Modification of nitrovasodilator effects on vascular smooth muscle by exogenous GTP and guanosine.

Abstract:

:The effects of exogenous guanosine 5'-triphosphate (GTP) and guanosine on nitroglycerin-, sodium nitrite- and SIN-1-induced guanosine 3',5'-cyclic monophosphate (cyclic GMP) accumulation and smooth muscle relaxation were studied using endothelium-denuded rat mesenteric artery rings precontracted with noradrenaline. Preincubation of contracted artery rings with GTP (100 microM) or guanosine (100 microM) before eliciting relaxations with nitrovasodilators significantly shifted the dose-response curves of nitrocompounds to the left and augmented the increases in cyclic GMP. GTP and guanosine alone also induced cyclic GMP accumulation in pre-contracted artery rings. These effects of GTP and guanosine on nitrovasodilator responses were not related to the preincubation period (0-30 min). The present results raise the possibility of a cell membrane site of action for GTP and guanosine, which mediates the activation of soluble guanylate cyclase and leads to increased nitrovasodilator-induced cyclic GMP accumulation and arterial smooth muscle relaxation.

journal_name

J Cardiovasc Pharmacol

authors

Vuorinen P,Pörsti I,Metsä-Ketelä T,Manninen V,Vapaatalo H,Laustiola KE

doi

10.1097/00005344-199112000-00013

subject

Has Abstract

pub_date

1991-12-01 00:00:00

pages

871-7

issue

6

eissn

0160-2446

issn

1533-4023

journal_volume

18

pub_type

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