Cyclic AMP mediates EDHF-type relaxations of rabbit jugular vein

Isolated rings of rabbit jugular vein have been used to test the hypothesis that formation of cAMP within the endothelial cell contributes to relaxati ons that are attributable to the endothelium-derived hyperpolarizing factor , EDHF. Relaxations induced by acetylcholine under conditions of combined N O synthase and cyclooxygenase blockade were almost abolished by inhibition of adenylate cyclase with the selective P-site agonist 2'-3'-dideoxyadenosi ne (2',3'-DDA). They were similarly attenuated by the gap junction inhibito rs 18 alpha-glycyrrhetinic acid (18 alpha-GA) and Gap 27 peptide which inte rrupt direct endothelium-smooth muscle communication without themselves aff ecting smooth muscle tone. By contrast, stimulation of adenylate cyclase wi th forskolin promoted gap junction-dependent relaxations, with concentratio n-relaxation curves to this agent exhibiting an equivalent rightward shift in the presence of 18 alpha-GA and following endothelial denudation. The fi ndings suggest that cAMP may cross from the endothelium to smooth muscle vi a gap junction channels and/or enhance the endothelial hyperpolarization no rmally associated with agonist stimulation. Both mechanisms may contribute to EDHF/gap junction-dependent relaxations, (C) 1999 Academic Press.