This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yue, T. L. Articles by Feuerstein, G. Z. Search for Related Content PubMed PubMed Citation Articles by Yue, T. L. Articles by Feuerstein, G. Z. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines Hazardous Substances DB CARVEDILOL

Hypertension, Vol 22, 922-928, Copyright © 1993 by American Heart Association

ARTICLES

Carvedilol, a new antihypertensive agent, prevents lipid peroxidation and oxidative injury to endothelial cells

TL Yue, PJ Mckenna, JL Gu, HY Cheng, RR Ruffolo Jr and GZ Feuerstein
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.

The protective effects of carvedilol, a new beta-adrenergic receptor blocker and vasodilating antihypertensive agent, against oxygen free radical-mediated injury were studied in cultured bovine endothelial cells and compared with five other beta-blockers. Carvedilol dose- dependently inhibited oxygen radical-induced lipid peroxidation (50% inhibition at 2.6 mumol/L) and glutathione depletion (50% inhibition at 1.8 mumol/L) in the cells. Under the same conditions, other beta- blockers--propranolol, labetalol, pindolol, atenolol, and celiprolol-- had only mild or no effect. Moreover, carvedilol protected against oxygen radical--mediated cell damage, as assessed by cellular lactate dehydrogenase release, with a 50% inhibition at 4.1 mumol/L and increased the cell survival in a dose-dependent manner, whereas other beta-blockers had mild or no effects. Pretreatment of the cells with carvedilol for 7 days significantly enhanced the protective effects of carvedilol. Using 2-methyl-2-nitrosopropane as a trapping agent, the spin adduct in cell lipids was monitored by electron paramagnetic resonance. Carvedilol dose-dependently decreased the intensity of the free radical signals, indicating its free radical-scavenging ability. The prevention of oxidative injury to endothelial cells might potentially contribute to the clinical beneficial effects of carvedilol as an antihypertensive agent.

This article has been cited by other articles:

				J.-W. Chen, F.-Y. Lin, Y.-H. Chen, T.-C. Wu, Y.-L. Chen, and S.-J. Lin Carvedilol Inhibits Tumor Necrosis Factor-{alpha}-Induced Endothelial Transcription Factor Activation, Adhesion Molecule Expression, and Adhesiveness to Human Mononuclear Cells Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 2075 - 2081. [Abstract] [Full Text] [PDF]

				M. L. Kukin {beta}-Blockers in Chronic Heart Failure: Considerations for Selecting an Agent Mayo Clin. Proc., November 1, 2002; 77(11): 1199 - 1206. [Abstract] [PDF]

				S. Zitta, K. Stoschitzky, R. Zweiker, K. Oettl, G. Reibnegger, H. Holzer, and W. Estelberger Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension Nephrol. Dial. Transplant., August 1, 2000; 15(8): 1162 - 1169. [Abstract] [Full Text] [PDF]

				F. Romeo, D. Li, M. Shi, and J. L Mehta Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway Cardiovasc Res, February 1, 2000; 45(3): 788 - 794. [Abstract] [Full Text] [PDF]

				M. Takusagawa, S. Komori, K. Matsumura, M. Osada, I. Kohno, K. Umetani, T. Ishihara, T. Sawanobori, H. Ijiri, and K. Tamura The Inhibitory Effects of Carvedilol Against Arrhythmias Induced by Coronary Reperfusion in Anesthetized Rats Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(2): 105 - 112. [Abstract] [PDF]

				J. K. Gwathmey, C. S. Kim, R. J. Hajjar, F. Khan, T. G. DiSalvo, A. Matsumori, and M. R. Bristow Cellular and molecular remodeling in a heart failure model treated with the beta -blocker carteolol Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1678 - H1690. [Abstract] [Full Text] [PDF]

				X. L. Ma, B. L. Lopez, G.-L. Liu, T. A. Christopher, F. Gao, Y. Guo, G. Z. Feuerstein, R. R. Ruffolo Jr, F. C. Barone, and T.-L. Yue Hypercholesterolemia Impairs a Detoxification Mechanism Against Peroxynitrite and Renders the Vascular Tissue More Susceptible to Oxidative Injury Circ. Res., June 19, 1997; 80(6): 894 - 901. [Abstract] [Full Text]

				P. Lesnik, C. Dachet, L. Petit, M. Moreau, S. Griglio, P. Brudi, and M. J. Chapman Impact of a Combination of a Calcium Antagonist and a ß-Blocker on Cell- and Copper-Mediated Oxidation of LDL and on the Accumulation and Efflux of Cholesterol in Human Macrophages and Murine J774 Cells Arterioscler Thromb Vasc Biol, May 1, 1997; 17(5): 979 - 988. [Abstract] [Full Text]