[Underlying mechanisms of inotropic effects mediated by alpha-adrenoceptors in mammalian left atria--influences of stimulation frequencies and Ca++ channel blocking agents--].
Experiments were performed in the electrically driven left atria of guinea pigs, rabbits and rats in order to clarify the inotropic mechanisms of myocardial alpha-adrenoceptor stimulation. In the left atria of guinea pigs stimulated of 0.2 Hz, stimulation of alpha-adrenoceptors produced triphasic time response curves which composed of an initial positive inotropic phase followed by a negative phase and then a second positive phase. The negative inotropic effect leading to the occurrence of the triphasic time course was depend on concentration of phenylephrine and stimulation frequency, i.e. it became more manifest with increase in the concentration of phenylephrine and with decrease in stimulation frequency. Phenoxybenzamine blocked both the positive and the negative phase. Phentolamine and yohimbine preferentially inhibited the negative phase while prazosin preferentially depressed the positive phase. These results suggest that two populations of alpha-adrenoceptors might be present; one stimulatory and one inhibitory. In the left atria of rabbits, alpha-adrenoceptor stimulation increased the contractile force at rates more than 0.5 Hz, whereas the same procedure resulted in a negative inotropic effect at 1 beat/min. Rested state contractions were significantly decreased by alpha-adrenoceptor stimulation, while increased by beta-adrenoceptor stimulation. Post rest contractions, when NaCl concentration was reduced to 50%, was significantly diminished by alpha-adrenoceptor stimulation in contract with significant increase by beta-adrenoceptor stimulation. In the left atria of rats, alpha-adrenoceptor stimulation did not strongly influence a negative staircase whereas beta-adrenoceptor stimulation abolished it. In the partially depolarized preparations, alpha-adrenoceptor stimulation did not always restore the mechanical responses. Lower concentration of Ca++ channel blocking agents, which are known not to inhibit the slow inward current, significantly depressed the alpha-mimetic positive inotropic effect. These results indicate that the positive inotropic mechanisms of alpha-adrenoceptor stimulation might be closely related to the surface Ca++ rather than to an enhancement of the slow inward current.
D000818:Animals; D016275:Atrial Function; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007477:Ions; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013045:Species Specificity
D002121:Calcium Channel Blockers; D007477:Ions; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D002118:Calcium