Effects of nisoldipine upon vasoconstrictor responses and binding of endothelin-1 in ischemic and reperfused rat hearts.
Changes in the vascular response of isolated, perfused rat hearts to endothelin-1 (ET-1) and binding of [125I]ET-1 to cardiac membranes were examined following ischemia (30 min, zero flow) and reperfusion (15 min). Infusion of ET-1 (0, 2.5, 5, 7.5, and 10 x 10(-10) M) increased the control heart perfusion pressure (61, 73, 88, 102, and 117 mm Hg, respectively). Ischemic and reperfused hearts were more sensitive to ET-1 infusion (p less than 0.05 at all concentrations). Nisoldipine (NIS, 1 nM) prevented the rise in sensitivity to ET-1 following ischemia and reperfusion. Two binding sites for [125I]ET-1 were identified in cardiac membranes. High-affinity (Kd = 0.04 nM, Bmax = 0.46 pmol/mg of protein) and low-affinity (Kd = 13.8 nM, Bmax = 5.4 pmol/mg of protein) sites were unchanged by ischemia and reperfusion, and NIS did not change binding constants in control or ischemic and reperfused hearts. Increased ET-1 sensitivity after ischemia may be due to other factors. Endothelium-dependent vasodilation and endothelium-independent vasodilation were significantly reduced following 30 min of ischemia. Inhibition of dilator responses may account for increased ET-1 responses following transient ischemia.
Watts
J A
JA
Department of Biology, University of North Carolina, Charlotte 28223.
Chapat
S
S
Johnson
D E
DE
Janis
R A
RA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D015737:Nisoldipine / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D011450:Prostaglandin Endoperoxides, Synthetic; D015737:Nisoldipine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005996:Nitroglycerin; D000109:Acetylcholine