Increased renal TXA2 synthesis in diabetes mellitus: simultaneous determination of urinary TXB2 and 2,3-dinor-TXB2.
The present study was designed to determine urinary excretion of kallikrein(KAL)-kinin as well as prostaglandin (PG) E2, TXB2 and 2,3-dinor-TXB2, a major urinary metabolite of TXA2 synthesized in platelets, by specific RIAs in patients with diabetes mellitus (DM). KAL or kinin excretion in 26 type II DM did not differ from control values obtained in 18 age-matched healthy subjects (C), although DM with HbA1 greater than 11% excreted less KAL. Urinary PGE2 excretion (7.6 +/- 2.8 ng/mg creatinine, mean +/- SE) was significantly lower in DM compared to C (17.5 +/- 3.9, p less than 0.05), while DM excreted more TXB2 (0.57 +/- 0.09, p less than 0.01) and 2,3-dinor-TXB2 (0.56 +/- 0.12, N.S.) than C (0.19 +/- 0.02 or 0.33 +/- 0.01). DM with or without mild proteinuria demonstrated lower PGE2, but higher TXB2 and 2,3-dinor-TXB2 excretion. A positive correlation of TXB2/2,3-dinor-TXB2 with proteinuria was observed in this group. However, in DM with massive proteinuria over 500 micrograms/mg creatinine, TXB2 and 2,3-dinor-TXB2 excretion decreased to levels almost identical to C. As a whole, a ratio of TXB2 to PGE2 or 2,3-dinor-TXB2 in DM was significantly higher than in C. The results suggest that a relative preponderance of TXB2 to 2,3-dinor-TXB2 may indicate an augmented renal, in addition to platelet, TXA2 synthesis. An excessive vasoconstrictive and proaggregatory TXA2 renal synthesis, concomitant with a decrease in vasodilatory and antiaggregatory PGE2, may have profound effects on renal functions such as protein excretion in DM.
Katayama
S
S
Fourth Department of Medicine, Saitama Medical School, Japan.
Inaba
M
M
Maruno
Y
Y
Omoto
A
A
Kawazu
S
S
Ishii
J
J
Sawada
M
M
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000652:urine; D015777:Eicosanoids / Q000652:urine; D004950:Esterases / Q000378:metabolism; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D007705:Kinins / Q000652:urine; D008297:Male; D008875:Middle Aged; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
D015777:Eicosanoids; D007705:Kinins; D013929:Thromboxane B2; D013928:Thromboxane A2; C028965:2,3-dinor-thromboxane B2; D004950:Esterases; D007610:Kallikreins; D015232:Dinoprostone