Renal functional abnormalities, occurring before overt renal disease and possibly due to abnormal vascular control mechanisms, have been described in diabetes mellitus. We used intravenous (i.v.) furosemide, which stimulates renal prostaglandin (PG) synthesis and renin release, to compare these vasoactive systems in 14 diabetic and 23 normal control subjects. Using urine thromboxane B2 (TXB2) as an index of renal synthesis of the vasoconstrictor prostanoid TXA2, and urine 6keto-PGF for the vasodilator PGI2, we found evidence of increased renal TXA2 synthesis in diabetic subjects in response to furosemide. The increased TXA2 synthesis did not occur at the expense of PGI2 synthesis, as urine 6keto-PGF was not reduced. Increased TXB2 excretion in diabetic subjects was particularly marked in the first 10 min after i.v. furosemide. During this time, diabetic males excreted 31 ± 6 ng of TXB2 compared with 10 ± 1 ng for normal males (P < 0.05), while diabetic females excreted 15 ± 3 ng compared with 7 ± 1 ng for normal females (P < 0.05). Also, 6keto-PGF excretion at 10 min was increased in diabetic subjects: males, 29 ± 3 ng versus 19 ± 3 (P < 0.05); females, 33 ± 8 versus 16 ± 3 (P < 0.05). The ratio of TXB2 to 6keto-PGF tended to be higher in diabetic males. Plasma renin activity 10 min after i.v. furosemide was lower in diabetic males: 0.9 ± 0.2 ng · ml−1 · h−1 versus 3.5 ± 0.4 (P < 0.05) and tended to be lower in diabetic females: 1.5 ± 0.3 versus 2.0 ± 0.3. There was a significant negative correlation between the TXB2/6keto-PGF ratio and PRA at this time (r = −0.392, P < 0.05), suggesting that the relatively increased TXA2 could be a factor in the reduced early increment in plasma renin activity after i.v. furosemide.

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