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

The contribution of ATP-sensitive potassium channel (KATP channel) blockade in the vasoconstriction produced by vasopressin was studied. All experiments were performed using rat thoracic aorta cut in 4-mm rings, denuded from their endothelium and mounted into 20-ml organ baths. Glibenclamide (0.01-10 microM), a KATP channel antagonist, did not induce any measurable contraction, nor did it reduce the maximum contraction induced by vasopressin and phenylephrine. The specific inhibition of lemakalim-induced (a KATP channel activator) relaxation by vasopressin was investigated. Lemakalim (0.01-0.3 microM) relaxed both vasopressin (0.1 microM) and phenylephrine (0.3 microM) preconstricted vessels. However, in contrast to what would be expected from KATP blockade by vasopressin, rings preconstricted with vasopressin were more sensitive to the relaxant action of lemakalim, compared to phenylephrine preconstricted vessels (log[EC50] of -7.82 +/- 0.01 and -7.10 +/- 0.02, respectively, p < 0.05). Dose-response curves to papaverine (3-30 microM) in rings preconstricted with vasopressin and phenylephrine were comparable. When aortic rings were pretreated with lemakalim (0.1 microM), the maximum active tension induced by vasopressin was reduced (2.68 +/- 0.23 in control conditions vs. 0.62 +/- 0.08 g on pretreated vessels, p < 0.001), whereas that by phenylephrine was slightly increased. In order to explain the stronger relaxant action of lemakalim against vasopressin-induced constriction, the contribution of calcium influx through L-type calcium channels in the constriction of aortic rings to vasopressin and phenylephrine was compared.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:No role of ATP-sensitive potassium channels in the vasoconstriction produced by vasopressin. 773 60

The ATP-sensitive potassium channels (KATP) are activated either by a decrease in intracellular ATP content or by a lowering of the ATP-ADP ratio such as during stroke. We studied the role of cerebral KATP on arterial pressure during acute reduction of cerebral blood flow in 12-week-old male Wistar rats anesthetized with urethane by recording arterial pressure and heart rate continuously. After bilateral ligation of the common carotid arteries, glibenclamide, a specific blocker of KATP, was injected intracerebroventricularly into the cerebral lateral ventricle. Glibenclamide elicited a sustained vasopressor response in a dose-dependent manner in rats with bilateral carotid artery ligation (10 nmol, +15 +/- 2 mm Hg; 1 nmol, +5 +/- 1 mm Hg, P < .01 versus vehicle), but hemodynamic alterations were barely recorded with glibenclamide in sham-operated control rats. The abdominal sympathetic discharge was not increased significantly enough to explain the pressor mechanism. Similarly, pretreatments with intravenous injections of bunazosin, an alpha 1-adrenoceptor antagonist, did not affect the pressor response of intracerebroventricular glibenclamide. To investigate the vasopressor mechanism further, we measured plasma and pituitary concentrations of arginine vasopressin and determined the effects of vasopressin receptor antagonists. The intracerebroventricular injections of glibenclamide significantly increased the plasma concentration of vasopressin (P < .05) and significantly decreased the pituitary concentration of vasopressin (P < .05) in rats with bilateral carotid artery ligation. Intravenous pretreatment with the vasopressin V1 receptor antagonist OPC-21268 abolished the vasopressor response to intracerebroventricular glibenclamide (+16 +/- 2 versus +1 +/- 1 mm Hg, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cerebral ATP-sensitive potassium channels during acute reduction of carotid blood flow. 773 18

1. The effects of cirrhosis on mesenteric vascular reactivity were assessed in constantly perfused mesenteric arterial beds isolated from cirrhotic rats (carbon tetrachloride with phenobarbitone, n = 6), and from phenobarbitone-treated and untreated age-matched controls (n = 4,5). 2. At a constant flow rate of 5 ml min-1 there was no difference in basal perfusion pressure between the groups. Electrical field stimulation (EFS; 4-32 Hz, 90V, 1 ms, 30 s) of perivascular nerves caused frequency-dependent increases in perfusion pressure which were not different between the groups. Dose-dependent vasoconstrictor responses to exogenous noradrenaline (NA), methoxamine (an alpha 1-adrenoceptor agonist), adenosine 5'-triphosphate (ATP) and vasopressin were also similar between the groups. 3. The nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 30 microM) augmented constrictor responses to NA, EFS, methoxamine and vasopressin in all groups, and as shown for EFS and NA, this was reversed by L-arginine (300 microM). However, the maximum constrictor responses of cirrhotic preparations in the presence of L-NAME were significantly lower than those of both groups of control animals at the highest frequency of EFS (32 Hz) and highest doses of NA (0.15 and 0.5 mumol) and, compared to phenobarbitone-treated controls, methoxamine (5 mumol). Responses to ATP were significantly augmented by L-NAME only in the cirrhotic group. 4. A step-wise increase in perfusate flow to 10, 15 and 20 ml min-1 produced a broadly similar increase in perfusion pressure within each group. At increased flow rates, cirrhotic preparations were hyporesponsive to NA (15 nmol) compared to the phenobarbitone-treated animals but not the untreated controls. Glibenclamide (5 microM) or L-NAME (30 microM) had no significant effect on the relationship between flow and perfusion pressure or on responses to NA at the different flow rates. 5. We conclude that sympathetic neurotransmission is unchanged in cirrhosis. Endogenous NO is important in modulation of constriction in both normal and cirrhotic states. Changes in NO may occur in cirrhosis, although the role of this in hyporesponsiveness of cirrhotic preparations to NA at higher flow rates and to the greater potentiation of ATP-mediated constriction in the presence of L-NAME, together with the impact of factors such as changes in calcium and potassium channels, is not entirely clear.
 ...
PMID:Vasoconstrictor responsiveness of the rat mesenteric arterial bed in cirrhosis. 873 49

