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Brehm Bernhard R.; Heinle, Helmut; Risler, Teut; Wolf, Sabine C.
Journal of Cardiovascular Pharmacology: 2000


In atherosclerosis and heart failure chronically elevated endothelin-1 (ET-1) plasma concentrations have been found which correlate with an increased mortality. The aim of this study was to determine the effects of chronically elevated ET-1 concentrations in vitro on the expression of the β-adrenergic receptor (βAR), the α-subunit of the stimulatory guanine-nucleotide-binding protein (Gsα), and to determine βAR's ability to activate adenylyl cyclase. In order to elucidate the effects of elevated ET-1 concentrations in vivo, male rats were infused with ET-1 and βAR density was measured. Smooth muscle cells were incubated with ET-1 (10-7 mol/l) for 6 to 48 h. Densities of βARs were determined by radioligand binding studies and the Gsα was analyzed by Western blotting. Isoproterenol-mediated adenylyl cyclase activity was measured. Additionally male rats were infused with ET-1 for 3 weeks. In vitro the βAR density increased by 52% (p < 0.05, n = 5). The Gsα increased to 260%. The isoproterenol-stimulated adenylyl cyclase activity was increased to 228%. In vivo, the pulmonary and myocardial βAR density was elevated by 43% and 97%, respectively. Chronic ET receptor activation induces a transregulation of βARs in vitro and in vivo.

Medical Clinic III,*Institute of Physiology, University of Tübingen, Germany

Address correspondence and reprint requests to Bernhard R. Brehm, Medical Clinic III, Otfried-Müllerstr. 10, 72076 Tübingen, Germany. E-mail:

© 2000 Lippincott Williams & Wilkins, Inc.