Peroxynitrite does not impair pulmonary and systemic vascular responses

• Published in: Journal of applied physiology (1985) 2004-02, Vol.96 (2), p.455-462
• Main Authors: Nossaman, B. D, Dabisch, P. A, Liles, J. T, Baber, S. R, Champion, H. C, Kaye, A. D, Feng, C.-J, Anwar, M, Bivalacqua, T. J, Santiago, J. A, De Witt, B. J, Kadowitz, P. J
• Format: Article
• Language: English
• Subjects: Anesthesia; Animals; Biological and medical sciences; Blood Pressure - drug effects; Enzymes; Fundamental and applied biological sciences. Psychology; Hypoxia - physiopathology; Lungs; Male; Nitrates - pharmacology; Peroxynitrous Acid - pharmacology; Pulmonary Circulation - drug effects; Rats; Rats, Sprague-Dawley; Respiratory system; Sodium Nitrite - pharmacology; Vascular Resistance - drug effects; Vasoconstriction - drug effects; Vasodilation - drug effects
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01159.2002

Departments of Anesthesiology and Pharmacology, Tulane University Health Science Center, New Orleans, Louisiana 70112 Submitted 16 December 2002 ; accepted in final form 20 August 2003 The effects of peroxynitrite (ONOO - ) on vascular responses were investigated in the systemic and hindquarters vascular bed and in the isolated perfused rat lung. Intravenous injections of ONOO - decreased systemic arterial pressure, and injections of ONOO - into the hindquarters decreased perfusion pressure in a dose-related manner. Injections of ONOO - into the lung perfusion circuit increased pulmonary arterial perfusion pressure. Responses to ONOO - were rapid in onset, short in duration, and repeatable without exhibiting tachyphylaxis. Repeated injections of ONOO - did not alter systemic, hindquarters, or pulmonary responses to endothelium-dependent vasodilators or other vasoactive agonists and did not alter the hypoxic pulmonary vasoconstrictor response. Injections of sodium nitrate or nitrite or decomposed ONOO - had little effect on vascular pressures. Pulmonary and hindquarters responses to ONOO - were not altered by a cyclooxygenase inhibitor in a dose that attenuated responses to arachidonic acid. These results demonstrate that ONOO - has significant pulmonary vasoconstrictor, systemic vasodepressor, and vasodilator activity; that short-term repeated exposure does impair vascular responsiveness; and that responses to ONOO - are not dependent on cyclooxygenase product release. vasodilator responses; vasoconstrictor responses; oxidant; cyclooxygenase product; hypoxia Address for reprint requests and other correspondence: P. J. Kadowitz, Dept. of Pharmacology SL83, Tulane Univ. Medical Center, 1430 Tulane Ave., New Orleans, LA 70112 (E-mail: pkadowi{at}tulane.edu ).