Vasodilator actions of several N-nitroso compounds

Abstract

Recent studies have shown that N-nitroso compounds can activate arterial guanylate cyclase and relax isolated arterial smooth muscle; however, the effects of these substances on the cardiovascular system in the anesthetized cat are unknown. The present study was undertaken to compare the effects of several nitrosoguanidines and a nitrosamine, N-nitrosodimethylamine, on arterial guanylate cyclase activity, isolated arterial smooth muscle tone, and systemic vascular resistance in the anesthetized cat. Intravenous injections and infusions of the nitrosoguanidines glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) decreased systemic arterial pressure. During intravenous 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. In addition, 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. In contrast, 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. The present data demonstrate a relationship between guanylate cyclase activation and arterial smooth muscle relaxation and suggest that 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. It is possible that this vasodilator activity may involve the relaxation of vascular smooth muscle through activation of guanylate cyclase.

Biological activity of nitric oxide in the plasmatic compartment

“…These data require a reappraisal of current models of NO storage and transport in plasma, suggesting that other NO-derived species may contribute and that heme-NO reactions participate in plasmatic NO homeostasis and modulate reaction pathways. We suggest that these data support an expanded examination of the potential plasma NO storage species, including nitrite (21), N-nitrosamines (19,22,23), iron-nitrosyls (24), and recently identified nitrated lipids (25).…”

“…), it is now clear that, in addition to SNO-albumin, other reaction products form that may be capable of NO storage and delivery along the vasculature. These species may include nitrite (21), N-nitrosamines (19,22,23), iron-nitrosyls, (24) and recently identified nitrated lipids (25).In this study, we characterize, in vitro and in vivo, the reaction of physiological levels of NO (Ͻ2 M NO) with human plasma. We find that, in addition to SNO-albumin, nitrite and mercury-stable NO species form.…”

“…), it is now clear that, in addition to SNO-albumin, other reaction products form that may be capable of NO storage and delivery along the vasculature. These species may include nitrite (21), N-nitrosamines (19,22,23), iron-nitrosyls, (24) and recently identified nitrated lipids (25).…”

Nitrite Anion Provides Potent Cytoprotective and Antiapoptotic Effects as Adjunctive Therapy to Reperfusion for Acute Myocardial Infarction

“…37,38 Although NO per se is inactivated by reactions with hemoglobin, it may be stabilized in blood by the formation of NO-modified proteins, peptides, and lipids and oxidation to the anion nitrite. It is increasingly clear that a number of intravascular chemical NO-modified species are capable of mediating vasodilation, including S-nitrosothiols, 16,17 nitrite, 1,3,18,19 N-nitrosamines, [21][22][23][24] iron-nitrosyls, 25 and recently identified nitrated lipids. 26 -29 Both human blood flow experiments and studies of ischemia/reperfusion over the last 2 years suggest that nitrite is one of the major endocrine NO species in blood.…”

“…4 From a biochemical perspective, NO may be stabilized in blood by the formation of NO-modified proteins, peptides, and lipids, as well as by oxidation to the anion nitrite. Although these concepts remain controversial, it is likely that a number of intravascular species are capable of endocrine vasodilation, including S-nitrosothiols, 16,17 nitrite, 1,3,12-15,18 -20 N-nitrosamines, [21][22][23][24] iron-nitrosyls, 25 and the recently identified nitrated lipids. 26 -29 It has been suggested that the vasodilatory effects of nitrite are derived from the biochemical conversion to an S-nitrosothiol.…”