Endothelin: differential effects in vascular and nonvascular smooth muscle.
Endothelin, a potent vasoconstrictor, produced concentration-dependent contractions in aorta, trachea and bladder body obtained from rat and rabbit. Contractions developed slowly, reaching maxiMum within 15-20 min. Although, in both rat and rabbit tissues, endothelin was 3- to 10-fold more potent in contracting vascular (approximate EC50, 1 nM) than nonvascular smooth muscle, rat trachea and rabbit bladder did contract in response to endothelin. Rat bladder body and rabbit trachea were the least sensitive tissues with only modest contractile responses to endothelin. To determine the role of calcium in these endothelin-induced contractions, the effects of diltiazem and nitrendipine were examined. Although diltiazem (5 x 10-5) M) or nitrendipine (10(-6) M) markedly attenuated contractions produced by KCl, neither agent significantly affected concentration response curves produced by endothelin in rabbit aorta or rat trachea. In rat aorta, nitrendipine had no effect on endothelin responses, whereas diltiazem modestly decreased the maximal contraction to endothelin. However, in rabbit bladder, both calcium channel blockers significantly decreased the maximum response to endothelin with no change in EC50. These results indicate that smooth muscle sensitivity to the contractile effects of endothelin may be both species and tissue specific.
Secrest
R J
RJ
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Cohen
M L
ML
D000818:Animals; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014132:Trachea; D001743:Urinary Bladder
D016232:Endothelins; D010455:Peptides; D009568:Nitrendipine; D004110:Diltiazem