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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.

OBJECTIVE The endothelium plays a pivotal role in the regulation of vascular tone by releasing nitric oxide (NO). Increased availability of L-arginine, the natural precursor of NO, induces vasodilatation and inhibits platelet activity. We studied the effect of metformin on hemodynamic and rheological responses to L-arginine in patients with NIDDM. RESEARCH DESIGN AND METHODS Ten newly diagnosed NIDDM patients with mild fasting hyperglycemia (7.5 ± 0.3 mmol/l) and without evidence of both micro- and macrovascular complications were investigated. They received an intravenous infusion of L-arginine (1 g/min for 30 min) with evaluation of plasma glucose and insulin, systolic (sBP) and diastolic (dBP) blood pressure, heart rate and plasma catecholamines, platelet aggregation, and blood viscosity and filterability. The L-arginine test was repeated after an 8-week treatment with metformin (850 mg b.i.d.). RESULTS Metformin treatment significantly reduced basal fasting plasma glucose, HbA1c, and platelet aggregation to ADP (P < 0.05); the other parameters did not change. During pretreatment test, L-arginine infusion decreased sBP (from 137 ± 4.1 to 129 ± 4.5 mmHg, P < 0.01) and dBP (from 79 ± 1.9 to 75 ± 1.2 mmHg, P < 0.01) without affecting heart rate or plasma catecholamines. Both platelet aggregation and blood viscosity showed significant decrements after L-arginine, while blood filterability did not change. After metformin treatment, the decrease in blood pressure after L-arginine infusion was significantly enhanced, with a maximal decrease of sBP of 12 ± 3.4 mmHg (8 ± 2.5 mmHg pretreatment, P < 0.05) and dBP of 9.5 ± 2.4 mmHg (4.5 ± 1.9 mmHg pretreatment, P < 0.01). Heart rate, plasma norepinephrine levels, and blood filterability also rose significantly (P < 0.05–0.01). The decrease in both platelet aggregation and blood viscosity after L-arginine was significantly amplified after metformin. CONCLUSIONS We conclude that L-arginine infusion in newly diagnosed NIDDM patients without vascular complications produces relevant hemodynamic and theological changes, which are amplified by an 8-week treatment with metformin. Whether these vascular effects of metformin will improve the poor cardiovascular outlook of the diabetic patient is still unknown.