Mg. Clement et M. Albertini, DIFFERENTIAL RELEASE OF PROSTACYCLIN AND NITRIC-OXIDE EVOKED FROM PULMONARY AND SYSTEMIC VASCULAR BEDS OF THE PIG BY ENDOTHELIN-1, Prostaglandins, leukotrienes and essential fatty acids, 55(4), 1996, pp. 279-285
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.