Are prostanoids related to positive inotropism by UTP and ATP ?

Uridine 5'-triphosphate (UTP) and adenosine 5'-triphosphate (ATP) induce biphasic inotropic effects: first a decrease and then an increase in contractile tension were observed in isolated rat myocardial tissues. Inotropic effects were higher in atrial tissue than in ventricular or papillary muscle; thus, experiments were mostly carried out on rat atria. In this research, we mainly studied positive inotropism by using selective inhibitors of the arachidonic acid cascade. The natural compounds luffariellolide and aristolochic acid, two inhibitors of PLA2, both inhibited positive inotropism by UTP but not by ATP, whereas they did not modify their negative inotropism. Indomethacin (5 micromol/l), an inhibitor of COX-1, reduced positive inotropism by UTP but not by ATP, without modifying their negative inotropism. Nimesulide (1 micromol/l), an inhibitor of COX-2, did not change any of the effects caused by nucleotides. Nor did NDGA (10 micromol/l), an inhibitor of lipoxygenase, change inotropism by nucleotides. Arachidonic acid pretreatment (10 micromol/l) increased inotropic effects by UTP without affecting those of ATP. These data suggest that there are differences in the mechanisms responsible for the positive inotropism caused by UTP in comparison with ATP; the effect of UTP depends on PLA2 activation and PG(s) release, whereas that of ATP does not.