Peroxynitrite, a product of superoxide and nitric oxide, produces coronary vasorelaxation in dogs.
The vascular effect of peroxynitrite (ONOO-), a product of superoxide anion and nitric oxide, in isolated canine coronary arteries bathed in a 10 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid-buffered physiological salt solution (pH 7.4) was investigated. ONOO- was synthesized from nitrite and H2O2 in a quenched-flow reactor. Addition of 0.01 to 30 microM ONOO- produced a rapid, dose-dependent relaxation in all 17 rings of coronary arteries with a threshold concentration of 0.1 microM, IC50 of 1.0 +/- 0.1 microM and Emax of -96 +/- 0.5% (Means +/- S.E.M.). Incubation of arteries in a standard bicarbonate-buffered Krebs-Henseleit solution decreased slightly the sensitivity of ONOO- relaxation but did not alter the maximum effect (Emax = -97 +/- 1.1, n = 6 vessels). The ONOO(-)-induced coronary relaxation was reversible upon washing, and was also reproducible with repeated testings in the same ring. Mechanical removal of intimal endothelium did not alter the observed relaxant effect. Addition of superoxide dismutase (100 U/ml) potentiated the ONOO- relaxation by shifting the dose-response curve to the left (IC50 = 0.4 +/- 0.1 microM, P < .05, n = 17), whereas 3 microM hemoglobin inhibited it by shifting the curve to the right (IC50 = 20 +/- 4 microM, P < .05, n = 15). Relaxation was also observed with higher concentrations of sodium nitrite and decomposed ONOO-, although the time course of the development of these relaxations was considerably slower and with reduced sensitivity. In addition, superoxide dismutase had no effect on the latter relaxation responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Liu
S
S
Department of Pharmacology, University of Alabama at Birmingham.
Beckman
J S
JS
Ku
D D
DD
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D004285:Dogs; D005453:Fluorescence; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D012977:Sodium Nitrite / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
D009566:Nitrates; D014665:Vasodilator Agents; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; D012977:Sodium Nitrite