α‐SYMPATHOMIMETIC AMINES AND CALCIUM‐MEDIATED ACTION POTENTIALS IN GUINEA‐PIG VENTRICULAR MUSCLE

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Abstract
1 The ability of amines, having α- or α- and β- adrenoceptor stimulating activity, to restore excitability and contractility in heart preparations partially depolarized by potassium, was investigated in guinea-pig ventricular muscle in order to elucidate the mechanism of the positive inotropic effect mediated via α-adrenoceptors. 2 In preparations in which fast sodium channels were inactivated by K+-rich medium (22 mm) slow electrical responses as well as contractions were consistently induced by high concentrations of phenylephrine (10−4 to 3 × 10−4 m) and synephrine (3 × 10−4 m). 3 The restorative effects of both phenylephrine and synephrine were unaffected by phentolamine (10−5 m) but were readily abolished by practolol (10−5 m) or sotalol (10−5 m). 4 Methoxamine induced a dose-dependent positive inotropic effect in ventricular strips paced at 0.5 Hz in normal Tyrode solution; the maximum increase in contractile tension was obtained with methoxamine 10−4 m. However, at the same concentration, the amine did not induce slow electrical responses in potassium-depolarized preparations. 5 It is concluded that the induction of slow responses by phenylephrine and synephrine is due to β-adrenoceptor stimulation, and that the increase in cardiac contractility caused by α-adrenoceptor stimulation does not involve an increase in slow inward calcium current.