OBJECTIVES: Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown. Since calcium antagonists can improve endothelial function in hypertensive patients, we tested whether this beneficial effect could be related to restoration of NO availability by antioxidant activity. METHODS: In 10 healthy subjects and 20 essential hypertensive patients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (from 0.15-15microg/100 ml per min), bradykinin (0.005-0.05 microg/100 ml per min), two endothelium-dependent vasodilators, and sodium nitroprusside (1-4 microg/100 ml forearm tissue per min), an endothelium independent vasodilator, in the absence and presence of NG-monomethyl-L-arginine (L-NMMA) (100 microg/100 ml forearm tissue per min), an NO synthase inhibitor. RESULTS: In controls, vasodilation to acetylcholine and bradykinin was inhibited 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 lacidipine (4-6 mg/daily) or atenolol (50-100 mg/daily) (n = 10 each group). Lacidipine but not atenolol increased the vasodilation to acetylcholine and bradykinin and restored the inhibiting effect of L-NMMA on endothelium-dependent vasodilation, without affecting the response to sodium nitroprusside. Moreover, lacidipine reduced circulating markers of oxidative stress including plasma and low-density lipoprotein (LDL) hydroperoxides, the susceptibility of LDL to Cu2+-induced oxidation and the reactive oxygen species generated from human umbilical vein endothelial cells after incubation with LDL derived from plasma of the patients. CONCLUSIONS:Lacidipine increases endothelium-dependent vasodilation by restoring NO availability, and this effect possibly is related to antioxidant activity.
RCT Entities:
OBJECTIVES: Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown. Since calcium antagonists can improve endothelial function in hypertensivepatients, we tested whether this beneficial effect could be related to restoration of NO availability by antioxidant activity. METHODS: In 10 healthy subjects and 20 essential hypertensivepatients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (from 0.15-15 microg/100 ml per min), bradykinin (0.005-0.05 microg/100 ml per min), two endothelium-dependent vasodilators, and sodium nitroprusside (1-4 microg/100 ml forearm tissue per min), an endothelium independent vasodilator, in the absence and presence of NG-monomethyl-L-arginine (L-NMMA) (100 microg/100 ml forearm tissue per min), an NO synthase inhibitor. RESULTS: In controls, vasodilation to acetylcholine and bradykinin was inhibited by L-NMMA. In hypertensivepatients, vasodilation to acetylcholine and bradykinin, but not to sodium nitroprusside, was blunted and resistant to L-NMMA. Hypertensivepatients were randomized to a 12-week treatment with lacidipine (4-6 mg/daily) or atenolol (50-100 mg/daily) (n = 10 each group). Lacidipine but not atenolol increased the vasodilation to acetylcholine and bradykinin and restored the inhibiting effect of L-NMMA on endothelium-dependent vasodilation, without affecting the response to sodium nitroprusside. Moreover, lacidipine reduced circulating markers of oxidative stress including plasma and low-density lipoprotein (LDL) hydroperoxides, the susceptibility of LDL to Cu2+-induced oxidation and the reactive oxygen species generated from human umbilical vein endothelial cells after incubation with LDL derived from plasma of the patients. CONCLUSIONS:Lacidipine increases endothelium-dependent vasodilation by restoring NO availability, and this effect possibly is related to antioxidant activity.
Authors: Denisa Celovska; Peter Kruzliak; Luis Rodrigo; Jozef Gonsorcik; Peter Sabaka; Peter Gaspar; Delian Delev; Daniel Petrovic; Andrej Dukat; Ludovit Gaspar Journal: High Blood Press Cardiovasc Prev Date: 2016-05-09
Authors: Diogo M O Marçal; Elen Rizzi; Alisson Martins-Oliveira; Carla S Ceron; Danielle A Guimaraes; Raquel F Gerlach; Jose E Tanus-Santos Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2010-10-31 Impact factor: 3.000
Authors: Holly N Thomas; Gregory W Evans; Dan R Berlowitz; Glenn M Chertow; Molly B Conroy; Capri G Foy; Stephen P Glasser; Cora E Lewis; William T Riley; Laurie Russell; Olubunmi Williams; Rachel Hess Journal: J Hypertens Date: 2016-06 Impact factor: 4.844