Multiple effects of putative alpha-adrenoceptor agonists on the electrical and mechanical activity of guinea-pig papillary muscle.

The effects of the putative alpha-adrenoceptor agonists phenylephrine, methoxamine and clonidine on force of contraction and on calcium-dependent action potentials were studied in guinea-pig papillary muscles. Phenylephrine increased the force of contraction by stimulating alpha-adrenoceptors as well as beta-adrenoceptors. It increased the amplitude and duration of slow action potentials, but this effect was exclusively due to stimulation of beta-adrenoceptors. The positive inotropic effect mediated by alpha-adrenoceptors can presumably not be explained by an increase in calcium influx during the action potential via the slow inward current. Methoxamine had no effect on the force of contraction at 10(-5) and 10(-4) mol/l, but at 10(-4) mol/l it slightly decreased amplitude and duration of slow action potentials. Clonidine produced a large increase in force of contraction and in amplitude and duration of slow action potentials. These effects were due to stimulation of H2-histamine receptors. It is concluded that in guinea-pig papillary muscle the tested putative alpha-adrenoceptor agonists do not share a common alpha-adrenoceptor effect, but produce prominent effects which are mediated through either beta-adrenoceptors (phenylephrine), or H2-histamine-receptors (clonidine) or are non-specific (methoxamine) in nature.