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 rheologicalresponses 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, plateletaggregation, 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 afterL-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 relevanthemodynamic 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.