake by 78 +/- 16%; and verapamil (10 microM), diltiazem (1 microM), and nifedipine (1 microM) each significantly inhibited the effect of cholesterol enrichment on intracellular calcium accumulation. Exposure of cholesterol-enriched VSMC to cholesterol-poor liposomes for 24 h returned both FC and calcium contents to control levels. Serum- and serotonin-stimulated calcium uptakes were potentiated 3.7- and 1.7-fold, respectively, in cholesterol-enriched VSMC, whereas endothelin, vasopressin, and thrombin-stimulated calcium uptakes were not affected. We conclude that VSMC FC content plays a role in regulating cellular calcium homeostasis, both under basal conditions and in response to selected agonists.
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PMID:Cholesterol enrichment increases basal and agonist-stimulated calcium influx in rat vascular smooth muscle cells. 175 51

Endothelin (ET) exerts various biological actions in mesangial cells, including stimulation of proliferation, contraction and phospholipase C activation. We investigated the presence of specific ET receptors on cultured rat mesangial cells, incubating the cells in the presence of [125I]ET-1 both at 22 and 4 degrees C. ET binding was time- and temperature-dependent and achieved equilibrium at 2 hr at 22 degrees C and at 5 hr at 4 degrees C. Scatchard analyses of equilibrium saturation curves with [125I]ET-1 and homologous competition curves revealed the presence of a single class of high-affinity binding sites (Kd = 31.4 +/- 7.08 pM). Heterologous competition experiments with ET-3 and sarafotoxin, however, indicated the presence of two binding sites for ET-related peptides in mesangial cells with a Kd for ET-3 of 41.5 +/- 19.2 and of 374 +/- 38.5 nM. Nifedipine and arginine-vasopressin failed to compete for ET binding sites. Preincubation of the cells with 1 nM ET-1 caused a dramatic decrease in ET binding capacity (from 0.5-0.02 fmol/100,000 cells) without affecting the Kd for the receptors (38 pM). ET receptor down regulation was not prevented by protein kinase C inhibition with H-7 and sangiovamycin, or after down regulation of protein kinase C induced by 24-hr preincubation with phorbol myristate acetate. ET receptor down regulation also exerts functional effects, as we found a decrease in intracellular-free calcium response to ET-1 after long-term preincubation with the same agonist. Our results are consistent with the presence of two binding sites for ET in rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelin binding and receptor down regulation in rat glomerular mesangial cells. 184 3

To determine whether calcium fluxes and angiotensin II influence osmoregulation of vasopressin (AVP) secretion, the effects of the calcium antagonist nifedipine and of the converting enzyme inhibitor enalapril on the AVP response to an osmotic load were compared to those of a placebo in seven normal female subjects. Plasma and urinary AVP were measured before and during a 3-h infusion of 2.5% hypertonic saline. Nifedipine (10 mg orally 2 h before and 10 mg at the start of the infusion) increased heart rate but did not change blood pressure. The changes in free water clearance and in urinary AVP induced by hypertonic saline under nifedipine were greater than in the control test, but the slope and the intercept of the regression line of plasma AVP upon plasma osmolality were not significantly different. Enalapril (10 mg 3 h before the infusion) did not change heart rate or blood pressure. Free water clearance and urinary AVP did not differ from the control test, but the slope of the regression line was less steep. These slight modifications of the response to an osmotic load suggest that calcium fluxes and angiotensin II only exert a limited influence on AVP osmoregulation in normal females.
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PMID:Influence of nifedipine and enalapril on osmoregulation of vasopressin. 243 81

The effect of antihypertensive drugs on receptor-dependent increase in Ca2+ basal level and its changes under stimulators action (thrombocytes activating factor, ADP and vasopressin) were studied by means of a fluorescent calcium probe "quin-2". Nifedipine blocked receptor-dependent increase of Ca2+ in thrombocytes in vitro as well as by oral administration, which was accompanied by decrease in vascular tone and BP. The degree of BP decrease correlated with that of depression of receptor-dependent increase of Ca2+ in thrombocytes. Combined therapy including nifedipine, propranolol and a diuretic resulted in more manifest inhibition of receptor-dependent calcium channels than monotherapy with nifedipine. Effect of antihypertensive drugs evidently depends on their influence on receptor-dependent Ca2+ cellular entrance.
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PMID:[Effect of hypotensive therapy on a receptor-dependent increase in Ca2+ in the thrombocytes of patients with hypertension]. 245 72

