Influence of cyclooxygenase inhibitors and of lithium on the positive inotropic effect mediated by alpha 1-adrenoceptors in guinea-pig left atrium.

In experiments on the isolated guinea-pig left atrium we tried to get more information about the intracellular signal transmission of the alpha 1-adrenoceptor. We were able to demonstrate that the cyclooxygenase inhibitors indometacin and acetylsalicylic acid enhance the positive inotropic effect of relatively low phenylephrine concentrations at an extracellular calcium concentration of 1.22 mmol/l. Preincubation with prazosin as well as an increased calcium concentration of 2.5 mmol/l abolished this effect. These observations led us to suppose that an elevated level of receptor-generated arachidonic acid, whose degradation is inhibited by the cyclooxygenase inhibitors, caused the increased contractility by releasing more calcium from the sarcoplasmic reticulum. Under these conditions also lithium caused a distinct enhancement of the positive inotropic effect evoked by alpha 1-adrenergic agonists, probably by inhibiting the degradation of the second messenger inositol trisphosphate.