The amiloride-sensitive epithelial sodium channel (ENaC) contributes to the regulation of the sodium balance and blood pressure because it mediates a rate-limiting step in sodium transport across the epithelium of the distal nephron. The activity of ENaC is regulated by hormones, such as aldosterone and vasopressin, and by other intracellular or extracellular factors, but the mechanisms of these regulations are not yet well understood. It has been proposed that ENaC may be regulated by an associated ATP-binding cassette protein such as the cystic fibrosis conductance regulator or the K channel-associated sulfonylurea receptor. Glibenclamide, a known inhibitor of sulfonylurea receptor and cystic fibrosis conductance regulator, induced a dose-dependent and reversible stimulation (of the order of 40-50%) of the amiloride-sensitive current in oocytes expressing Xenopus ENaC, with a K1/2 of 45 +/- 5 microM. A similar effect was observed in oocytes expressing human ENaC, but not rat ENaC. Measurements performed with various combinations of rat and Xenopus subunits indicated that several subunits are involved in this effect. Glibenclamide also increased the transepithelial Na transport by the A6 Xenopus kidney cell line. Single-channel current recordings showed a doubling of the number of the open channels when glibenclamide was applied locally to the extracellular surface of the cell membrane. These results support the hypothesis of the existence of an associated ATP-binding cassette-type regulatory protein associated with the epithelial sodium channel.
 ...
PMID:Stimulation of epithelial sodium channel activity by the sulfonylurea glibenclamide. 1038 97

1. The effect of sulphonylurea drugs on hydrosmotic flow across toad urinary bladder epithelium was re-evaluated in the present study. Glibenclamide, added to the basolateral medium, significantly enhanced the osmotic flow induced by low doses of antidiuretic hormone (ADH) or forskolin (FK), while it inhibited the effect of exogenous cyclic adenosine monophosphate (cAMP) or its non-hydrolysable bromo derivative, 8-Br-cAMP, added to the basolateral medium. These opposite effects of glibenclamide on the transepithelial osmotic flow can be explained by a reduction of cAMP permeability across the basolateral membrane of the epithelium. The decrease in cAMP permeability leads, according to the direction of the cAMP gradient, to firstly an enhanced osmotic flow when cAMP is generated intracellularly by addition of ADH and FK, glibenclamide reducing cAMP exit from the cell, and secondly a decreased osmotic flow in response to cAMP (and 8-Br-cAMP) added to the basolateral medium, glibenclamide inhibiting, in this case, their entry into the cell. 2. The demonstration that glibenclamide actually inhibits the basolateral cAMP permeability rests on the fact that firstly it decreases the release of cAMP into the basolateral medium by about 40 %, at each concentration of ADH or forskolin tested, secondly it increases the cAMP content of paired hemibladders incubated in the presence of ADH or FK, when intracellular degradation was prevented by phosphodiesterase inhibition, and thirdly it decreases also the uptake of basolateral 8-Br-[3H]cAMP into paired toad hemibladders. 3. Taken together, the present data demonstrate that glibenclamide inhibits the toad urinary bladder basolateral membrane permeability to cAMP, most probably by a direct interaction with a membrane protein not yet indentified but distinct from the sulphonylurea receptor.
 ...
PMID:Inhibition of basolateral cAMP permeability in the toad urinary bladder. 1101 17

Nitric oxide (NO) is known to be an important relaxant of contractile activity in various muscles including the human uterine arteries. It has been suggested that NO plays a role in modulation of vascular action of arginin vasopressin (AVP), a strong vasoconstrictor of the human uterine arteries. Therefore, the purposes of this study were to investigate an involvement of endogenous NO in regulation of responses of the human intrauterine arteries to AVP and examine the effect of exogenous NO on contractions of the human intrauterine arteries evoked by AVP. Pretreatment of the artery rings with L-NA, an inhibitor of NO synthase significantly increased the resting force and enhanced the artery responses to AVP. The opposite effect has been observed after administration of 10(-6) mol/L sodium nitroprusside (SNP). Pretreatment of the artery rings with 10(-7) M CTX, a blocker of Ca(2+)-sensitive potassium channels with large conductance, did not change significantly their responses to AVP. Glibenclamide (1.5.10(-6) mol/L), a blocker of ATP-dependent potassium channels and apamin (10(-8) M), a specific blocker of Ca(2+)-sensitive potassium channels with small conductance strongly enhanced the maximum responses of the artery rings to AVP. Pretreatment with CTX significantly decreased the relaxation induced by SNP while apamin attenuated the sensitivity to SNP resulted in rightward shift of the concentration-response curve to SNP. In conclusion, this study indicates that: NO plays a role in regulation of both the vascular tone of the human intramyometrial arteries and their response to AVP. Ca(2+)-sensitive K(+) channels with small and large conductance are involved in the SNP-induced relaxation of these arteries. The pathways of this relaxation cannot be sufficiently explained at this moment and need further investigation.
 ...
PMID:Effect of nitric oxide on responses of the human uterine arteries to vasopressin. 1799 97