Effect of beta-blockers on beta3-adrenoceptor expression in chronic heart failure

Cardiovasc Drugs Ther. 2007 Apr;21(2):85-90. doi: 10.1007/s10557-007-6016-4.

Abstract

Objectives: To investigate the expression of beta(3)-adrenoceptors in rats with chronic heart failure, and to explore the effect of beta-blockers on beta(3)-adrenoceptor expression.

Materials and methods: Thirty-two male Wistar rats were divided into Sham (n = 10) and heart failure (n = 22) groups. The heart failure group was treated with normal saline (Heart Failure Control, n = 6), Metoprolol (n = 8) or Carvedilol (n = 8) for 3 months.

Results: The left ventricular end systolic pressure (LVESP) and the absolute values of maximal rate of rise and fall of left ventricular pressure (+/-dP/dt max) in the heart failure group were lower than in the Sham group (P < 0.01), whereas the left ventricular end diastolic pressure (LVEDP) was higher (P < 0.01). The LVESP and dP/dtmax in the Carvedilol group were higher than the Metoprolol group whereas LVEDP was lower (P < 0.01). The left ventricular mass index (LVMI) in the Carvedilol group was less than the Metoprolol and Heart Failure Control groups (P < 0.01). The level of beta(3)-adrenoceptor expression in the study groups was significantly higher than the Sham group (P < 0.01). beta(3)-adrenoceptor expression in the Carvedilol group was lower than the Heart Failure Control and Metoprolol groups (P < 0.01).

Conclusion: beta(3)-adrenoceptor expression is increased in the failing ventricles in rats. Carvedilol is more effective than Metoprolol for improving the hemodynamics and in attenuating ventricular remodeling after heart failure. Carvedilol, rather than Metoprolol, diminishes beta(3)-adrenoceptor expression in the failing ventricles.

Publication types

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

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Carbazoles / pharmacology
  • Carvedilol
  • Chronic Disease
  • Gene Expression
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Heart Rate / drug effects
  • Male
  • Metoprolol / pharmacology
  • Propanolamines / pharmacology
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-3 / biosynthesis*
  • Receptors, Adrenergic, beta-3 / genetics
  • Vasodilator Agents / pharmacology
  • Ventricular Function, Left / drug effects
  • Ventricular Pressure / drug effects
  • Ventricular Remodeling / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Carbazoles
  • Propanolamines
  • RNA, Messenger
  • Receptors, Adrenergic, beta-3
  • Vasodilator Agents
  • Carvedilol
  • Metoprolol