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Peroxynitrite is a potent vasodilator agent in the pulmonary vascular bed of the rat
Author(s) -
Murthy Subramanyam N,
Uppu Rao M,
Casey David B,
Badejo Adeleke M,
Dhaliwal Jasdeep S,
Kadowitz Philip
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.620.1
Subject(s) - vasodilation , peroxynitrite , sodium nitroprusside , medicine , nitric oxide , pharmacology , soluble guanylyl cyclase , tachyphylaxis , hypoxia (environmental) , pulmonary hypertension , chemistry , superoxide , anesthesia , oxygen , guanylate cyclase , biochemistry , organic chemistry , enzyme
It has been reported that the vasodilator effects of peroxynitrite (PN) are tachyphylaxic; however, responses have not been determined in the pulmonary vascular bed of the rat. In the present study iv injections of PN (1, 3 and 10 mmol) decreased pulmonary and systemic arterial pressure. Responses to PN could be repeated without the development of tachyphylaxis. The decreases in pulmonary arterial (PA) pressure in response to PN were modest under baseline conditions but were greatly enhanced when baseline PA pressure was increased with U‐46619. Also, the iv injections of PN decreased PA pressure when baseline tone was increased by ventilatory hypoxia or administration of the eNOS inhibitor L‐NAME. Sodium nitroprusside and PN produced similar vasodilator responses in the pulmonary and systemic vascular beds. The repeated administration of PN did not alter responses to both vasoconstrictor and vasodilator agents, and did not impair endothelium dependent responses. The results of the present study show that PN has potent pulmonary vasodilator activity in the rat and is consistent with the hypothesis that PN is converted into a substance that has NO‐donor like activity and that the beneficial effects of PN may be derived in part from the inactivation of superoxide anion and the activation of soluble guanylate cyclase.