Effects of antihypertensive drugs on alcohol-induced functional responses of cultured human endothelial cells.
Alcohol-induced endothelial changes might contribute to an increase in blood pressure in regular alcohol consumers. Some antihypertensive drugs affect oxidative stress and endothelial function and might counteract the effects of alcohol at the cellular level. The aim of this study was to investigate in vitro the effects of three different types of antihypertensive agents on alcohol-induced endothelial responses and oxidative stress. Cultured human endothelial cells were exposed to increasing concentrations (1, 10, 60 micromol/L) of zofenoprilat, carvedilol, and lacidipine in the absence and in the presence of ethanol (140 mmol/L). Concentrations of endothelin (ET) and nitric oxide (NO) were measured in the culture media as markers of endothelial function, and malondialdehyde (MDA) and intracellular glutathione (GSHi) were measured as markers of oxidative stress. Exposure to alcohol increased the levels of ET, NO, and MDA, and decreased GSHi. Carvedilol and zofenoprilat were more effective than lacidipine in counteracting the effects of alcohol on ET production. Alcohol-induced NO production was enhanced by carvedilol, whereas zofenoprilat and lacidipine did not have a significant effect. The alcohol-induced increase in MDA concentrations was blunted by all three drugs, but only carvedilol restored a normal response. All three drugs increased GSHi levels, with the effect being greater for carvedilol and lacidipine than zofenoprilat. Carvedilol is more effective than zofenoprilat and lacidipine in counteracting alcohol-induced endothelial responses in vitro and in decreasing oxidative stress. These effects might be particularly beneficial in patients with alcohol-related hypertension.
Soardo
Giorgio
G
Division of Internal Medicine-Liver Unit, Department of Experimental and Clinical Pathology and Medicine, University of Udine School of Medicine, Udine, Italy. giorgio.soardo@med.uniud.it
Donnini
Debora
D
Moretti
Massimo
M
Milocco
Carla
C
Catena
Cristiana
C
Sechi
Leonardo A
LA
D000959:Antihypertensive Agents / Q000494:pharmacology*; D002216:Captopril / Q000031:analogs & derivatives / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D008315:Malondialdehyde / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D011412:Propanolamines / Q000494:pharmacology
D000959:Antihypertensive Agents; D002227:Carbazoles; D004095:Dihydropyridines; D011412:Propanolamines; D000077261:Carvedilol; C060285:lacidipine; D009569:Nitric Oxide; D000431:Ethanol; C065520:zofenoprilate; D008315:Malondialdehyde; D002216:Captopril