Effect of long-term angiotensin II type I receptor antagonism on peripheral and coronary vasomotion

Abstract

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.