Endothelial mediated inhibition of contraction and increase in cyclic GMP levels evoked by the alpha-adrenoceptor agonist B-HT 920 in rat isolated aorta.

In the presence of endothelium maximal contractions of rat aorta preparations evoked by B-HT 920 were about 10% of those evoked in the absence of endothelium. 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)azepin dihydrochloride (B-HT 920, 0.1 microM to 0.1 mM) induced concentration-dependent contractions of rat aorta in the absence of endothelium. Maximal contractions were comparable in magnitude to those induced by noradrenaline. In the presence of endothelium but not in its absence B-HT 920 (0.1 mM) stimulated an increase in tissue cyclic GMP levels of about 2 fold. Levels of cyclic AMP were unaffected. Removal of endothelium reduced basal tissue levels of cyclic GMP. The guanylate cyclase inhibitor methylene blue (0.5 microM) potentiated B-HT 920-induced contractions in the presence of endothelium and inhibited increases in cyclic GMP. In the presence of endothelium 5,8,11,14-eicosatetraynoic acid (ETYA; 0.1 mM), an inhibitor of both lipoxygenase and cyclo-oxygenase systems, inhibited the B-HT 920-induced increase in cyclic GMP but did not potentiate B-HT 920-induced contractions. ETYA also antagonized B-HT 920-induced contractions in the absence of endothelium. It is concluded that endothelium continuously releases a product or products which influence the smooth muscle. Inhibition of B-HT 920-induced contractions in the presence of endothelium is associated with increased tissue levels of cyclic GMP.