(Hypertension. 2001;37:943.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Restoration of Nitric Oxide Availability After Calcium Antagonist Treatment in Essential Hypertension
From the Department of Internal Medicine, University of Pisa (Italy), and the Department of Pathophysiology and Experimental Medicine (A.P.), University of Siena (Italy).
Correspondence to Stefano Taddei, MD, Department of Internal Medicine, University of Pisa, Via Roma 67, 56100 Pisa, Italy. E-mail s.taddei{at}int.med.unipi.it
Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical–induced nitric oxide (NO) breakdown. Because calcium antagonists can improve endothelial function in patients with essential hypertension, in this study we tested the hypothesis that this beneficial effect could be related to restoration of NO availability by antioxidant properties. In 15 healthy subjects and 15 hypertensive patients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (ACh; 0.15, 0.45, 1.5, 4.5, and 15 µg/100 mL per minute), an endothelium-dependent vasodilator in basal conditions, during infusion of NG-monomethyl-L-arginine (L-NMMA, 100 µg/100 mL forearm tissue per minute), an NO-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), and finally, simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (SNP; 1, 2, and 4 µg/100 mL 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 plasma isoprostanes and increased plasma antioxidant capacity, increased the response to ACh and restored the inhibiting effect of L-NMMA. In hypertensive patients, the study was repeated after 3-month treatment with nifedipine gastrointestinal therapeutic system (30 to 60 mg/daily). Nifedipine treatment decreased circulating plasma lipoperoxides and isoprostanes and increased plasma antioxidant capacity. Moreover, nifedipine increased the vasodilation 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-dependent vasodilation by restoring NO availability, an effect probably determined by antioxidant activity.
Key Words: hypertension, essential • endothelium • nitric oxide • endothelium-derived factors • free radicals • antioxidants • calcium antagonists
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