Diabetes alters the reactivity of myocardium to a thromboxane analogue

Abstract

Atrial contractile response to U-46619 was studied in auricles from normal and acutely diabetic rats. U-46619 induced an increment of dF/dt in diabetic atria, whereas nondiabetic auricles elicited a negative contractile effect. Blockers of arachidonic acid metabolism via cyclooxygenase inhibited the stimulatory action of U-46619 in diabetic preparations. Moreover, inhibitors of thromboxane synthesis completely blocked the stimulatory effects of U-46619. The stimulant action of the thromboxane A2 mimetic was attenuated when diabetic auricles were incubated with lipoxygenase(s) blocking agents. Results suggest that in diabetic atria, the abnormal inotropic effect induced by U-46619 may be associated with thromboxane formation and with lipoxygenase(s) metabolites.