Plasma prostaglandin levels and circulating fuel levels in rats with diabetic ketoacidosis: effects of cyclooxygenase inhibitors and of alpha and beta adrenergic blockade.
We studied the effects of two structurally unrelated inhibitors of the fatty acid cyclooxygenase and of alpha and beta adrenergic blockade on the elevated plasma levels of 13,14-dihydro-15-keto-prostaglandin (PG)E2, 6-keto-PGF1 alpha and thromboxane (TX)B2, the stable derivatives of PGE2, PGI2 (prostacyclin) and TXA2, respectively, in rats with streptozotocin-induced diabetic ketoacidosis (DKA). Meclofenamic acid and indomethacin each produced a significant decrease in the elevated plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1 alpha and TXB2. Phentolamine significantly reduced the plasma level of TXB2 but had no effect on the elevated circulating levels of glucose, free fatty acids, total ketones, 13,14-dihydro-15-keto-PGE2 or 6-keto-PGF1 alpha. Propranolol significantly reduced the elevated circulating levels of glucose, free fatty acids and total ketones but had no effect on the levels of the three prostaglandin derivatives. The ability of meclofenamic acid and indomethacin to reduce the plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1 alpha and TXB2 confirms that the plasma levels of these three derivatives are elevated in rats with DKA. Since abnormalities in the production of PGI2 and perhaps other cyclooxygenase derivatives may contribute to the pathogenesis of certain important hemodynamic and gastrointestinal features of DKA, cyclooxygenase inhibitors may play a role in the management of selected patients with this disorder. Alpha adrenergic activity is essential for the maintenance of the elevated plasma TXB2 level in rats with DKA. The fall in the plasma TXB2 level during alpha adrenergic blockade appears to reflect inhibition of platelet aggregation and platelet TXA2 production, but other sources of the elevated plasma TXB2 level in DKA are not excluded. Beta adrenergic activity contributes to the maintenance of elevated circulating levels of glucose, free fatty acids and total ketones in experimental DKA but not to the elevated plasma levels of the prostaglandin derivatives.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016861:Cyclooxygenase Inhibitors; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D016883:Diabetic Ketoacidosis / Q000097:blood*; D015232:Dinoprostone / Q000031:analogs & derivatives*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007213:Indomethacin / Q000494:pharmacology*; D007657:Ketone Bodies / Q000097:blood; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D011453:Prostaglandins / Q000097:blood*; D011458:Prostaglandins E / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D011453:Prostaglandins; D011458:Prostaglandins E; D062367:ortho-Aminobenzoates; C025087:15-keto-13,14-dihydroprostaglandin E2; D008469:Meclofenamic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011433:Propranolol; D015232:Dinoprostone; D007213:Indomethacin; D010646:Phentolamine