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Carvedilol, a new vasodilating beta adrenoceptor blocker antihypertensive drug, protects endothelial cells from damage initiated by xanthine-xanthine oxidase and neutrophils.
Cardiovasc Res. 1994 Mar; 28(3):400-6.CR

Abstract

OBJECTIVE

Oxygen radical mediated endothelial injury plays an important role in cardiovascular disease. Carvedilol, a new beta blocker and antihypertensive agent, has been shown to have antioxidant activity. The aim of this study was to determine whether carvedilol protects oxygen radical induced endothelial injury.

METHODS

Cultured bovine pulmonary artery (BPAEC) and human umbilical vein endothelial cells (HUVEC) were used and oxygen radicals were generated by xanthine-xanthine oxidase or phorbol myristate acetate (PMA) activated human neutrophils. Cell injury was assessed by lactate dehydrogenase (LDH) release and cell death, or 51 Cr release from prelabelled BPAEC. The electron paramagnetic resonance (EPR) spin trapping technique was used to detect the amount of radical spin adducts formed in cell lipids.

RESULTS

Carvedilol dose dependently inhibited xanthine-xanthine oxidase induced LDH release from BPAEC and HUVEC, with IC50 values of 3.8 microM and 2.6 microM, respectively, and significantly reduced cell death by xanthine-xanthine oxidase. Other beta blockers tested (propranolol, labetalol, pindolol, and celiprolol) showed a mild effect or no effect at all. Increasing the time of pretreatment with carvedilol enhanced its cell protective effect against oxidative stress. Carvedilol also protected BPAEC dose dependently from PMA activated, neutrophil induced cell injury. Carvedilol had no effect on xanthine oxidase activity. EPR study confirmed that xanthine-xanthine oxidase induced the formation of lipid derived radicals in cell lipids and carvedilol scavenged free radicals, as indicated by the decreased EPR signal.

CONCLUSIONS

Carvedilol protects endothelial cells against oxygen radical mediated cell injury and death by scavenging free radicals. The prevention of oxidative injury to endothelial cells might potentially contribute to the clinical beneficial effects of carvedilol as an antihypertensive agent.

Authors+Show Affiliations

SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7909721

Citation

Yue, T L., et al. "Carvedilol, a New Vasodilating Beta Adrenoceptor Blocker Antihypertensive Drug, Protects Endothelial Cells From Damage Initiated By Xanthine-xanthine Oxidase and Neutrophils." Cardiovascular Research, vol. 28, no. 3, 1994, pp. 400-6.
Yue TL, McKenna PJ, Gu JL, et al. Carvedilol, a new vasodilating beta adrenoceptor blocker antihypertensive drug, protects endothelial cells from damage initiated by xanthine-xanthine oxidase and neutrophils. Cardiovasc Res. 1994;28(3):400-6.
Yue, T. L., McKenna, P. J., Gu, J. L., Cheng, H. Y., Ruffolo, R. E., & Feuerstein, G. Z. (1994). Carvedilol, a new vasodilating beta adrenoceptor blocker antihypertensive drug, protects endothelial cells from damage initiated by xanthine-xanthine oxidase and neutrophils. Cardiovascular Research, 28(3), 400-6.
Yue TL, et al. Carvedilol, a New Vasodilating Beta Adrenoceptor Blocker Antihypertensive Drug, Protects Endothelial Cells From Damage Initiated By Xanthine-xanthine Oxidase and Neutrophils. Cardiovasc Res. 1994;28(3):400-6. PubMed PMID: 7909721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carvedilol, a new vasodilating beta adrenoceptor blocker antihypertensive drug, protects endothelial cells from damage initiated by xanthine-xanthine oxidase and neutrophils. AU - Yue,T L, AU - McKenna,P J, AU - Gu,J L, AU - Cheng,H Y, AU - Ruffolo,R E,Jr AU - Feuerstein,G Z, PY - 1994/3/1/pubmed PY - 2001/3/28/medline PY - 1994/3/1/entrez SP - 400 EP - 6 JF - Cardiovascular research JO - Cardiovasc Res VL - 28 IS - 3 N2 - OBJECTIVE: Oxygen radical mediated endothelial injury plays an important role in cardiovascular disease. Carvedilol, a new beta blocker and antihypertensive agent, has been shown to have antioxidant activity. The aim of this study was to determine whether carvedilol protects oxygen radical induced endothelial injury. METHODS: Cultured bovine pulmonary artery (BPAEC) and human umbilical vein endothelial cells (HUVEC) were used and oxygen radicals were generated by xanthine-xanthine oxidase or phorbol myristate acetate (PMA) activated human neutrophils. Cell injury was assessed by lactate dehydrogenase (LDH) release and cell death, or 51 Cr release from prelabelled BPAEC. The electron paramagnetic resonance (EPR) spin trapping technique was used to detect the amount of radical spin adducts formed in cell lipids. RESULTS: Carvedilol dose dependently inhibited xanthine-xanthine oxidase induced LDH release from BPAEC and HUVEC, with IC50 values of 3.8 microM and 2.6 microM, respectively, and significantly reduced cell death by xanthine-xanthine oxidase. Other beta blockers tested (propranolol, labetalol, pindolol, and celiprolol) showed a mild effect or no effect at all. Increasing the time of pretreatment with carvedilol enhanced its cell protective effect against oxidative stress. Carvedilol also protected BPAEC dose dependently from PMA activated, neutrophil induced cell injury. Carvedilol had no effect on xanthine oxidase activity. EPR study confirmed that xanthine-xanthine oxidase induced the formation of lipid derived radicals in cell lipids and carvedilol scavenged free radicals, as indicated by the decreased EPR signal. CONCLUSIONS: Carvedilol protects endothelial cells against oxygen radical mediated cell injury and death by scavenging free radicals. The prevention of oxidative injury to endothelial cells might potentially contribute to the clinical beneficial effects of carvedilol as an antihypertensive agent. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/7909721/Carvedilol_a_new_vasodilating_beta_adrenoceptor_blocker_antihypertensive_drug_protects_endothelial_cells_from_damage_initiated_by_xanthine_xanthine_oxidase_and_neutrophils_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/28.3.400 DB - PRIME DP - Unbound Medicine ER -