Endothelin-1 has a dilator effect on neonatal pig pulmonary vasculature.
Endothelin-1 (ET-1), a 21-residue potent vasoconstrictor peptide produced by endothelial cells, was reported to cause vasodilation in the systemic and pulmonary vascular beds. Therefore, in isolated perfused lungs from 7-day-old piglets, we studied the effects and the mechanisms responsible for the dilator effect of ET-1. ET-1 produced a mild transient decrease in perfusion pressure at low doses (less than 10(-7) M/g dry lung); at higher doses, a potent long-lasting vasoconstriction was noted. Indeed, the constrictor effect of ET-1 was at least equal to or greater than that of U-44069 and prostaglandin D2 (PGD2). When the vascular tone of the preparation was increased with U-46619, another stable endoperoxide analogue, the dilator response to low doses of ET-1 was increased, while the constrictor response remained unchanged. Indomethacin (2.8 x 10(-6) M) and glybenclamide (an ATP-sensitive potassium channel inhibitor) (10(-5) M) did not alter the responses to ET-1. The endothelium-derived relaxing factor (EDRF) inhibitor Nw-nitro-L-arginine (2 x 10(-4) M) not only inhibited the dilator response to ET-1 almost completely, but also potentiated the constrictor response. Finally, Nw-nitro-L-arginine alone had a mild vasoconstrictor effect in newborn pig lung. The results of these studies indicate that ET-1 has both vasodilator and vasoconstrictor activity in neonatal pig pulmonary vascular bed. This vasodilator activity may be mediated by EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)
Perreault
T
T
Department of Pediatrics, Montreal Children's Hospital, Quebec, Canada.
De Marte
J
J
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D019335:Nitroarginine; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D015230:Prostaglandin D2 / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D011450:Prostaglandin Endoperoxides, Synthetic; D019335:Nitroarginine; C028429:U 44069; D001120:Arginine; D015230:Prostaglandin D2; D005905:Glyburide; D007213:Indomethacin