DIFFERENTIAL RELEASE OF PROSTACYCLIN AND NITRIC-OXIDE EVOKED FROM PULMONARY AND SYSTEMIC VASCULAR BEDS OF THE PIG BY ENDOTHELIN-1

The vascular effects of endothelin-1 (ET-1) and the release of prostac yclin and nitric oxide (NO) evoked by this peptide were analyzed in an esthetized, mechanically ventilated pigs. ET-1 induced biphasic respon ses in both the pulmonary and systemic vascular beds characterized by a transient hypotension followed by a long-lasting hypertension. To ev aluate the involvement of prostacyclin and NO in the ET-1-dependent va scular response, we used indomethacin to block cyclooxygenase and N-G- nitro-L-arginine methyl ester (L-NAME) to block NO synthase. The resul ts show that the systemic hypotensive response to ET-1 is mediated by the release of prostanoids and NO, but these are not responsible for t he pulmonary hypotension. Indomethacin reduced the hypertensive effect of ET-1, showing that this peptide can also activate release of vasoc onstrictor cyclooxygenase metabolites. When L-NAME was administered af ter indomethacin, the pulmonary vasoconstrictor activity of ET-1 was c ounterbalanced by NO. By contrast, in pigs pretreated with indomethaci n plus L-NAME ET-1 caused transient systemic vasoconstriction, followe d by progressive reduction of vascular tone, probably because of relea se of vasodilator agents other than prostanoids or NO.