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

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

Research output: Contribution to journalArticleScientificpeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)871-7
Number of pages7
JournalJOURNAL OF CARDIOVASCULAR PHARMACOLOGY
Volume18
Issue number6
DOIs
Publication statusPublished - Dec 1991
Externally publishedYes
Publication typeA1 Journal article-refereed

Keywords

  • Animals
  • Cyclic GMP/metabolism
  • Guanosine/pharmacology
  • Guanosine Triphosphate/pharmacology
  • In Vitro Techniques
  • Male
  • Molsidomine/analogs & derivatives
  • Muscle, Smooth, Vascular/drug effects
  • Nitroglycerin/pharmacology
  • Rats
  • Rats, Inbred Strains
  • Sodium Nitrite/pharmacology
  • Vasodilation/drug effects

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