Evaluation of alpha-adrenergic cardiac stimulation in anesthetized dogs: can this play a role in propranolol insensitive cardiostimulatory effects of celiprolol

Abstract

The role of alpha-adrenergic systems in modulating contractility and rate in the canine heart is not completely understood. This was evaluated by examining alpha-agonists and antagonists in ganglionic- and beta-blocked, anesthetized dogs. Also, partial agonist effects of the beta-blocker celiprolol in the ganglionic blocked dog are insensitive to propranolol and may be mediated via alpha-2 antagonism. Prazosin (0.3 mg/kg), yohimbine (0.3 mg/kg), celiprolol (3 mg/kg) and vehicle were administered to ganglionic-(mecamylamine 2 mg/kg) and beta-adrenergic-(propranolol 1 mg/kg + 0.3 mg/kg/hr) blocked dogs. Clonidine (0.3 and 3.0 micrograms/kg), phenylephrine (3 micrograms/kg) and norepinephrine (0.3 microgram/kg) produced significant increases in arterial pressure with minimal chronotropic or inotropic effects. Celiprolol produced sustained increases in heart rate and contractile force of 15 +/- 3 beats/min and 33 +/- 7 percent (X +/- SEM) without significant vascular alpha antagonism. Yohimbine, prazosin and vehicle were without significant chronotropic or inotropic effects. However, yohimbine and prazosin selectively reduced pressor responses to clonidine and phenylephrine, respectively. In further studies adding prazosin or phentolamine before treatment with celiprolol did not attenuate its effects on heart rate and contractility. These results do not support significant inotropic or chronotropic effects of alpha-adrenergic receptor modulation in anesthetized dogs. The cardiac stimulatory effects of celiprolol do not appear to be mediated via cardiac alpha receptors.