Vascular relaxation and cGMP in hypertension

Abstract

Isolated aortas from hypertensive rats have a decreased relaxation response to acetylcholine chloride (ACh), the calcium ionophore A23187, and sodium nitroprusside (SNP). Since the vascular relaxation responses to these vasodilators may be a result of increases in guanosine 3',5'-cyclic monophosphate (cGMP), we measured the cGMP response to these agents in isolated aortas from normotensive rats and rats with either mineralocorticoid-induced hypertension (DOCA), renovascular hypertension (1K1C), or coarctation-induced hypertension (Coarc). The aortas from the hypertensive rats had decreased basal levels of cGMP and attenuated increases in cGMP in response to ACh and A23187. Rises in cGMP in response to SNP were also attenuated in aortas from the hypertensive rats, even at concentrations that induced maximum relaxation of blood vessels from normotensive and hypertensive rats. The relaxation responses to atrial natriuretic factor (ANF) and the cGMP generated in isolated aortas by ANF were attenuated in hypertension. Removal of the endothelium markedly attenuated cGMP generation in response to ANF in vessels from normotensive and Coarc rats, but the relaxation responses to ANF were unaltered in vessels after the removal of the endothelium. The reversal of experimentally induced hypertension was associated with increases in cGMP levels following exposure of the isolated vessels to ACh. Also, vessels treated with methylene blue relaxed in response to SNP despite inhibition of cGMP accumulation. The decreased relaxation response to endothelium-dependent vasodilators is accompanied by decreases in cGMP accumulation; the decreased vascular cGMP content in response to endothelium-dependent vasodilators is not due to increases in phosphodiesterase activity of vascular smooth muscle; and SNP may relax blood vessels through “cGMP-dependent” and “cGMP-independent” mechanisms.