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: 288/2/H871    most recent 00429.2004v1 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 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 Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Merkus, D. Articles by Duncker, D. J. Search for Related Content PubMed PubMed Citation Articles by Merkus, D. Articles by Duncker, D. J.

Contribution of endothelin to coronary vasomotor tone is abolished after myocardial infarction

¹Experimental Cardiology, Thoraxcenter, and ²Internal Medicine, Cardiovascular Research School Rotterdam, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

Submitted 6 May 2004 ; accepted in final form 25 September 2004

Left ventricular dysfunction in swine with a recent myocardial infarction (MI) is associated with neurohumoral activation, including increased catecholamines and endothelin (ET). Although the increase in ET may serve to maintain blood pressure and, hence, perfusion of essential organs such as the heart and brain, it could also compromise myocardial perfusion by evoking coronary vasoconstriction. In the present study, we tested the hypothesis that endogenous ET contributes to perturbations in myocardial O₂ balance during exercise in remodeled myocardium of swine with a recent MI. For this purpose, 26 chronically instrumented swine (10 with and 16 without MI) were studied at rest and while running on a treadmill at 1–4 km/h. After MI, plasma ET increased from 3.2 ± 0.4 to 4.9 ± 0.3 pM (P < 0.05). In normal swine, blockade of ET_A (by EMD-122946) or ET_A-ET_B (by tezosentan) receptors resulted in an increase in coronary venous PO₂, i.e., coronary vasodilation at rest, which decreased during exercise. In contrast, neither ET_A nor ET_A-ET_B receptor blockade resulted in coronary vasodilation in swine with MI. Coronary vasoconstriction to intravenous ET-1 infusion in awake resting swine was blunted after MI. To investigate whether factors released by cardiac myocytes contributed to decreased vascular responsiveness to ET, we performed ET-1 dose-response curves in isolated coronary arterioles (70–200 µm). Vasoconstriction to ET-1 in isolated arterioles from MI swine was enhanced. In conclusion, the vasoconstrictor influence of endogenous as well as exogenous ET on coronary circulation in vivo is reduced. Because the response of isolated coronary arterioles to ET is increased after MI, the reduced vasoconstrictor influence in vivo suggests modulation of ET receptor sensitivity by cardiac myocytes, which may serve to maintain adequate myocardial perfusion.

coronary microcirculation; coronary blood flow; myocardial oxygen balance; left ventricular dysfunction

This article has been cited by other articles:

				V. J. de Beer, O. Sorop, D. A. Pijnappels, D. H. Dekkers, F. Boomsma, J. M. J. Lamers, D. J. Duncker, and D. Merkus Integrative control of coronary resistance vessel tone by endothelin and angiotensin II is altered in swine with a recent myocardial infarction Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2069 - H2077. [Abstract] [Full Text] [PDF]

				D. Konrad, M. Haney, G. Johansson, M. Wanecek, E. Weitzberg, and A. Oldner Cardiac effects of endothelin receptor antagonism in endotoxemic pigs Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H988 - H996. [Abstract] [Full Text] [PDF]

				D. Merkus, B. Houweling, V. J. de Beer, Z. Everon, and D. J. Duncker Alterations in endothelial control of the pulmonary circulation in exercising swine with secondary pulmonary hypertension after myocardial infarction J. Physiol., May 1, 2007; 580(3): 907 - 923. [Abstract] [Full Text] [PDF]

				D. Merkus, D. B. Haitsma, O. Sorop, F. Boomsma, V. J. de Beer, J. M. J. Lamers, P. D. Verdouw, and D. J. Duncker Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2082 - H2089. [Abstract] [Full Text] [PDF]

				I. Bak, I. Lekli, B. Juhasz, N. Nagy, E. Varga, J. Varadi, R. Gesztelyi, G. Szabo, L. Szendrei, I. Bacskay, et al. Cardioprotective mechanisms of Prunus cerasus (sour cherry) seed extract against ischemia-reperfusion-induced damage in isolated rat hearts Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1329 - H1336. [Abstract] [Full Text] [PDF]

				B. Houweling, D. Merkus, O. Sorop, F. Boomsma, and D. J. Duncker Role of endothelin receptor activation in secondary pulmonary hypertension in awake swine after myocardial infarction J. Physiol., July 15, 2006; 574(2): 615 - 626. [Abstract] [Full Text] [PDF]