Contribution of platelet thromboxane production to enhanced urinary excretion and glomerular production of thromboxane and to the pathogenesis of albuminuria in the streptozotocin-diabetic rat.
Previous studies have demonstrated that urinary thromboxane B2 (TXB2) excretion (UTXB2) and glomerular production of TXB2 are enhanced in experimental diabetes and that selective inhibitors of TX synthesis prevent or delay the development of albuminuria. The present study was conducted to examine the contribution of platelet TXB2 production to the enhancement of UTXB2 and glomerular TXB2 production and to the pathogenesis of albuminuria in the partially insulin-treated moderately hyperglycemic (blood glucose, 200 to 400 mg/dL) streptozotocin-diabetic rat (SDR). Treatment of control rats or of SDR with diabetes of 5 months' duration with antiplatelet serum for 4 consecutive days reduced circulating platelet counts and serum TXB2 generation, an index of platelet cyclooxygenase activity, by 80% or greater, but reduced UTXB2 excretion by only 30%. UTXB2 and glomerular production of TXB2 of thrombocytopenic SDR remained markedly elevated compared with corresponding values from age-matched thrombocytopenic or platelet-replete, nondiabetic controls. Similarly, treatment of rats for 180 days with a dose of aspirin (ASA), which selectively inhibited platelet versus renal cyclooxygenase activity, reduced UTXB2 of both SDR and controls by 25% to 35%. The absolute reductions in UTXB2 induced by either ASA or thrombocytopenia in SDR were significantly greater than the absolute decrements in corresponding controls, suggesting that increased platelet TXB2 production in SDR may contribute to the enhanced UTXB2. However, as in the thrombocytopenic SDR, UTXB2 and glomerular production of TXB2 of SDR treated with ASA remained clearly above corresponding control values. Moreover, chronic ASA treatment failed to prevent the development of albuminuria in SDR.(ABSTRACT TRUNCATED AT 250 WORDS)
DeRubertis
F R
FR
Department of Medicine, University of Pittsburgh, PA.
Craven
P A
PA
D000419:Albuminuria / Q000209:etiology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005919:Glomerular Filtration Rate; D007678:Kidney Glomerulus / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013921:Thrombocytopenia / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis* / Q000652:urine
D013929:Thromboxane B2; D015232:Dinoprostone; D001241:Aspirin