Myocardial alpha-adrenoceptors and positive inotropy.
The positive inotropic effect (PIE) of beta-adrenoceptor stimulating agents in the mammalian heart is mainly due to an increase in slow Ca++ inward current (Isi) which in turn is probably the result of an increase in intracellular cAMP levels. The present paper is concerned with the alpha(probably alpha 1)-adrenoceptor-mediated PIE which differs from the response to beta-adrenoceptor stimulation in several points: it develops relatively slowly, is not accompanied by an abbreviation but instead by a prolongation of the contraction, is dependent on the frequency of stimulation, is increased in hypothyroidism and is not accompanied by detectable changes in cAMP and cGMP levels. In spite of the failure to elevate cAMP levels, alpha-adrenoceptor stimulation increases the magnitude, and decelerates the decay, of Isi. The alpha-adrenoceptor mediated increase in Isi is smaller than that of an equieffective (with respect to the PIE) concentration of isoprenaline. However, this effect conceivably contributes to the alpha-adrenoceptor-mediated PIE although other mechanisms (e.g. an increase in Ca++ sensitivity of the contractile proteins) are likely to be also involved. Recent experiments provide evidence that blockade of beta-adrenoceptors increases the density of myocardial alpha 1-adrenoceptors. This is in accord with the view that stimulation of alpha-adrenoceptors by endogenous catecholamines may serve as a reserve mechanism under conditions of impaired beta-adrenergic influence.
D000818:Animals; D002118:Calcium / Q000502:physiology; D006339:Heart Rate; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008729:Methoxamine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000648:ultrastructure*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013268:Stimulation, Chemical
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D008729:Methoxamine; D007545:Isoproterenol; D002118:Calcium