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1 Experimental Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, Netherlands
2 Internal Medicine, Erasmus MC, Rotterdam, Netherlands
3 Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
4 Lab for Experimental Cardiology, Erasmus University Rotterdam, P.O. Box 1738, Rotterdam, 3000 DR, Netherlands; Experimental Cardiology, Thoraxcenter, Erasmus MC, Rotterdam, Netherlands
* To whom correspondence should be addressed. E-mail: d.merkus{at}erasmusmc.nl.
The renin-angiotensin system plays an important role in cardiovascular homeostasis by contributing to the regulation of blood volume, blood pressure and vascular tone. Since AT1-receptors have been described in the coronary microcirculation, we investigated whether angiotensin II (ANG-II) contributes to the regulation of coronary vascular tone and if 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 if 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 AT1-receptors (irbesartan, 1mg/kg, i.v.) had no effect on myocardial O2 consumption but resulted in an increase in coronary venous O2 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 AT1-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.
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