Increased thromboxane B2 excretion in diabetes mellitus.
Thromboxane (TX) A2 is a potent vasoconstrictor as well as a proaggregator of platelets. Augmented TXB2 platelet synthesis and attenuated vascular prostacyclin formation have been demonstrated in diabetes mellitus. We undertook to establish a simple method of extracting urinary TXB2 (UTXB2) and to elucidate the pathophysiologic role of renal TXA2 in diabetes mellitus. One-step extraction of UTXB2 with an octadecylsilyl-silica column was sufficient as pretreatment for TXB2 radioimmunoassay because recovery of UTXB2 was good, the eluate was parallel with the dose-response curve, and the value coincided with that obtained by the conventional method. When platelet TXA2 synthesis was completely suppressed by administration of 100 mg aspirin, urinary TXB2 excretion (UTXB2V) declined to 41% of the initial levels, suggesting that renal TXA2 formation contributes significantly to UTXB2V. UTXB2V was 94.5 +/- 14.0 ng/day or 108.8 +/- 17.3 ng/gm creatinine in controls. Approximately half of the patients with diabetes demonstrated a UTXB2 level higher than the mean + 2 SD level of controls. Although UTXB2V did not show a significant correlation with protein excretion, UTXB2V in patients with diabetes with proteinuria greater than 100 mg/day was augmented (224.4 +/- 30.5 ng/day) compared with that in patients with diabetes without proteinuria greater than 100 mg/day. Furthermore, UTXB2V correlated negatively with the p-aminohippuric acid clearance rate, but not with the creatinine clearance rate. The results suggest that renal TXA2 synthesis may be augmented in diabetic nephropathy and may play a pathophysiologic role in renal hemodynamics as well as in protein excretion.
D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D010974:Platelet Aggregation; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000502:physiology*; D013929:Thromboxane B2 / Q000302:isolation & purification / Q000652:urine*; D010130:p-Aminohippuric Acid / Q000652:urine
D013929:Thromboxane B2; D013928:Thromboxane A2; D001241:Aspirin; D010130:p-Aminohippuric Acid