title: 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.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112-2699, USA.
authors.forename: Bobby D
authors.initials: BD
authors.lastname: Nossaman
authors.forename: Edward A
authors.initials: EA
authors.lastname: Pankey
authors.forename: Adeleke R
authors.initials: AR
authors.lastname: Badejo
authors.forename: David B
authors.initials: DB
authors.lastname: Casey
authors.forename: Satvika
authors.initials: S
authors.lastname: Uppu
authors.forename: Subramanyam N
authors.initials: SN
authors.lastname: Murthy
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003484:Cyanamide / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D012977:Sodium Nitrite / Q000494:pharmacology*; D013909:Thorax / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D003484:Cyanamide; D026422:S-Nitrosoglutathione; D005996:Nitroglycerin; D012977:Sodium Nitrite