Effects of α‐adrenoceptor stimulation with phenylephrine in the presence of propranolol on force of contraction, slow inward current and cyclic AMP content in the bovine heart

作者：Reinhard Brückner, Hasso Scholz · 发表于：British Journal of Pharmacology · 年份：1984 · DOI：10.1111/j.1476-5381.1984.tb16462.x · 被引用次数：126 · 研究领域：Cardiac electrophysiology and arrhythmias、Ion channel regulation and function、Neuroscience and Neural Engineering

The mechanism of the cyclic AMP-independent positive inotropic effect of cardiac alpha-adrenoceptor stimulation was studied by analyzing the effects of phenylephrine on force of contraction, calcium-dependent slow action potentials and the slow inward current (Isi) in bovine ventricular trabeculae. The preparations were electrically driven at 0.3 Hz in the presence of propranolol 1 mumol 1(-1). Phenylephrine increased the force of contraction in a concentration-dependent manner (maximum about 200% of control at 30 mumol 1(-1). The effect was surmountably antagonized by phentolamine. The positive inotropic effect of phenylephrine was accompanied by a concentration-dependent increase in time to peak force and occurred without any detectable increase in cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels. The positive inotropic effect of phenylephrine was accompanied by an increase in action potential duration both at 20% and 90% repolarization. Calcium-dependent slow action potentials were also prolonged by phenylephrine and there was a distinct increase in the maximal rate of depolarization (dV/dtmax) of these slow potentials. These effects were also completely reversible on washing and surmountably blocked by phentolamine. However, the increase in dV/dtmax was smaller than that of isoprenaline in concentrations producing similar inotropic effects. Voltage-clamp experiments with the single sucrose-gap method showed that the phenylephrine-induced increase in force of contr...