Increase in atrial contractility induced by PGE2 in diabetic rats.
Contractile response to exogenous prostaglandin E2 (PGE2) was studied in auricles from normal and acutely-diabetic (streptozotocin-treated) rats. In normal atria, PGE2 induced a biphasic inotropic effect negative at low concentrations and positive at higher ones. In diabetic, PGE2 only elicited a positive inotropic action which was greater in efficacy and potency than in normal controls. Incubation of diabetic atrial preparations with alpha-adrenoceptor antagonists (phentolamine, phenoxybenzamine or Prazosin) diminished the prostaglandin effect. However, blockade of beta-adrenoceptors with propranolol did not modify the response. Blockers of arachidonic acid metabolism via cyclo-oxygenase (indomethacin and acetylsalicylic acid) or via lipoxygenase(s) (nordihydroguaiaretic acid and dithizone) were able to reduce the positive inotropism of PGE2. A significant blockade of the stimulant action of PGE2 was seen in the presence of inhibitors of thromboxane synthesis (L-8027 and imidazole). These results suggest that in diabetic atria PGE2 effect could be associated to an involvement of cardiac alpha-adrenergic stimulation which promotes endogenous arachidonic acid release with diversification of its metabolism towards cyclo- and lipoxygenase(s)- pathway and direct to an increased thromboxane formation which could account for the positive inotropic effect induced by PGE2.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015232:Dinoprostone; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011458:Prostaglandins E; D016718:Arachidonic Acid; D013930:Thromboxane-A Synthase; D015232:Dinoprostone