Mechanisms of positive inotropic effects.
This review deals with the principal mechanisms which are known to play a role in positive inotropism: 1) The myoplasmic Ca2+ concentration may be increased by increases in cyclic AMP. Beside receptor-mediated stimulation (isoprenaline) or direct stimulation (forskolin) of the adenylate cyclase, the cyclic AMP may be increased by phosphodiesterase inhibition; 2) Cyclic AMP-independent activation of Ca2+ channels can be brought about by alpha-adrenergic agents (phenylephrine) or so-called calcium agonists; 3) Only a small increase in myoplasmic Na+ concentration can greatly enhance the force of contraction by an increase in the intracellular Ca2+ concentration. This is possible by inhibition of the Na+/K+-ATPase (glycosides) or by prolongation of the open state of Na+ channels (DPI 201-106); 4) A direct inhibition of the Na+/Ca2+ exchange has been discussed for amiloride; 5) A prolongation of the action potential induced by K+ channel-inhibiting agents such as 4-amino-pyridine may increase the myoplasmic Ca2+ concentration by a prolongation of the slow Ca2+ inward current; 6) An increased Ca2+ sensitivity of the contractile proteins has been demonstrated for a number of compounds in vitro; the contribution of such an effect to the overall positive inotropism is unknown because a calcium sensitizer without any effects on calcium or sodium movements is not yet available.
Scholz
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Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, FRG.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects*; D013268:Stimulation, Chemical
D002316:Cardiotonic Agents; D000242:Cyclic AMP; D002118:Calcium