血栓素合成酶抑制剂对 Dahl 盐敏感大鼠高血压肾损伤的保护作用。

Protective effect of thromboxane synthetase inhibitor on hypertensive renal damage in Dahl salt-sensitive rats.

Gomi T, Ikeda T, Sasaki Y, Kosugi T, Shibuya Y, Sakurai J

Department of Nephrology, NTT Kanto Teishin Hospital, Tokyo, Japan.

Clin Exp Pharmacol Physiol Suppl. 1995 Dec;22(1):S371-3. doi: 10.1111/j.1440-1681.1995.tb02959.x.

Abstract

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.

摘要

在 Dahl 盐敏感大鼠中评估了特异性血栓素（TX）合成酶抑制剂 OKY - 046 对血压、TX 的尿排泄及其从血小板和肾乳头的释放以及肾小球病理变化的影响。2. OKY - 046 处理组大鼠的平均每日摄入量分别为 0.93 毫克/千克（低剂量）、9.8 毫克/千克（中等剂量）和 88 毫克/千克（高剂量）。3. 三个 OKY 处理组的收缩压分别有降低 6.3%、11.4%和 10.9%的趋势。4. OKY - 046 以剂量依赖性方式抑制血小板 TX 的释放。中等剂量和高剂量 OKY 处理组的尿 TX 及从肾乳头释放的 TX 均减少。OKY - 046 对前列腺素 E2 或 6 - 酮 - 前列腺素 F1α 的尿排泄或从肾乳头的释放无影响。5. 中等剂量和高剂量 OKY - 046 处理组的肾小球硬化评分均显著降低。6. 在 Dahl 盐敏感大鼠中，TX 合成酶抑制剂抑制肾脏 TX 合成对高血压肾损伤的发展具有保护作用，且降压作用较小。