Effects of endothelin-1 in the isolated heart under ischemic and cardioplegic conditions.
We examined the effects of the vasoconstrictor peptide endothelin-1 in isolated hearts under ischemic and cardioplegic conditions. Isolated isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. Cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04-400 pmol in four groups of hearts. Coronary flow decreased with increasing dosages and was almost abolished at 400 pmol in control hearts perfused at a constant pressure of 100 mm Hg. In hearts made ischemic by reducing coronary perfusion pressure to 35 mm Hg, thus reducing coronary flow by 76%, the constrictor effect of endothelin-1 was well preserved. The endothelin-1 dose-response curve was unaltered when hearts were perfused with buffer containing 30 mM KCl to abolish mechanical activity without reducing extracellular Ca2+ concentration. A fourth group of hearts was perfused with Ca2(+)-free buffer, thus eliminating the source of extracellular Ca2+ as well as mechanical activity. In this group, the constrictor response to endothelin-1 was largely, but not completely, abolished, with a maximal constrictor effect of only 19% as opposed to 87% in control hearts. We conclude that in isolated rat heart endothelin-1 is a potent coronary constrictor under ischemic perfusion conditions and that absence of mechanical activity does not affect the action of endothelin-1, for which the presence of extracellular Ca2+ is essential. The small residual constrictor response with Ca2(+)-free perfusion is probably due to release of Ca2+ from intracellular stores.
Neubauer
S
S
Medizinische Universitätsklinik, Würzburg, F.R.G.
Ertl
G
G
Pulzer
F
F
Haas
U
U
Hirsch
A
A
Zimmermann
S
S
Kochsiek
K
K
D000818:Animals; D002118:Calcium / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects
D016232:Endothelins; D009569:Nitric Oxide; D002118:Calcium