Changes in intracellular free Ca2+ concentration [( Ca2+]i) produced by growth factors and mitogens have been studied using aequorin-loaded Swiss 3T3 cells. Decreasing free Ca2+ in the external medium by using EGTA had no significant effect on the increase in [Ca2+]i produced by vasopressin, bradykinin, bombesin or prostaglandin E2, but reduced the increase in [Ca2+]i produced by platelet derived growth factor (PDGF) by 58%, by prostaglandin E1 44% and by prostaglandin F2 alpha 47%. The dihydropyridine Ca2+-channel antagonist nifedipine at 10 microM inhibited the [Ca2+]i response to PDGF by 41% in both the presence of and in the absence of external Ca2+. Methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate (BAY K8644), a Ca2+-channel agonist, at 10 microM produced an increase in [Ca2+]i and decreased the [Ca2+]i response to PDGF by 39%. Nifedipine did not block 45Ca2+ uptake or release by inositol 1,4,5-trisphosphate in saponin-permeabilized Swiss 3T3 fibroblasts but BAY K8644 inhibited 45Ca2+ release by inositol 1,4,5-trisphosphate. The results suggest that the increase in [Ca2+]i caused by PDGF in Swiss 3T3 fibroblasts is due to the influx of external Ca2+ through dihydropyridine sensitive Ca2+ channels, as well as release of internal Ca2+.
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PMID:Contribution of external and internal Ca2+ to changes in intracellular free Ca2+ produced by mitogens in Swiss 3T3 fibroblasts: the role of dihydropyridine sensitive Ca2+ channels. 247 47

Arginine8-vasopressin (AVP) causes hindlimb paralysis, loss of nociceptive responsiveness and increased arterial pressure after spinal subarachnoid injection in rats. In these experiments, the effects of paralytic intrathecal doses of AVP on rat brain and spinal cord blood flow, vascular resistance and cardiac output were measured using radiolabeled microspheres. Ten minutes after injection, AVP (10-100 pmol) elevated mean arterial pressures significantly, increased vascular resistances in thoracic and lumbosacral spinal cord and reduced blood flow to the lumbosacral spinal cord without altering cardiac output, total peripheral resistance and blood flow to brain and other spinal cord regions. Lumbosacral blood flows remained significantly reduced 30 min after injection of 100 pmol of AVP, and recovered to pretreatment base-line levels by 60 min postinjection. Lactic acid concentrations were elevated significantly in spinal cerebrospinal fluid samples removed 5 to 15 min after AVP injection (100 pmol). The selective AVP V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] arg8-vasopressin, which previously blocked the effects of AVP on hindlimb motor and nociceptive function, in these experiments also blocked the AVP-induced increases in arterial pressure and reductions in lumbosacral perfusion. Intravenous infusion of the vasodilators papaverine and nifedipine failed to block AVP-induced hindlimb paralysis. Nifedipine, however, did accelerate subsequent recovery of hindlimb motor function, although it did not alter the lumbosacral blood flow reductions measured at 10 and 30 min after AVP injection. These findings indicate that AVP has significant vascular effects in the rat spinal cord that are associated with ischemia and neurological dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arginine8-vasopressin reduces spinal cord blood flow after spinal subarachnoid injection in rats. 252 87

The interaction of the benzothiazolamine R 56865 with the nifedipine-sensitive component of the serotonin (5-HT)-, angiotensin II (AII)- and arginine-vasopressin (AVP)-induced contractions was studied in the isolated rat aorta. Nifedipine caused concentration-dependently (10(-9)-10(-6) mol/l) a slight rightward shift accompanied by a limited depression of the maximum of the concentration-response curves for 5-HT-, AII- and AVP-induced contractions. R 56865 (10(-5) mol/l) antagonized the contraction elicited by 5-HT and AII in a similar manner as nifedipine. The effect of R 56865 on 5-HT- and AII-induced contractions was no longer observed after pretreatment with nifedipine. The AVP-induced contraction was not affected by R 56865 (10(-5) mol/l). As shown previously, R 56865 is a weak inhibitor of potential-operated channels but inactive on Ca2+ channels activated by NA. In conclusion, R 56865 does not only differentiate between depolarization and receptor-stimulation, but also between the activation of Ca2+ channels by different types of receptors. We propose that R 56865 may interact with Ca2+ channels at a site which plays a role in their activation.
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PMID:R 56865 differentiates between contractile agents with respect to the nifedipine-sensitive component in the isolated rat aorta. 255 25

The vasoconstrictor responses induced by noradrenaline (NA), adrenaline (AD), serotonin (ST) and vasopressin (VP) on the anterior mesenteric artery of the rat and its branches, were maintained, although somewhat reduced when perfused with a Ca free solution that depletes extracellular Ca. The vasoconstrictor responses were abolished when Lanthanum, EDTA, Verapamil or Nifedipine were added to the Ca free solution. These drugs are known to displace plasmalemmal bound Ca that triggers vasoconstriction when the agonists attach to the receptors thus blocking the vasoconstrictor responses. When the mesenteric arteries were perfused with a Ca containing solution, to block the vasoconstriction induced by the agonists the concentration of La3+, EDTA, Verapamil and Nifedipine must be raised. Thus these drugs appear to compete with extracellular ionic Ca for the membranal sites involved in the activity of the agonists. K induced vasoconstriction was abolished when extracellular Ca was depleted by a Ca free solution and with lower concentrations of the anticalcic drug than those used to cancel the effect of the agonists. Ca appears to be attached to voltage operated channels less firmly than to receptor operated channels. NA, AD, ST and VP showed different sensitivity to the blocking effect of the various anticalcic drugs. This is probably explained by small differences in the structure of the Ca channels operated by the agonists.
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PMID:Organic and inorganic calcium blockers on voltage and receptor operated channels of resistance arteries of the rat. 257 39

Antianginal effects of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) in various experimental angina-pectoris models (anesthetized rats, spontaneously hypertensive rats (SHR] were compared with those of nifedipine, propranolol and hydralazine. Furthermore, the effects of these drugs on the pressure-rate product were evaluated. 1. Vasopressin test (SHR): The administration of KW-3049 at 10 micrograms/kg (i.v.) developed an inhibitory effect comparable to that of nifedipine at 200 micrograms/kg (i.v.) against the ischemic ECG changes caused by the intravenous administration of vasopressin at 1 U/kg. The effects of KW-3049 at 3 and 10 mg/kg (p.o.) lasted for 8 h or more. 2. Coronary occlusion test (rat): The rise of T-wave of epicardial ECG following ligation of coronary artery was inhibited by the administration of KW-3049 at doses of 30 and 100 micrograms/kg i.v. Nifedipine at dose of 200 micrograms/kg i.v. was slightly effective. 3. Isoproterenol (isoprenaline) test (rat): The fall of ST in ECG by the continuous infusion of isoprenaline (10 micrograms/kg/min) was almost completely prevented by propranolol (500 micrograms/kg i.v.). Also, KW-3049 (200 micrograms/kg i.v.) and nifedipine (200 micrograms/kg i.v.) significantly inhibited the decline of ST, in which the former was more effective than the latter. 4. Anoxia test (SHR): The fall of ST and rise of T-wave of ECG, induced by stopping artificial respiration of gallamine-immobilized SHR, were suppressed by the administration of KW-3049 at doses of 10 and 30 micrograms/kg i.v.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antianginal effects of the new calcium antagonist benidipine hydrochloride in anesthetized rats and spontaneously hypertensive rats. Electrocardiographic study. 321 44


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