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European Journal of Heart Failure 2001 3(3):293-299; doi:10.1016/S1388-9842(01)00138-6
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© 2001 European Society of Cardiology

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

Anders Bergdahla, Stig Valdemarssona, Mikael Adnera, Xiang-Ying Sunb, Tomas Hednerb and Lars Edvinssona,*

a Department of Internal Medicine, Lund University Hospital 221 85 Lund, Sweden
b Department of Clinical Pharmacology, Gothenburg University Gothenburg, Sweden

* Corresponding author. Tel.: +46-46-17-14-84; fax: +46-46-18-47-92 E-mail address: lars.edvinsson{at}med.lu.se (L. Edvinsson).


  Abstract

Studies of congestive heart failure (CHF) in man and in experimental CHF have demonstrated elevated circulating levels of endothelin (ET). In order to examine whether there are concomitant ET receptor alterations, the vasomotor effects of endothelin-1 (ET-1) and sarafotoxin 6c (S6c) were examined in endothelium-intact and -denuded isolated mesenteric arteries from rats with CHF. CHF was induced by ligation of the left anterior descending coronary artery. Vasomotor responses were studied using small mesenteric arteries (approx. 250 µm in diameter, determined after normalisation). The antagonists IRL2500 and FR139317 were used in order to characterise the ET-1-induced response. In mesenteric arteries with intact endothelium, ET-1-induced contractions were more potent in CHF as compared to sham (pEC50 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, or in maximum contraction. In the presence of IRL2500, a selective ETB-receptor 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 consistent contractile or dilatory effect in CHF and sham rats. The results indicate that the enhanced contractile effects of ET-1 noted in CHF might be due to an attenuated endothelial function and that inhibition of smooth muscle cell ETB receptors increase the effects of contractile ETA receptors in CHF rats.

Key Words: Congestive heart failure • Endothelin-1 • Mesenteric artery • Endothelin A (ETA) • Endothelin B (ETB) • Receptor • In vitro pharmacology

Received July 29, 2000; Revised January 15, 2001; Accepted February 12, 2001


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