Hypersensitivity to norepinephrine in vasa deferentia from diabetic rats. Possible participation of metabolic products of arachidonic acid.
Contractile responses to norepinephrine of the vas deferens isolated from normal and diabetic rats as well as tissue radio-conversion of exogenous arachidonic acid, were studied. Vasa deferentia from rats with acute streptozotocin-induced diabetes showed hypersensitivity to exogenous norepinephrine (NE). This increased contractile response was associated with the interaction of the agonist with alpha adrenoceptors. Inhibitors of cyclooxygenase increased and inhibitors of lipoxygenase(s) abolished the enhanced response to NE of diabetic vas deferens. Vasa deferentia from both normal and diabetic rats, converted (1-14C)-arachidonic acid (AA) into PGF, PGE, PGD and thromboxane (TX) B2, but the % of AA metabolites formed was significantly higher in the diabetic than in the normal condition. Moreover, the predominant prostanoid generated by tissue preparations from diabetic animals was PGD2. Taken together the present experimental findings indicate that preparations from rats with acute streptozotocin-induced diabetes have an augmented reactivity towards NE, which appeared associated with changes in metabolites of AA generated via cyclooxygenase and lipoxygenase catalized pathways.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002396:Catechols / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009637:Masoprocol; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000096:biosynthesis; D011457:Prostaglandins D / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014649:Vas Deferens / Q000187:drug effects / Q000503:physiopathology*
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D002396:Catechols; D011453:Prostaglandins; D011457:Prostaglandins D; D010643:Phenoxybenzamine; D016718:Arachidonic Acid; D009637:Masoprocol; D001241:Aspirin; D015230:Prostaglandin D2; D009638:Norepinephrine; D007213:Indomethacin