Effect of calcium antagonist or beta blockade treatment on nitric oxide-dependent vasodilation and oxidative stress in essential hypertensive patients

Objectives Essential hypertension is associated with impaired endothelium-d ependent vasodilation caused by oxygen free radical-induced nitric oxide (N O) breakdown. Since calcium antagonists can improve endothelial function in hypertensive patients, we tested whether this beneficial effect could be r elated to restoration of NO availability by antioxidant activity. Methods In 10 healthy subjects and 20 essential hypertensive patients, we s tudied forearm blood flow (strain-gauge plethysmography) modifications indu ced by intrabrachial acetylcholine (from 0.15-15 mug/100 ml per min), brady kinin (0.005-0.05 mug/100 ml per min), two endothelium-dependent vasodilato rs, and sodium nitroprusside (1-4 mug/100 ml forearm tissue per min), an en dothelium independent vasodilator, in the absence and presence of N-G-monom ethyl-L-arginine (L-NMMA) (100 mug/100 ml forearm tissue per min), an NO sy nthase inhibitor. Results In controls, vasodilation to acetylcholine and bradykinin was inhib ited by L-NMMA. In hypertensive patients, vasodilation to acetylcholine and bradykinin, but not to sodium nitroprusside, was blunted and resistant to L-NMMA. Hypertensive patients were randomized to a 12-week treatment with l acidipine (4-6 mg/daily) or atenolol (50-100 mg/daily) (n = 10 each group). Lacidipine but not atenolol increased the vasodilation to acetylcholine an d bradykinin and restored the inhibiting effect Of L-NMMA on endothelium-de pendent vasodilation, without affecting the response to sodium nitroprussid e. Moreover, lacidipine reduced circulating markers of oxidative stress inc luding plasma and low-density lipoprotein (LDL) hydroperoxides, the suscept ibility of LDL to Cu2+-Induced oxidation and the reactive oxygen species ge nerated from human umbilical vein endothelial cells after incubation with L DL derived from plasma of the patients. Conclusions Lacidipine increases endothelium-dependent vasodilation by rest oring NO availability, and this effect possibly is related to antioxidant a ctivity. (C) 2001 Lippincott Williams & Wilkins.