Endothelin receptors in the failing and nonfailing human heart.
نویسندگان
چکیده
BACKGROUND In patients with chronic heart failure (CHF), plasma endothelin-1 (ET-1) levels are increased. We studied whether the cardiac ET-receptor system is altered in CHF patients. METHODS AND RESULTS We assessed ET-evoked inositol phosphate (IP) formation in slices from right atria and left ventricles from 6 potential heart transplant donors (NFH) and 15 patients with end-stage CHF; in membranes from the same tissues, we studied ET-induced inhibition of isoprenaline- and forskolin-stimulated adenylyl cyclase and ET-receptor density. ET (10[-9] to 10[-6] mol/L, ET-1 >>> ET-3) increased IP formation in right atria and left ventricles through ET(A)-receptor stimulation in a concentration-dependent manner; no difference in potency or efficacy between NFH and CHF hearts was observed. ET-1 (10[-10] to 10[-6] mol/L), via ET(A)-receptor stimulation, inhibited isoprenaline- and forskolin-stimulated adenylyl cyclase in right atria but not in left ventricles, whereas carbachol inhibited adenylyl cyclase in both tissues; again, the potency and efficacy of ET- or carbachol-induced adenylyl cyclase inhibition was not different between NFH and CHF hearts. [125I]ET-1 binding revealed the coexistence of ET(A) and ET(B) receptors in both tissues; however, the density of ET(A) receptors was not significantly different between NFH and CHF hearts. Finally, the immunodetectable amount of left ventricular Gq/11 protein did not differ between NFH and CHF hearts. CONCLUSIONS In the human heart, ET(A) and ET(B) receptors coexist; however, only ET(A) receptors are of functional importance. In right atria, ET(A) receptors couple to IP formation and inhibition of adenylyl cyclase; in left ventricles, they couple only to IP formation. In end-stage CHF, the functional responsiveness of the cardiac ET(A)-receptor system is not altered.
منابع مشابه
Böhm, Hans-Reinhard Zerkowski and Otto-Erich Brodde
Klaus Pönicke, Magdalene Vogelsang, Moritz Heinroth, Karin Becker, Oliver Zolk, Michael Endothelin Receptors in the Failing and Nonfailing Human Heart Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1998 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation doi: 10.1161/01.CIR.97.8.744...
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ورودعنوان ژورنال:
- Circulation
دوره 97 8 شماره
صفحات -
تاریخ انتشار 1998