Objective: The nitric oxide (NO) system is abnormal in essential hypertension and the response of the forearm vascular bed to local intra-arterial infusions of NG-monomethyl-L-arginine (L-NMMA) is diminished in patients with untreated essential hypertension. Animal data suggest that treatment of hypertension may restore normal NO-mediated responses. We have prospectively examined the effect of standard antihypertensive therapy on the responsiveness to local intra-arterial infusions of L-NMMA in 18 newly diagnosed hypertensive patients.
Design: This was a double-blind, randomized, parallel-group study. Patients were randomized to treatment with 10 mg enalapril daily, 5 mg amlodipine daily or matched placebo for 6 weeks (with dose titration after 2 weeks if necessary).
Methods: Forearm blood flow during direct infusion into the brachial artery of L-NMMA (1, 2 and 4 mumol/min) was measured using venous occlusion plethysmography at the beginning and end of the 6-week treatment period.
Results: Both enalapril and amlodipine reduced blood pressure significantly compared with placebo. After 6 weeks of antihypertensive therapy, forearm blood flow (+/- SEM) in response to the maximum dose of L-NMMA (4 mumol/min) was reduced by 54.8 (6.9)% (P = 0.012), 58.9 (7.0)% (P = 0.016) and 33.1 (3.0)% (P = 0.17) in the enalapril, amlodipine and placebo groups, respectively. There was no significant difference between enalapril and amlodipine treatment groups.
Conclusions: The forearm arterial responsiveness to L-NMMA in newly diagnosed patients with essential hypertension returns to normal with normalization of blood pressure by antihypertensive drugs with different modes of action. It remains to be determined whether this phenomenon is a consequence of the change in pressure per se or a result of the action of either drug by a common or separate mechanism.