Large and small artery endothelial function in patients with essential hypertension--effect of ACE inhibition and beta-blockade

Abstract

Hypertension has been associated with changes in endothelial function in both large muscular arteries and small resistance arteries. We evaluated the relationship between blood flow velocity and dilatation of the brachial artery following transient forearm ischemia and acetylcholine-induced relaxation in subcutaneous small arteries and the influence of antihypertensive therapy on both in patients with essential hypertension. Thirty-one previously untreated hypertensive patients were randomized in a double-blind fashion to treatment with either the angiotensin-converting enzyme (ACE) inhibitor perindopril or the beta-blocker atenolol and compared with 17 healthy normotensive controls. Before and after 1 year of treatment, while still on active medication, flow-mediated dilatation (FMD) was measured in the brachial artery using ultrasound while relaxation to acetylcholine in small arteries was tested in vitro in a myograph. FMD correlated inversely to resting brachial artery diameter (r = -0.38, p<0.05). FMD corrected for resting diameter (FMD(corr)) was lower in patients (3.0+/-0.2%) compared with controls (4.2+/-0.3%, p<0.01). In both patients and controls, FMD(corr) was related to flow velocity in a non-linear way with FMD(corr) reaching a maximum despite increasing flow velocities, and in the patients, FMD(corr) was only reduced at high flow velocities. Furthermore, patients had a reduced acetylcholine-induced relaxation in small arteries (p = 0.04). Perindopril and atenolol reduced blood pressure to similar levels and both drugs improved FMD(corr) to a similar degree without any effects on relaxation to acetylcholine in small arteries. The present study demonstrates the role of correcting for differences in baseline diameter during measurements of FMD and a non-linear relationship between flow velocity and FMD in the brachial artery. Furthermore, the results suggest different effects of antihypertensive treatment on endothelial function in large and small arteries.