Effect of long-term angiotensin II type I receptor antagonism on peripheral and coronary vasomotion.
Angiotensin II, via AT1 receptors plays a key role in endothelial dysfunction and therefore, in atherogenesis. In order to assess whether long-term blockade of these receptors improve peripheral and coronary endothelial function, 13 patients were treated by candesartan cilexetil (AT2B, 16 mg/d in 10 patients and 8 mg in 3). Flow-mediated dilation (FMD, measured with ultra-sound technique) in the brachial artery and cold pressor testing (CPT)-induced changes in myocardial blood flow (MBF, measured with positron emission tomography) were assessed before and after a 6 month treatment period. AT2B did not alter FMD: 5.0 +/- 1.2% vs. 6.4 +/- 0.9% after treatment. MBF increased significantly during CPT before and after AT2B. Although AT2B did not significantly modify heart rate and blood pressure, MBF normalized to the rate pressure product (MBF/RPP x 10000) was significantly higher and this change remained significant during CPT: it increased from 0.94 +/- 0.05 ml/g/min to 1.14 +/- 0.09 ml/g/min after AT2B (P < .05) and did not decrease during CPT (1.12 +/- 0.08 ml/g/min). Moreover, these AT2B-induced changes in normalized MBF were significantly correlated with the changes in FMD (r = 0.66, P < 0.05). Thus, long-term AT2B improves coronary vasomotion. Although no significant alteration in peripheral conduit endothelial function has been observed, treatment-induced FMD changes seem to be a predictor of coronary circulation improvement.
Preumont
Nicolas
N
Erasme Hospital, Department of Cardiology, Route de Lennik 808, B-1070, Brussels, Belgium. nicolas@preumont.be
Unger
Philippe
P
Goldman
Serge
S
Berkenboom
Guy
G
D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001530:Belgium; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy; D023921:Coronary Stenosis / Q000175:diagnosis / Q000188:drug therapy; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced; D007206:Individuality; D008297:Male; D018579:Patient Selection; D010601:Pharmacology, Clinical / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014463:Ultrasonography / Q000379:methods; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C077793:candesartan cilexetil