Effects of Perindopril and Carvedilol on Endothelium-Dependent Vascular Functions in Patients With Diabetes and Hypertension

Abstract

OBJECTIVE To compare the effects of the ACE inhibitor perindopril and the β-blocker carvedilol on blood pressure and endothelial functions in N1DDM patients with hypertension. RESEARCH DESIGN AND METHODS We conducted a double-blind randomized trial in 26 patients with NIDDM and mild hypertension. A 4-week run-in placebo period preceded the active 12-week treatment with perindopril (4–8 mg daily) or carvedilol (25–50 mg daily). Endothelial functions were assessed by evaluating the hemodynamic (mean blood pressure, leg blood flow) and rheological (platelet aggregation, blood viscosity, and blood filterability) responses to an intravenous bolus of 3 g L-arginine, the natural precursor of nitric oxide. RESULTS Both perindopril and carvedilol significantly reduced mean blood pressure (P < 0.001) and increased leg blood flow (P < 0.05) to the same extent; blood filterability remained unchanged in both perindopril- and carvedilol-treated groups. Carvedilol reduced platelet aggregation and blood viscosity significantly (P < 0.05) but perindopril did not. Before treatment, the hemodynamic and rheologic responses to L-arginine were significantly lower in patients (P < 0.05–0.01) than in 20 nondiabetic nonhypertensive control subjects. After 12 weeks of treatment, both drugs normalized the hemodynamic responses to L-arginine. Platelet aggregation response to L-arginine was ameliorated by carvedilol and remained unchanged in the perindopril group. CONCLUSIONS At the doses used, both drugs effectively reduce blood pressure and normalize the hemodynamic responses to L-arginine. The implications of the ameliorated endothelial function for the poor cardiovascular outlook of the NIDDM hypertensive patient need further assessment.