Effects of perindopril and carvedilol on endothelium-dependent vascular functions in patients with diabetes and hypertension.
OBJECTIVE
To compare the effects of the ACE inhibitor perindopril and the beta-blocker carvedilol on blood pressure and endothelial functions in NIDDM patients with hypertension.


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.
Giugliano
D
D
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Italy.
Marfella
R
R
Acampora
R
R
Giunta
R
R
Coppola
L
L
D'Onofrio
F
F
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001120:Arginine; D001794:Blood Pressure / Q000187:drug effects; D001809:Blood Viscosity / Q000187:drug effects; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000627:therapeutic use*; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D020913:Perindopril; D010974:Platelet Aggregation / Q000187:drug effects; D011412:Propanolamines / Q000627:therapeutic use*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012212:Rheology / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002227:Carbazoles; D007211:Indoles; D011412:Propanolamines; D000077261:Carvedilol; D001120:Arginine; D020913:Perindopril