Article date: August 1980
By: F. LEDDA, L. MANTELLI, A. MUGELLI, in Volume 69, Issue 4, pages 565-571
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.
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 × 10−4m) and synephrine (3 × 10−4m).
The restorative effects of both phenylephrine and synephrine were unaffected by phentolamine (10−5m) but were readily abolished by practolol (10−5m) or sotalol (10−5m).
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 10−4m. However, at the same concentration, the amine did not induce slow electrical responses in potassium‐depolarized preparations.
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.
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.
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 × 10−4m) and synephrine (3 × 10−4m).
The restorative effects of both phenylephrine and synephrine were unaffected by phentolamine (10−5m) but were readily abolished by practolol (10−5m) or sotalol (10−5m).
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 10−4m. However, at the same concentration, the amine did not induce slow electrical responses in potassium‐depolarized preparations.
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.
DOI: 10.1111/j.1476-5381.1980.tb07905.x
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