A thromboxane A2 synthase inhibitor, DP-1904, prevents rat renal injury.
The effects of DP-1904, a thromboxane (TX) A2 synthase inhibitor, on renal function were investigated by analysis of prostanoid metabolism in hydronephrotic and ischemic rat kidney models, and in isolated perfused normal and hydronephrotic rat kidneys. The increase in production of TXB2 in hydronephrotic or ischemic kidneys was significantly suppressed by intraperitoneal DP-1904 (10 mg/kg), with the 6-keto-prostaglandin F1 alpha to TXB2 ratio being significant increased. Urine volume, glomerular filtration rate and renal plasma flow were all improved. DP-1904 (0.3 micrograms/min) blocked the effects of infused arachidonic acid on isolated perfused normal rat kidneys thus reducing TXB2 levels and perfusion pressure but the pressor response to norepinephrine or angiotensin II remained unchanged. In isolated perfused hydronephrotic rat kidneys, DP-1904 suppressed the increase in perfusion pressure and TXB2 production caused by platelet-activating factor. These findings suggested that DP-1904 improved renal failure by specifically inhibiting TXA2 production.
Masumura
H
H
Department of Pharmacology, Kagawa Medical School, Japan.
Kunitada
S
S
Irie
K
K
Ashida
S
S
Abe
Y
Y
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D006869:Hydronephrosis / Q000188:drug therapy / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000502:physiology; D013929:Thromboxane B2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D013764:Tetrahydronaphthalenes; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C056295:nafagrel; D013930:Thromboxane-A Synthase