Ontogeny of Big endothelin-1 effects in newborn piglet pulmonary vasculature.
Endothelin-1 (ET-1), a 21-amino acid peptide produced by endothelial cells, results from the cleavage of preproendothelin, generating Big ET-1, which is then cleaved by the ET-converting enzyme (ECE) to form ET-1. Big ET-1, like ET-1, is released by endothelial cells. Big ET-1 is equipotent to ET-1 in vivo, whereas its vasoactive effects are less in vitro. It has been suggested that the effects of Big ET-1 depend on its conversion to ET-1. ET-1 has potent vasoactive effects in the newborn pig pulmonary circulation, however, the effects of Big ET-1 remain unknown. Therefore, we studied the effects of Big ET-1 in isolated perfused lungs from 1- and 7-day-old piglets using the ECE inhibitor, phosphoramidon, and the ETA receptor antagonist, BQ-123Na. The rate of conversion of Big ET-1 to ET-1 was measured using radioimmunoassay. ET-1 (10(-13) to 10(-8) M) produced an initial vasodilation, followed by a dose-dependent potent vasoconstriction (P < 0.001), which was equal at both ages. Big ET-1 (10(-11) to 10(-8) M) also produced a dose-dependent vasoconstriction (P < 0.001). The constrictor effects of Big ET-1 and ET-1 were similar in the 1-day-old, whereas in the 7-day-old, the constrictor effect of Big ET-1 was less than that of ET-1 (P < 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)
Liben
S
S
Department of Pediatrics, Montreal Children's Hospital, Quebec, Canada.
Stewart
D J
DJ
De Marte
J
J
Perreault
T
T
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011863:Radioimmunoassay; D013552:Swine
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D010456:Peptides, Cyclic; D011498:Protein Precursors; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon