Positive inotropic effects of phenylephrine in the isolated rabbit papillary muscle mediated both by α-and β-adrenoceptors

Summary

On the isolated papillary muscle of the rabbit experiments were performed in order to study whether β-and/or α-adrenoceptors mediate the positive inotropic effect of phenylephrine and, for comparison, of other sympathomimetic drugs.

• 1. The positive inotropic effect of phenylephrine in concentrations of up to 3×10⁻⁶M was antagonized by the α-adrenolytic drug phentolamine, while that evoked by higher concentrations was inhibited by the β-adrenolytic drug pindolol. The intrinsic activity of phenylephrine amounted to 0.6 compared with that of isoprenaline.

• 2. Pretreatment with reserpine altered neither the pD₂-value for phenylephrine nor its intrinsic activity.

• 3. The inhibitors of phosphodiesterase, theophylline (10⁻⁴M) and papaverine (10⁻⁵M) enhanced the effect of higher concentrations of phenylephrine—mediated mainly by stimulation of β-adrenoceptors, whereas that of lower concentrations—mediated by stimulation of α-adrenoceptors—was not affected. Papaverine strongly increased the intrinsic activity of phenylephrine, which then reached that of isoprenaline.

• 4. The α-adrenoceptor stimulating drugs, methoxamine, naphazoline and oxymetazoline did not cause positive inotropic effects but, on the contrary, negative ones. The positivei notropic effect of noradrenaline was not changed by phentolamine, whereas that of adrenaline in concentrations of up to 10⁻⁵ M was inhibited.

• 5. From these results it is concluded that in the rabbit papillary muscle not only β- but also α-adrenoceptors are of functional importance for the mediation of the positive inotropic effect of some sympathomimetic drugs. The nature of these α-adrenoceptors is apparently distinct from those of other organs since these receptors were stimulated only by phenylephrine and adrenaline but not by noradrenaline, methoxamine, naphazoline and oxymetazoline.