Propranolol therapy in experimental heart failure in rabbits improves cardiac response to catecholamines without beta-adrenoceptor up-regulation.
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.
Xiong
L
L
Inserm U400, Faculté de Médecine, Créteil, France.
Bouanani
N E
NE
Su
J B
JB
Crozatier
B
B
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011433:Propranolol / Q000627:therapeutic use*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; C047975:cyanopindolol; D011433:Propranolol; D010869:Pindolol; D007545:Isoproterenol; D009638:Norepinephrine