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Comparison of pharmacodynamics between carvedilol and metoprolol in rats with isoproterenol-induced cardiac hypertrophy: effects of carvedilol enantiomers.
Eur J Pharmacol. 2008 Jul 28; 589(1-3):194-200.EJ

Abstract

A recent clinical study has shown that carvedilol has a significantly more favorable effect than metoprolol on survival rate in patients with heart failure. This may be due to actions of carvedilol such as beta(2)-adrenoceptor blockade, alpha-adrenergic receptor blockade and other properties such as anti-oxidant effects that are not yet fully understood. We compared the effects of racemic carvedilol, metoprolol and carvedilol enantiomers on cardiac hypertrophy at similar heart rate in rats with isoproterenol-induced cardiac hypertrophy. Continuous administration of isoproterenol for 2 weeks produced heart failure, which is characterized by an increased heart rate, cardiac hypertrophy and downregulation of beta-adrenoceptors. The doses of racemic carvedilol and metoprolol were adjusted to obtain a similar heart rate in rats with isoproterenol-induced cardiac hypertrophy. The reduction of left ventricular weight and improvement of cAMP production induced by carvedilol were superior to those induced by metoprolol. Although heart rate, blood pressure and cAMP production were not affected by R-carvedilol, left ventricular weight was significantly reduced as a result of alpha-adrenoceptor blockade. The improvement of cAMP production by S-carvedilol was significantly higher than that induced by coadministration of R-carvedilol and metoprolol, suggesting that beta(2)-adrenoceptor blockade partly contributed to the improvement of signal transduction in rats with isoproterenol-induced cardiac hypertrophy. This study has demonstrated that the effects of carvedilol on cAMP production and cardiac hypertrophy in rats with isoproterenol-induced cardiac hypertrophy are superior to those induced by metoprolol at a similar heart rate.

Authors+Show Affiliations

Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan. hanada@my-pharm.ac.jp <hanada@my-pharm.ac.jp>No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18534575

Citation

Hanada, Kazuhiko, et al. "Comparison of Pharmacodynamics Between Carvedilol and Metoprolol in Rats With Isoproterenol-induced Cardiac Hypertrophy: Effects of Carvedilol Enantiomers." European Journal of Pharmacology, vol. 589, no. 1-3, 2008, pp. 194-200.
Hanada K, Asari K, Saito M, et al. Comparison of pharmacodynamics between carvedilol and metoprolol in rats with isoproterenol-induced cardiac hypertrophy: effects of carvedilol enantiomers. Eur J Pharmacol. 2008;589(1-3):194-200.
Hanada, K., Asari, K., Saito, M., Kawana, J., Mita, M., & Ogata, H. (2008). Comparison of pharmacodynamics between carvedilol and metoprolol in rats with isoproterenol-induced cardiac hypertrophy: effects of carvedilol enantiomers. European Journal of Pharmacology, 589(1-3), 194-200. https://doi.org/10.1016/j.ejphar.2008.04.055
Hanada K, et al. Comparison of Pharmacodynamics Between Carvedilol and Metoprolol in Rats With Isoproterenol-induced Cardiac Hypertrophy: Effects of Carvedilol Enantiomers. Eur J Pharmacol. 2008 Jul 28;589(1-3):194-200. PubMed PMID: 18534575.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of pharmacodynamics between carvedilol and metoprolol in rats with isoproterenol-induced cardiac hypertrophy: effects of carvedilol enantiomers. AU - Hanada,Kazuhiko, AU - Asari,Kazuhiko, AU - Saito,Masako, AU - Kawana,Jun-Ichi, AU - Mita,Mitsuo, AU - Ogata,Hiroyasu, Y1 - 2008/05/06/ PY - 2008/01/15/received PY - 2008/04/04/revised PY - 2008/04/22/accepted PY - 2008/6/7/pubmed PY - 2008/10/25/medline PY - 2008/6/7/entrez SP - 194 EP - 200 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 589 IS - 1-3 N2 - A recent clinical study has shown that carvedilol has a significantly more favorable effect than metoprolol on survival rate in patients with heart failure. This may be due to actions of carvedilol such as beta(2)-adrenoceptor blockade, alpha-adrenergic receptor blockade and other properties such as anti-oxidant effects that are not yet fully understood. We compared the effects of racemic carvedilol, metoprolol and carvedilol enantiomers on cardiac hypertrophy at similar heart rate in rats with isoproterenol-induced cardiac hypertrophy. Continuous administration of isoproterenol for 2 weeks produced heart failure, which is characterized by an increased heart rate, cardiac hypertrophy and downregulation of beta-adrenoceptors. The doses of racemic carvedilol and metoprolol were adjusted to obtain a similar heart rate in rats with isoproterenol-induced cardiac hypertrophy. The reduction of left ventricular weight and improvement of cAMP production induced by carvedilol were superior to those induced by metoprolol. Although heart rate, blood pressure and cAMP production were not affected by R-carvedilol, left ventricular weight was significantly reduced as a result of alpha-adrenoceptor blockade. The improvement of cAMP production by S-carvedilol was significantly higher than that induced by coadministration of R-carvedilol and metoprolol, suggesting that beta(2)-adrenoceptor blockade partly contributed to the improvement of signal transduction in rats with isoproterenol-induced cardiac hypertrophy. This study has demonstrated that the effects of carvedilol on cAMP production and cardiac hypertrophy in rats with isoproterenol-induced cardiac hypertrophy are superior to those induced by metoprolol at a similar heart rate. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18534575/Comparison_of_pharmacodynamics_between_carvedilol_and_metoprolol_in_rats_with_isoproterenol_induced_cardiac_hypertrophy:_effects_of_carvedilol_enantiomers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00485-8 DB - PRIME DP - Unbound Medicine ER -