HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/H1194    most recent 00563.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Leite-Moreira, A. F. Articles by Brás-Silva, C. Search for Related Content PubMed PubMed Citation Articles by Leite-Moreira, A. F. Articles by Brás-Silva, C.

Inotropic effects of ET_B receptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins

Department of Physiology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal

Submitted 16 June 2003 ; accepted in final form 4 May 2004

Endothelin (ET)-1 acts on ET_A and ET_B receptors. The latter include ET_B1 (endothelial) and ET_B2 (muscular) subtypes, which mediate opposite effects on vascular tone. This study investigated, in rabbit papillary muscles (n = 84), the myocardial effects of ET_B stimulation. ET-1 (10^–9 M) was given in the absence or presence of BQ-123 (ET_A antagonist). The effects of IRL-1620 (ET_B1 agonist, 10^–10–10^–6 M) or sarafotoxin S6c (ET_B agonist, 10^–10–10^–6 M) were evaluated in muscles with intact or damaged endocardial endothelium (EE); intact EE, in the presence of N^G-nitro-L-arginine (L-NNA); and intact EE, in the presence of indomethacin (Indo). Sarafotoxin S6c effects were also studied in the presence of BQ-788 (ET_B2 antagonist). ET-1 alone increased 64 ± 18% active tension (AT) but decreased it by 4 ± 2% in the presence of BQ-123. In muscles with intact EE, sarafotoxin S6c alone did not significantly alter myocardial performance. Sarafotoxin S6c (10^–6 M) increased, however, AT by 120 ± 27% when EE was damaged and by 39 ± 8% or 23 ± 6% in the presence of L-NNA or Indo, respectively. In the presence of BQ-788, sarafotoxin S6c decreased AT (21 ± 3% at 10^–6 M) in muscles with intact EE, an effect that was abolished when EE was damaged. IRL-1620 also decreased AT (22 ± 3% at 10^–6 M) in muscles with intact EE, an effect that was abolished when EE was damaged or in the presence of L-NNA or Indo. In conclusion, the ET_B-mediated negative inotropic effect is presumably due to ET_B1 stimulation, requires an intact EE, and is mediated by NO and prostaglandins, whereas the ET_B-mediated positive inotropic effect, observed when EE was damaged or NO and prostaglandins synthesis inhibited, is presumably due to ET_B2 stimulation.

heart; endothelins; endothelial function; contractile function; nitric oxide

This article has been cited by other articles:

				R. Mazza, A. Gattuso, C. Mannarino, B. K. Brar, S. F. Barbieri, B. Tota, and S. K. Mahata Catestatin (chromogranin A344-364) is a novel cardiosuppressive agent: inhibition of isoproterenol and endothelin signaling in the frog heart Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H113 - H122. [Abstract] [Full Text] [PDF]

				A. P. Lourenco, R. Roncon-Albuquerque Jr., C. Bras-Silva, B. Faria, J. Wieland, T. Henriques-Coelho, J. Correia-Pinto, and A. F. Leite-Moreira Myocardial dysfunction and neurohumoral activation without remodeling in left ventricle of monocrotaline-induced pulmonary hypertensive rats Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1587 - H1594. [Abstract] [Full Text] [PDF]

				C. Bras-Silva and A. F. Leite-Moreira Obligatory role of the endocardial endothelium in the increase of myocardial distensibility induced by endothelin-1. Experimental Biology and Medicine, June 1, 2006; 231(6): 876 - 881. [Abstract] [Full Text] [PDF]

				C. Bras-Silva, A. P. Fontes-Sousa, C. Moura, J. C. Areias, and A. F. Leite-Moreira Impaired Response to ETB Receptor Stimulation in Heart Failure: Functional Evidence of Endocardial Endothelial Dysfunction? Experimental Biology and Medicine, June 1, 2006; 231(6): 893 - 898. [Abstract] [Full Text] [PDF]