Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction.
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.
Merkus
Daphne
D
Experimental Cardiology, Thoraxcenter, Erasmus MC, Univ. Medical Center Rotterdam, Box 1738, 3000DR Rotterdam, The Netherlands. d.merkus@erasmusmc.nl
Haitsma
David B
DB
Sorop
Oana
O
Boomsma
Frans
F
de Beer
Vincent J
VJ
Lamers
Jos M J
JM
Verdouw
Pieter D
PD
Duncker
Dirk J
DJ
D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000378:metabolism; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001835:Body Weight; D003326:Coronary Circulation / Q000502:physiology; D005080:Exercise Test; D005260:Female; D000077405:Irbesartan; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D009638:Norepinephrine / Q000097:blood; D009929:Organ Size; D010100:Oxygen / Q000378:metabolism; D010805:Physical Conditioning, Animal; D034421:Sus scrofa; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000077405:Irbesartan; D010100:Oxygen; D009638:Norepinephrine