Peroxynitrite does not impair pulmonary and systemic vascular responses

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.