Enhanced endothelin-1-induced contractions in mesenteric arteries from rats with congestive heart failure: role of ETB receptors

Studies of congestive heart failure (CHF) in man and in experimental CHF ha ve demonstrated elevated circulating levels of endothelin (ET). In order to examine whether there are concomitant ET receptor alterations, the vasomot or effects of endothelin-1 (ET-1) and sarafotoxin 69 (S6c) were examined in endothelium-intact and -denuded isolated mesenteric arteries from rats wit h CHF. CHF was induced by ligation of the left anterior descending coronary artery. Vasomotor responses were studied using small mesenteric arteries ( approx. 250 mum in diameter, determined after normalisation). The antagonis ts IRL2500 and FR139317 were used in order to characterise the ET-l-induced response. In mesenteric arteries with intact endothelium, ET-l-induced con tractions were more potent in CHF as compared to sham (pEC(50) 9.6 +/- 0.2 and 9.1 +/- 0.1, respectively, P < 0.01). In endothelium-denuded arteries, there was no difference in potency of ET-1 between CHF and sham arteries, o r in maximum contraction. In the presence of IRL2500, a selective ETB-recep tor antagonist, ET-1 was more potent in endothelium-denuded arteries of CHF rats, while this difference was not seen in sham arteries. S6c had no cons istent contractile or dilatory effect in CHF and sham rats. The results ind icate that the enhanced contractile effects of ET-1 noted in CHF might be d ue to an attenuated endothelial function and that inhibition of smooth musc le cell ET, receptors increase the effects of contractile ETB receptors in CHF rats. (C) 2001 European Society of Cardiology. Ail rights reserved.