Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction

• Published in: American journal of physiology. Heart and circulatory physiology 2006-11, Vol.291 (5), p.H2082-H2089
• Main Authors: Merkus, Daphne, Haitsma, David B, Sorop, Oana, Boomsma, Frans, de Beer, Vincent J, Lamers, Jos M. J, Verdouw, Pieter D, Duncker, Dirk J
• Format: Article
• Language: English
• Subjects: Angiotensin II - blood; Angiotensin II - pharmacology; Angiotensin II Type 1 Receptor Blockers - metabolism; Animal behavior; Animals; Biphenyl Compounds - pharmacology; Body Weight; Cardiovascular system; Coronary Circulation - physiology; Coronary vessels; Exercise Test; Female; Heart attacks; Hogs; Male; Myocardial Infarction - etiology; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; Myocardium - pathology; Norepinephrine - blood; Organ Size; Oxygen - metabolism; Physical Conditioning, Animal; Studies; Sus scrofa; Tetrazoles - pharmacology; Time Factors; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasoconstrictor Agents - pharmacology; Vasomotor System - drug effects; Vasomotor System - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00861.2005

1 Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter; 2 Department of Internal Medicine; and 3 Department of Biochemistry, Cardiovascular Research School COEUR, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands Submitted 12 August 2005 ; accepted in final form 6 June 2006 The renin-angiotensin system plays an important role in cardiovascular homeostasis by contributing to the regulation of blood volume, blood pressure, and vascular tone. Because AT 1 receptors have been described in the coronary microcirculation, we investigated whether ANG II contributes to the regulation of coronary vascular tone and whether its contribution is altered during exercise. Since the renin-angiotensin system is activated after myocardial infarction, resulting in an increase in circulating ANG II, we also investigated whether the contribution of ANG II to the regulation of vasomotor tone is altered after infarction. Twenty-six chronically instrumented swine were studied at rest and while running on a treadmill at 1–4 km/h. In 13 swine, myocardial infarction was induced by ligation of the left circumflex coronary artery. Blockade of AT 1 receptors (irbesartan, 1 mg/kg iv) had no effect on myocardial O 2 consumption but resulted in an increase in coronary venous O 2 tension and saturation both at rest and during exercise, reflecting coronary vasodilation. Despite increased plasma levels of ANG II after infarction and maintained coronary arteriolar AT 1 receptor levels, the vasodilation evoked by irbesartan was significantly reduced both at rest and during exercise. In conclusion, despite elevated plasma levels, the vasoconstrictor influence of ANG II on the coronary circulation in vivo is reduced after myocardial infarction. This reduction in ANG II-induced coronary vasoconstriction may serve to maintain perfusion of the remodeled myocardium. renin-angiotensin system; coronary circulation; remodeling; heart failure; autonomic nervous system Address for reprint requests and other correspondence: D. Merkus, Experimental Cardiology, Thoraxcenter, Erasmus MC, Univ. Medical Center Rotterdam, Box 1738, 3000DR Rotterdam, The Netherlands (e-mail: d.merkus{at}erasmusmc.nl )