title: Calcium antagonist treatment by lercanidipine prevents hyperpolarization in essential hypertension.
abstract: Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxidative stress-induced nitric oxide (NO) breakdown and compensatory production of a hyperpolarizing factor. To test whether calcium antagonist treatment can restore NO availability and prevent hyperpolarization through antioxidant properties, in 15 healthy subjects and 15 patients with essential hypertension, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial bradykinin (5, 15, 50 ng/100 mL per minute), an endothelium-dependent vasodilator, in basal conditions, during infusion of NG-monomethyl-l-arginine (L-NMMA, 100 microg/100 mL per minute), an NO-synthase inhibitor, and ouabain (0.72 microg/100 mL per minute), an Na+-K+ ATPase inhibitor to prevent hyperpolarization. These infusions were repeated in the presence of the antioxidant vitamin C (8 mg/100 mL/min). The response to sodium nitroprusside was also evaluated. In controls, vasodilation to bradykinin was inhibited by L-NMMA and remained unchanged by ouabain or vitamin C. In hypertensive patients, vasodilation to bradykinin was blunted and resistant to L-NMMA but sensitive to ouabain. Vitamin C increased the response to bradykinin and restored the inhibiting effect of L-NMMA while preventing the effect of ouabain. In hypertensive patients, infusions were repeated after 3-month treatment with lercanidipine (10 to 20 mg daily). Lercanidipine decreased plasma lipoperoxides, isoprostanes, and malondialdehyde and increased plasma antioxidant capacity. Moreover, lercanidipine increased the vasodilation to bradykinin and restored the inhibiting effect of L-NMMA on bradykinin-induced vasodilation while preventing the effect of ouabain. Finally, vitamin C no longer exerted its facilitating activity. These results indicate that in essential hypertension, lercanidipine increases endothelium-dependent vasodilation by restoring NO availability and preventing hyperpolarization, an effect probably determined by antioxidant activity.
authors.affiliation: Department of Internal Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. s.taddei@int.med.unipi.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Taddei
authors.forename: Agostino
authors.initials: A
authors.lastname: Virdis
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: Daniele
authors.initials: D
authors.lastname: Versari
authors.forename: Guido
authors.initials: G
authors.lastname: Salvetti
authors.forename: Armando
authors.initials: A
authors.lastname: Magagna
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvetti
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009569:Nitric Oxide; D001205:Ascorbic Acid; C060343:lercanidipine