[Effect of peroxynitrite on the reactivity of rabbit pulmonary arteries in vitro]

To investigate the effect of peroxynitrite (ONOO(-)) on the reactivity of rabbit pulmonary artery, the responses of rabbit pulmonary artery rings (PARs) pre-incubated with ONOO(-) to endothelium-dependent and receptor-dependent relaxants ACh and ADP, endothelium-dependent and receptor-independent relaxant calcium ionophore A23187, endothelium-independent relaxant sodium nitroprusside (SNP) and alpha(1)-adrenoceptor agonist phenylephrine (PE) were observed in vitro in an accumulative manner. (1) Relaxations of PARs to ACh, calcium ionophore A23187 and ADP were markedly impaired with shift of accumulative dose-response curve of each agonist to the right. Inhibition of endothelium-dependent and receptor-dependent or independent relaxation by ONOO(-) was dose-dependent. (2) ONOO(-) incubation inhibited SNP-induced relaxation in a dose-dependent manner. (3) Contractile response of PARs to PE varied with the different doses of ONOO(-). In PARs pre-incubated with 0.5 mmol/L ONOO(-), contractile response was significantly enhanced with shift of PE accumulative dose-response curve to the left, whereas in PARs pre-incubated with 1.0 mmol/L or 2.0 mmol/L ONOO(-), it was markedly reduced with right shift of PE accumulative dose-response curve. (4) Vehicle of ONOO(-) had no effect on responses to each agonist.Decomposed ONOO(-) had minimal effect on the response to PE and ADP, in contrast, relaxation of PARs to ACh, A23187 and SNP were enhanced. These results indicate that ONOO(-) may contribute to regulatory disorder of pulmonary artery reactivity.