Effect of peroxynitrite on reactivity of rabbit pulmonary artery in vitro / 中国病理生理杂志

ABSTRACT

In order to investigate the possible role of ONOO- in regulatory disorder of pulmonary arterial tension in endotoxic shock, the responses of rabbit pulmonary arterial rings (PARs) preincubated with ONOO- to endothelial dependent and receptor dependent relaxants acetylcholine (ACh) and adenosine diphosphate (ADP), endothelial dependent and receptor independent relaxant A23187, endothelial independent relaxant sodium nitroprusside (SNP) and α1-adrenoceptor agonist phenylephrine (PE) were observed in vitro in accumulative manner. Results were as follow (1) Relaxations of PARs to ACh, A23187 and ADP were markedly impaired with shift of accumulative dose response curve of each agonist to the right. Inhibition of endothelial dependent and receptor dependent or independent relaxation by ONOO- was dose dependent. (2) ONOO- incubation inhibited SNP-induced relaxation in a dose dependent manner. Accumulative dose response curve of SNP was right shift to some degree depending on the doses of ONOO-. (3) Contractile response of PARs to PE varied with the different doses of ONOO-. In PARs preincubated with 0.5 mmol/L ONOO-, contractile reponse was significantly enhanced with shift of PE accumulative dose response curve to the left, while in PARs preincubated 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 every agonist, whereas 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 suggested that direct effect of ONOO- on pulmonary artery may be a key factor contributing to regulatory disorder of pulmonary arterial tension induced by LPS and pulmonary hypertension in the early stage of endotoxic shock.