Vasodilator actions of several N-nitroso compounds

Abstract

N-nitroso compounds can activate arterial guanylate cyclase and relax isolated arterial smooth muscle. The effects of these substances on the cardiovascular system in the anesthetized cat are unknown. The effects of several nitrosoguanidines and a nitrosamine, N-nitrosodimethylamine were compared, on arterial guanylate cyclase activity, isolated arterial smooth muscle tone and systemic vascular resistance in the anesthetized cat. Injections and infusions [i.v.] of the nitrosoguanidines glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) decreased systemic arterial pressure. During i.v. infusion of the nitrosoguanidines GTN and SNP, cardiac output was unchanged at the peak of the decrease in aortic pressure, indicating that the nitrosoguanidines GTN and SNP both reduced systemic vascular resistance. Intraarterial injections of the nitrosoguanidines produced dose-dependent decreases in perfusion pressure in the feline mesenteric vascular bed perfused at constant flow. These substances were potent relaxants of isolated arterial smooth muscle and markedly activated arterial guanylate cyclase. N-nitrosodimethylamine was devoid of vasodilator activity in vivo and exerted only minimal effects on isolated arterial smooth muscle tone or on arterial guanylate cyclase activity. A relationship between guanylate cyclase activation and arterial smooth muscle relaxation was demonstrated. The vasodilator effects on resistance vessels in vivo in response to selected N-nitroso compounds may involve such a mechanism. Although the significance of the presently reported cardiovascular responses to N-nitroso compounds is uncertain, N-nitroso compounds may represent a previously unrecognized class of substances which can be formed in the body and which possess marked vasodilator activity. This vasodilator activity may involve the relaxation of vascular smooth muscle though activation of guanylate cyclase.