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 prostacyclin and nitric oxide (NO) evoked by this peptide were analyzed in anesthetized, mechanically ventilated pigs. ET-1 induced biphasic responses in both the pulmonary and systemic vascular beds characterized by a transient hypotension followed by a long-lasting hypertension. To evaluate the involvement of prostacyclin and NO in the ET-1-dependent vascular response, we used indomethacin to block cyclooxygenase and NG-nitro-L-arginine methyl ester (L-NAME) to block NO synthase. The results show that the systemic hypotensive response to ET-1 is mediated by the release of prostanoids and NO, but these are not responsible for the pulmonary hypotension. Indomethacin reduced the hypertensive effect of ET-1, showing that this peptide can also activate release of vasoconstrictor cyclooxygenase metabolites. When L-NAME was administered after indomethacin, the pulmonary vasoconstrictor activity of ET-1 was counterbalanced by NO. By contrast, in pigs pretreated with indomethacin plus L-NAME ET-1 caused transient systemic vasoconstriction, followed by progressive reduction of vascular tone, probably because of release of vasodilator agents other than prostanoids or NO.
Clement
M G
MG
Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy.
Albertini
M
M
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D002245:Carbon Dioxide / Q000097:blood; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; D009569:Nitric Oxide; D011464:Epoprostenol; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin