Propranolol therapy in experimental heart failure in rabbits improves cardiac response to catecholamines without beta-adrenoceptor up-regulation.

Abstract

Beta-blockade has been shown to improve cardiac response to catecholamines in heart failure but cellular mechanisms of the improvement are unknown. The effect on left ventricular function of a 14 day propranolol treatment was studied in seven treated and eight non-treated rabbits with experimental heart failure. All animals were subjected to a volume (aortic insufficiency) plus pressure (aortic constriction) overload and were instrumented with a left ventricular catheter and ultrasonic crystals measuring anteroposterior left ventricular diameter. Beta-adrenoceptors were measured using 125I-Cyanopindolol in crude membranes. With isoproterenol, the heart rate was slower in treated rabbits than in non-treated rabbits (p < 0.005) and isoproterenol increased more systolic diameter shortening in treated than in non-treated rabbits (p < 0.05). With norepinephrine, for matched pressures, % delta D increased in the treated group but it did not change in the non-treated group. This improvement of ventricular function was due, in a large part, to an increased diastolic response to norepinephrine: end-diastolic diameter increased in the treated group but not in the non-treated group. In contrast with the improved ventricular response to catecholamines, beta-adrenergic receptor density in the treated group was identical to that of the non-treated group (27.8 fmoles/mg/proteins) and was significantly lower than that of normal rabbits (58.2 fmoles/mg, p < 0.01). The improvement of ventricular response to catecholamines appears to be due to a myocardial protection by propranolol against the toxic effect of catecholamines in heart failure and not, at least in this model, to an up-regulation of beta-adrenoceptors.

• Authors: L Xiong, N E Bouanani, J B Su, B Crozatier
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 9 Issue 6 Pg. 522-30 ( 1995) ISSN: 0767-3981 [Print] England
• PMID: 8808172 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-Agonists
• Adrenergic beta-Antagonists
• Catecholamines
• Receptors, Adrenergic, beta
• cyanopindolol
• Propranolol
• Pindolol
• Isoproterenol
• Norepinephrine

Topics

• Adrenergic alpha-Agonists (pharmacology)
• Adrenergic beta-Antagonists (therapeutic use)
• Animals
• Cardiac Output, Low (drug therapy, physiopathology)
• Catecholamines (blood, metabolism, pharmacology)
• Female
• Heart (drug effects)
• Heart Function Tests
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Isoproterenol (pharmacology)
• Male
• Myocardium (metabolism)
• Norepinephrine (pharmacology)
• Pindolol (analogs & derivatives, pharmacology)
• Propranolol (therapeutic use)
• Rabbits
• Receptors, Adrenergic, beta (biosynthesis)
• Up-Regulation (drug effects)
• Ventricular Function (drug effects)