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

The action of some vascular smooth muscle relaxants depends on the presence of the endothelium1–10. 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 GMP11–13, although their relaxation is independent of the presence of the endothelium1,2,10. Their relaxant properties seem to depend on free radical formation—specifically, the formation of nitric oxide14,15. The NO-induced smooth muscle relaxation is proposed to occur through activation of guanylate cyclase and the formation of cyclic GMP11–13. 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.