Hyperpolarization and relaxation of arterial smooth muscle caused by nitric oxide derived from the endothelium

Abstract

STIMULATION of the endothelial lining of arteries with acetyl-choline results in the release of a diffusible substance that relaxes and hyperpolarizes the underlying smooth muscle^1–9. Nitric oxide (NO) has been a candidate for this substance, termed endothelium-derived relaxing factor^10,11. But there are several observations that argue against the involvement of NO in acetylcholine-induced hyperpolarization. First, exogenous NO has no effect on the membrane potential of canine mesenteric arteries⁷. Second, although haemoglobin (believed to bind and inactivate NO (refs 11–15)) and methylene blue (which prevents the stimulation of guanylate cyclase^11–16) inhibit relaxation^7,12–14, neither has an effect on hyperpolarization^5,7,8. Finally, nitroprusside, thought to generate NO in vascular smooth muscle^14,16, relaxes rat aorta without increasing rubidium efflux¹⁷. Nevertheless, nitrovasodilators, nitroprusside and nitroglycerine cause hyperpolarization in some arteries^18–20. NO might therefore be responsible for at least part of the hyperpolarization induced by acetylcholine. We now report that hyperpolarization and relaxation evoked by acetylcholine are reduced by N^G-monomethyl-L-arginine, an inhibitor of NO biosynthesis from L-arginine^21–25. Thus NO derived from the endothelium can cause hyperpolarization of vascular smooth muscle, which might also contribute to relaxation by closing voltage-dependent calcium channels. Our findings raise the possibility that hyperpolarization might be a component of NO signal transduction in neurons or inflammatory cells.