Effects of atrial natriuretic factor, sodium nitroprusside, and acetylcholine on cyclic GMP levels and relaxation in rat aorta

Abstract

The purpose of this study was to investigate the mechanisms whereby an endothelium-dependent vasodilator, acetylcholine, a nitrovasodilator, sodium nitroprusside and atrial natriuretic factor (atriopeptin II), elevate cyclic GMP levels and induce relaxation in rat thoracic aorta. Methylene blue inhibited the elevated cyclic GMP levels and relaxation due to sodium nitroprusside and acetylcholine, but not those to atriopeptin II. Cyanide inhibited relaxations to all three vasodilators, but inhibited the elevated cyclic GMP levels in response to only nitroprusside and acetylcholine. The reducing agents sodium borohydride, dithiothreitol, sucrose and isoproterenol all inhibited the elevated cyclic GMP levels due to nitroprusside and acetylcholine, while the increased cyclic GMP levels with atriopeptin II were unaffected by sodium borohydride, sucrose and isoproterenol. The effects of the reducing agents on relaxation induced by the vasodilators were difficult to interpret due to their nonspecific contractile and relaxant properties. Agents and procedures known to inhibit the Na+, K+-pump and relaxation to endothelium-dependent vasodilators and nitroprusside, including ouabain, K+-free, Mg2+-free and low Na+ Krebs-Ringer bicarbonate solution, all partially inhibited relaxations to atriopeptin II. Relaxations to atriopeptin II were also inhibited in tissues contracted with KCl. The present results suggest that the mechanism of atrial natriuretic factor-induced increased cyclic GMP levels, in contrast to that of nitroprusside and acetylcholine, does not involve the formation of free radicals, a reducible species or interaction with heme. Furthermore, the cyclic GMP formed in response to nitroprusside, acetylcholine and atrial natriuretic factor mediates relaxation through a common mechanism that may be functionally antagonized by agents and procedures which result in membrane depolarization.