Antagonists of EDRF attenuate acetylcholine-induced vasodilation in isolated hamster lungs

C. M. Tseng, W. Mitzner

Research output: Contribution to journalArticle

Abstract

To evaluate the role of endothelium-dependent relaxing factor (EDRF) in acetylcholine- (ACh) induced vasodilation in the intact pulmonary circulation, we examined the effects of atropine and three EDRF antagonists that have been shown to be effective in vitro: nitro-L-arginine (NOARG), hemoglobin (Hb), and methylene blue (MB). We studied ACh-induced dilation after preconstriction with angiotensin II and prostaglandin F(2α) (PGF(2α)) in hamster lungs perfused with Krebs solution containing Ficoll (4 g/dl) and indomethacin (10 μM). In the constricted lungs with no blockers, infusion of ACh (1 μM) decreased the constriction by 67%, and this effect was completely abolished by atropine pretreatment (1 μM). Treatment of hamster lungs with each of the three EDRF blockers, NOARG (30 μM), Hb (10 μM), and MB (250 μM), augmented the pressor responses to angiotensin II and PGF(2α). However, NOARG and MB inhibited the ACh-induced dilation by 49 and 60%, respectively, without affecting vasodilatory responses to isoproterenol, an agent that relaxes vascular smooth muscle independent of EDRF synthesis. In contrast, Hb significantly inhibited both ACh- and isoproterenol-induced vasodilations. Because all these EDRF antagonists attenuated ACh-induced vasodilation in intact hamster lungs, we conclude that EDRF plays a role in this response. Nonselective inhibitory effects of Hb in hamster lungs, however, suggest that mechanisms other than inhibition of EDRF by this agent are also involved.

Original languageEnglish (US)
Pages (from-to)2162-2167
Number of pages6
JournalJournal of applied physiology
Volume72
Issue number6
DOIs
StatePublished - 1992

Keywords

  • angiotensin II
  • hemoglobin
  • isoproterenol
  • methylene blue
  • nitro-L-arginine
  • prostaglandin F(2α)
  • pulmonary circulation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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