Effects of AT1 receptor antagonism with candesartan on endothelial function in patients with hypertension and coronary artery disease.

Endothelial dysfunction is a major determinant of atherosclerosis and a negative prognostic factor in patients with coronary artery disease and hypertension. Recovery of endothelial dysfunction has been associated with improved prognosis in these patients. The aim of the present study was to verify whether antagonism of angiotensin II AT1 receptors with an angiotensin receptor blocker, candesartan, improved endothelial function in patients with hypertension, stable coronary artery disease, and endothelial dysfunction. We studied 26 patients who were receiving beta-blockers with optimal blood pressure control, in a randomized, double blind study. Patients were randomized to placebo (n=13) or to candesartan 16 mg/d (n=13) for 2 months. Endothelial function was assessed by ultrasound using hyperemic flow-mediated dilation of the brachial artery. Mean arterial blood pressure was unchanged in both groups (from 93.3 +/- 9.2 to 93.2 +/- 17.3 mm Hg in the candesartan group and from 101.3 +/- 14.2 to 102.3 +/- 13.9 mm Hg in the placebo group; both P=ns). Maximal blood flow was similar between placebo and candesartan groups at baseline and at the end of the study, whereas flow-mediated dilation significantly increased in the candesartan group (from 5.27% +/- 1.69% to 7.15% +/- 2.67%; P=0.01) but remained unchanged in the placebo group (from 4.49% +/- 1.97% to 5.88% +/- 2.30%; P=ns). AT1 receptor antagonism with candesartan, in addition to b-blocker therapy, improves endothelial function in high-risk hypertensive patients.