Analysis of responses to glyceryl trinitrate and sodium nitrite in the intact chest rat

Abstract

Responses to glyceryl trinitrate/nitroglycerin (GTN), S-nitrosoglutathione (GSNO), and sodium nitrite were compared in the intact chest rat. The iv injections of GTN, sodium nitrite, and GSNO produced dose-dependent decreases in pulmonary and systemic arterial pressures. In as much as cardiac output was not reduced, the decreases in pulmonary and systemic arterial pressures indicate that GTN, sodium nitrite, and GSNO have significant vasodilator activity in the pulmonary and systemic vascular beds in the rat. Responses to GTN were attenuated by cyanamide, but not allopurinol, whereas responses to nitrite formed by the metabolism of GTN were attenuated by allopurinol and cyanamide. The results with allopurinol and cyanamide suggest that only mitochondrial aldehyde dehydrogenase is involved in the bioactivation of GTN, sodium nitrite, and GSNO, whereas both pathways are involved in the bioactivation of nitrite anion in the intact rat. The comparison of vasodilator activity indicates that GSNO and GTN are more than 1000 fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures in the rat. Following administration of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), responses to GTN were significantly attenuated, indicating that responses are mediated by the activation of soluble guanylyl cyclase. These data suggest that the reduction of nitrite to nitric oxide formed from the metabolism of GTN, cannot account for the vasodilator activity of GTN in the intact rat and that another mechanism; perhaps the formation of an S-NO, may mediate the vasodilator response to GTN in this species.

Postprandial lipids accelerate and redirect nitric oxide consumption in plasma

“…Side-by-side comparisons available from the literature show that in normoxia the vasodilating potencies of SNO are markedly greater than that of nitrite [42; 43; 44; 45; 46; 47]. Thus, the extent to which hydrophobic phases in the vascular lumen might alter the vasoactivity of NO and contribute to endothelial dysfunction in vivo should be explored in future studies.…”

“…Although nitrate is of physiological relevance via its conversion to nitrite by commensal bacteria in the mouth, it is inert in mammalian cells [38] and thus the bioactivity of NO is lost upon conversion to nitrate. In contrast, both nitrite [39; 40; 41] and especially SNO [42; 43; 44; 45; 46; 47] are potent vasodilators. Yet, despite much interest in their bioactivity (see review by Lundberg and Weitzberg, 2010 [38]), relatively little is known about how these NO metabolites are produced in plasma.…”

Nitrite and Nitrate: From Bench to Bedside

“…Data was presented showing that nitrate consumption augments vascular compliance but did not alter flow-mediated vasodilation in healthy subjects [10]. Presentations also discussed biochemical and physiological similarities and differences between various organic versus inorganic nitrates and nitrites as it is now clear that these compounds are metabolized in diverse ways and can elicit different biological responses that could be harnessed for various therapeutic uses [11; 12]. …”