Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension

Essential hypertension is associated with impaired endothelium-dependent va sodilation caused by oxygen free radical-induced nitric oxide (NO) breakdow n. Because calcium antagonists can improve endothelial function in patients with essential hypertension, in this study we tested the hypothesis that t his beneficial effect could be related to restoration of NO availability by antioxidant properties. In 15 healthy subjects and 15 hypertensive patient s, we studied forearm blood flow (strain-gauge plethysmography) modificatio ns induced by intrabrachial acetylcholine (ACh; 0.15, 0.45, 1.5, 4.5, and 1 5 mug/100 mt per minute), an endothelium-dependent vasodilator in basal con ditions, during infusion of N-G-monomethyl-L-arginine (L-NMMA, 100 mug/100 mt forearm tissue per minute), an NO-synthase inhibitor, vitamin C (8 mg/10 0 mt forearm tissue per minute), and finally, simultaneous infusion of L-NM MA and vitamin C. The response to sodium nitroprusside (SNP; 1, 2, and 4 mu g/100 mt forearm tissue per minute) was also evaluated. In control subjects , vasodilation to ACh was inhibited by L-NMMA and not changed by vitamin C. In hypertensive patients, vasodilation to ACh was blunted as compared with control subjects and resistant to L-NMMA. Vitamin C, which decreased plasm a isoprostanes and increased plasma antioxidant capacity, increased the res ponse to ACh and restored the inhibiting effect of L-NMMA. In hypertensive patients, the study was repeated after 3-month treatment with nifedipine ga strointestinal therapeutic system (30 to 60 mg/daily). Nifedipine treatment decreased circulating plasma lipoperoxides and isoprostanes and increased plasma antioxidant capacity. Moreover, nifedipine increased the vasodilatio n to ACh but not to SNP and restored the inhibiting effect of L-NMMA on ACh -induced vasodilation, whereas vitamin C no longer exerted its facilitating activity. These results indicate that nifedipine increases endothelium-dep endent vasodilation by restoring NO availability, an effect probably determ ined by antioxidant activity.