A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic nephropathy.
Spontaneously hypertensive rats (SHR) were injected with streptozotocin (STZ-SHR) to induce diabetes. The effect of DP-1904, a thromboxane A2 synthetase inhibitor, on diabetic nephropathy was then studied by administering it for 5 months (1 or 10 mg/kg). DP-1904 did not affect renal 6-keto prostaglandin (PG)F1 alpha production in STZ-SHR, but markedly inhibited renal thromboxane (TX) B2 production, so that the 6-keto PGF1 alpha/TXB2 ratio was significantly increased (P less than 0.05). STZ-SHR showed significant uraemia and proteinuria, plus increases in urinary gamma-glutamyl-transpeptidase and urinary N-acetyl-beta-glucosaminidase. DP-1904 significantly decreased (P less than 0.01) the urinary changes. STZ-SHR also showed an increase in mesangial periodic acid-Schiff-positive substance and in relative renal weight, both of which were significantly inhibited by DP-1904 (P less than 0.05). Thus, DP-1904 inhibited both TXB2 production and the progression of renal damage in STZ-SHR.
Department of Pharmacology, Kagawa Medical School, Japan.
H
H
Masumura
S
S
Kunitada
K
K
Irie
S
S
Ashida
Y
Y
Abe
D000118:Acetylglucosaminidase / Q000187:drug effects / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000150:complications* / Q000235:genetics; D007093:Imidazoles / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011453:Prostaglandins / Q000378:metabolism; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D005723:gamma-Glutamyltransferase / Q000187:drug effects / Q000652:urine
D007093:Imidazoles; D011453:Prostaglandins; D013764:Tetrahydronaphthalenes; D013929:Thromboxane B2; C056295:nafagrel; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D013930:Thromboxane-A Synthase