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Cardioprotective effects of carvedilol on acute autoimmune myocarditis: anti-inflammatory effects associated with antioxidant property.
Am J Physiol Heart Circ Physiol. 2004 Jan; 286(1):H83-90.AJ

Abstract

Carvedilol, a new beta-blocker with antioxidant properties, has been shown to be cardioprotective in experimental models of myocardial damage. We investigated whether carvedilol protects against experimental autoimmune myocarditis (EAM) because of its suppression of inflammatory cytokines and its antioxidant properties. We orally administered a vehicle, various doses of carvedilol, racemic carvedilol [R(+)-carvedilol, an enantiomer of carvedilol without beta-blocking activity], metoprolol, or propranolol to rats with EAM induced by porcine myosin for 3 wk. Echocardiographic study showed that the three beta-blockers, except R(+)-carvedilol, suppressed left ventricular fractional shortening and decreased heart rates to the same extent. Carvedilol and R(+)-carvedilol, but not metoprolol or propranolol, markedly reduced the severity of myocarditis at the two different doses and suppressed thickening of the left ventricular posterior wall in rats with EAM. Only carvedilol suppressed myocardial mRNA expression of inflammatory cytokines and IL-1beta protein expression in myocarditis. In addition, carvedilol and R(+)-carvedilol decreased myocardial protein carbonyl contents and myocardial thiobarbituric acid-reactive substance products in rats with EAM. The in vitro study showed that carvedilol and R(+)-carvedilol suppressed IL-1beta production in LPS-stimulated U937 cells and that carvedilol and R(+)-carvedilol, but not metoprolol or propranolol, suppressed thiobarbituric acid-reactive substance products in myocardial membrane challenged by oxidative stress. It was also confirmed that probucol, an antioxidant, ameliorated EAM in vivo. Carvedilol protects against acute EAM in rats, and the superior cardioprotective effect of carvedilol compared with metoprolol and propranolol may be due to suppression of inflammatory cytokines associated with the antioxidant properties in addition to the hemodynamic modifications.

Authors+Show Affiliations

Dept. of Cardiovascular Medicine, Graduate School of Medicine, Kyoto Univ., 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14684360

Citation

Yuan, Zuyi, et al. "Cardioprotective Effects of Carvedilol On Acute Autoimmune Myocarditis: Anti-inflammatory Effects Associated With Antioxidant Property." American Journal of Physiology. Heart and Circulatory Physiology, vol. 286, no. 1, 2004, pp. H83-90.
Yuan Z, Shioji K, Kihara Y, et al. Cardioprotective effects of carvedilol on acute autoimmune myocarditis: anti-inflammatory effects associated with antioxidant property. Am J Physiol Heart Circ Physiol. 2004;286(1):H83-90.
Yuan, Z., Shioji, K., Kihara, Y., Takenaka, H., Onozawa, Y., & Kishimoto, C. (2004). Cardioprotective effects of carvedilol on acute autoimmune myocarditis: anti-inflammatory effects associated with antioxidant property. American Journal of Physiology. Heart and Circulatory Physiology, 286(1), H83-90.
Yuan Z, et al. Cardioprotective Effects of Carvedilol On Acute Autoimmune Myocarditis: Anti-inflammatory Effects Associated With Antioxidant Property. Am J Physiol Heart Circ Physiol. 2004;286(1):H83-90. PubMed PMID: 14684360.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardioprotective effects of carvedilol on acute autoimmune myocarditis: anti-inflammatory effects associated with antioxidant property. AU - Yuan,Zuyi, AU - Shioji,Keisuke, AU - Kihara,Yasuki, AU - Takenaka,Hiroyuki, AU - Onozawa,Yoko, AU - Kishimoto,Chiharu, PY - 2003/12/20/pubmed PY - 2004/2/21/medline PY - 2003/12/20/entrez SP - H83 EP - 90 JF - American journal of physiology. Heart and circulatory physiology JO - Am J Physiol Heart Circ Physiol VL - 286 IS - 1 N2 - Carvedilol, a new beta-blocker with antioxidant properties, has been shown to be cardioprotective in experimental models of myocardial damage. We investigated whether carvedilol protects against experimental autoimmune myocarditis (EAM) because of its suppression of inflammatory cytokines and its antioxidant properties. We orally administered a vehicle, various doses of carvedilol, racemic carvedilol [R(+)-carvedilol, an enantiomer of carvedilol without beta-blocking activity], metoprolol, or propranolol to rats with EAM induced by porcine myosin for 3 wk. Echocardiographic study showed that the three beta-blockers, except R(+)-carvedilol, suppressed left ventricular fractional shortening and decreased heart rates to the same extent. Carvedilol and R(+)-carvedilol, but not metoprolol or propranolol, markedly reduced the severity of myocarditis at the two different doses and suppressed thickening of the left ventricular posterior wall in rats with EAM. Only carvedilol suppressed myocardial mRNA expression of inflammatory cytokines and IL-1beta protein expression in myocarditis. In addition, carvedilol and R(+)-carvedilol decreased myocardial protein carbonyl contents and myocardial thiobarbituric acid-reactive substance products in rats with EAM. The in vitro study showed that carvedilol and R(+)-carvedilol suppressed IL-1beta production in LPS-stimulated U937 cells and that carvedilol and R(+)-carvedilol, but not metoprolol or propranolol, suppressed thiobarbituric acid-reactive substance products in myocardial membrane challenged by oxidative stress. It was also confirmed that probucol, an antioxidant, ameliorated EAM in vivo. Carvedilol protects against acute EAM in rats, and the superior cardioprotective effect of carvedilol compared with metoprolol and propranolol may be due to suppression of inflammatory cytokines associated with the antioxidant properties in addition to the hemodynamic modifications. SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/14684360/Cardioprotective_effects_of_carvedilol_on_acute_autoimmune_myocarditis:_anti_inflammatory_effects_associated_with_antioxidant_property_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.00536.2003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -