Endothelium-dependent relaxation in rat aorta may be mediated through cyclic GMP-dependent protein phosphorylation

Abstract

The action of some vascular smooth muscle relaxants depends on the presence of the endothelium^1–10. We have recently shown that relaxation may be mediated through the formation of cyclic GMP¹⁰. The nitrovasodilators are another class of relaxants which exert ,their effects through the formation of cyclic GMP^11–13, although their relaxation is independent of the presence of the endothelium^1,2,10. Their relaxant properties seem to depend on free radical formation—specifically, the formation of nitric oxide^14,15. The NO-induced smooth muscle relaxation is proposed to occur through activation of guanylate cyclase and the formation of cyclic GMP^11–13. Protein phosphorylation is thought to be a common event in the pathway for many biological phenomena¹⁶. Moreover, sodium nitroprusside and 8-bromo cyclic GMP induce similar patterns of protein phosphorylation in intact rat thoracic aorta¹⁷. Here we report that the patterns of protein phosphorylation induced by the endothelium-dependent vasodilators and nitrovasodilators were identical. Incorporation of ³²P into myosin light chain was decreased by both classes of agents. Removal of the endothelium abolished the changes in phosphorylation with the endothelium-dependent vasodilator (acetylcholine), but not those with the nitrovasodilator (sodium nitroprusside). These results suggest that endothelium-dependent vasodilators and nitrovasodilators induce relaxation through cyclic GMP-dependent protein phosphorylation and dephosphorylation of myosin light chain.