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.
Nossaman
B D
BD
Department of Anesthesiology, Tulane University Health Science Center, New Orleans, Louisiana 70112, USA.
Dabisch
P A
PA
Liles
J T
JT
Baber
S R
SR
Champion
H C
HC
Kaye
A D
AD
Feng
C-J
CJ
Anwar
M
M
Bivalacqua
T J
TJ
Santiago
J A
JA
De Witt
B J
BJ
Kadowitz
P J
PJ
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D009566:Nitrates / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D009566:Nitrates; D030421:Peroxynitrous Acid; C031618:sodium nitrate; D012977:Sodium Nitrite