Peroxynitrite does not impair pulmonary and systemic vascular responses

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 ).