The positive inotropic effect of sodium arachidonate on auricles from diabetic rats.
Contractile responses to exogenous sodium arachidonate (NaA) were studied in auricles from normal and acutely diabetic (streptozotocin-treated) rats. NaA induced a concentration-dependent positive inotropic effect in atria from normal and diabetic rats but the magnitude of the contractile influence of the fatty acid was different in both types of auricles, i.e. diabetic atria had a greater responsiveness to NaA than normal preparations. Blockers of arachidonic acid (AA) metabolism via cyclo-oxygenase (indomethacin and acetylsalicylic acid), abolished the stimulatory influence of NaA in normal and in diabetic auricles. Moreover, incubation with tranylcipromine, a prostacyclin synthetase inhibitor, reduced the inotropic effect of NaA in normal atria, but failed to modify it in the diabetic atria. On the other hand, inhibitors of thromboxane (TX) synthetase (imidazole and L-8027) diminished the effect of NaA in diabetic preparations without altering the contractile responses in the controls. In the presence of lipoxygenase blocking agents (nordihydroguaiaretic acid and dithizone), the influence of NaA was reduced at normal values only in the atria from diabetic rats. Both atrial preparations (normal and diabetic) converted ([1-14C]arachidonic acid (AA) into PGI2 (assessed as 6-oxo-PGF1 alpha) and TXB2. Moreover, normal atria generated more PGI2 than TXB2 whereas TXB2 production was greater than that of PGI2 in diabetic atria. The foregoing results suggest that in non-diabetic atria the effect of exogenous NaA may be attributed to metabolites generated by the sequential action of cyclo-oxygenase and prostacyclin synthetase. On the other hand, the contractile action of exogenous NaA in diabetic atria may be ascribed to thromboxanes and lipoxygenase(s) metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D016861:Cyclooxygenase Inhibitors; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D011464:Epoprostenol / Q000037:antagonists & inhibitors; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D011464:Epoprostenol; D013930:Thromboxane-A Synthase