Protective effect of thromboxane synthetase inhibitor on hypertensive renal damage in Dahl salt-sensitive rats.
1. The effects of OKY-046, a specific thromboxane (TX) synthetase inhibitor, on blood pressure, urinary excretion of TX and its release from blood platelets and renal papilla, and pathological change of glomeruli were evaluated in Dahl salt-sensitive rats. 2. Average daily intakes of OKY-046-treated rats were 0.93 mg/kg (low dose), 9.8 mg/kg (moderate dose), and 88 mg/kg (high dose). 3. Systolic blood pressure tended to decrease by 6.3, 11.4, and 10.9% in three OKY-treated groups. 4. OKY-046 suppressed the release of TX from platelets in a dose-dependent fashion. Both TX in urine and released from renal papilla decreased in OKY-treated groups with moderate and high dose. OKY-046 resulted no change in urinary excretion or release from renal papilla of prostaglandin E2 or 6-keto-prostaglandin F1alpha. 5. Glomerular sclerosis score decreased significantly in both groups treated with moderate and high doses of OKY-046. 6. An inhibition of renal TX synthesis by TX synthetase inhibitor has a protective effect on the development of hypertensive renal damage with minor antihypertensive effect in Dahl salt-sensitive rats.
Gomi
T
T
Department of Nephrology, NTT Kanto Teishin Hospital, Tokyo, Japan.
Ikeda
T
T
Sasaki
Y
Y
Kosugi
T
T
Shibuya
Y
Y
Sakurai
J
J
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008689:Methacrylates / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012598:Sclerosis / Q000473:pathology / Q000517:prevention & control; D012965:Sodium Chloride; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D008689:Methacrylates; D012965:Sodium Chloride; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase; C034364:ozagrel