Takanohashi A, Tojo A, Kobayashi N, Yagi S, Matsuoka H
Department of Internal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Jpn Heart J. 1996 Mar;37(2):251-9. doi: 10.1536/ihj.37.251.
Nitric oxide (NO) production is reduced in patients with essential hypertension and in some experimental models. We have investigated the effect of trichlormethiazide and captopril on NO synthase (NOS) activity and glomerular damage in the kidney of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. DOCA-salt rats were induced with weekly injections of DOCA (30 mg/kg body weight (BW) and 1% saline in drinking water after right nephrectomy. As antihypertensive therapies, CAP (captopril, 40 mg/kg BW) and TCM (trichlormethiazide, 10 mg/kg BW) were given after induction of DOCA-salt hypertension. The increased blood pressure was significantly lowered by TCM, but not by CAP after 5 weeks. Nitrite production in kidney slices was suppressed in DOCA-salt rats, and immunoreactivity for both brain-type NOS (B-NOS) in macula densa and endothelial-type NOS (EC-NOS) in renal vessels was decreased. TCM significantly increased the nitrite production in the kidney slices and B-NOS immunoreactivity, whereas these changes were less in CAP. Glomerulosclerosis score was significantly higher in DOCA-salt rats, and TCM ameliorated renal damage more effectively than CAP. These results indicate that the reduced nitrite production in the kidney of DOCA-salt hypertensive rats was increased more effectively by trichlormethiazide than by captopril, via increased immunoreactivity for B-NOS in the macula densa, and prevented renal damage.
原发性高血压患者及一些实验模型中一氧化氮(NO)生成减少。我们研究了三氯噻嗪和卡托普利对醋酸脱氧皮质酮(DOCA)-盐性高血压大鼠肾脏中一氧化氮合酶(NOS)活性及肾小球损伤的影响。DOCA-盐性大鼠通过每周注射DOCA(30毫克/千克体重)并在右肾切除术后饮用1%盐水诱导而成。作为抗高血压疗法,在诱导DOCA-盐性高血压后给予卡托普利(CAP,40毫克/千克体重)和三氯噻嗪(TCM,10毫克/千克体重)。5周后,三氯噻嗪可显著降低升高的血压,但卡托普利无此效果。DOCA-盐性大鼠肾切片中亚硝酸盐生成受到抑制,致密斑中脑型NOS(B-NOS)和肾血管中内皮型NOS(EC-NOS)的免疫反应性均降低。三氯噻嗪可显著增加肾切片中亚硝酸盐生成及B-NOS免疫反应性,而卡托普利的这些变化较小。DOCA-盐性大鼠的肾小球硬化评分显著更高,三氯噻嗪比卡托普利更有效地改善了肾脏损伤。这些结果表明,通过增加致密斑中B-NOS的免疫反应性,三氯噻嗪比卡托普利更有效地增加了DOCA-盐性高血压大鼠肾脏中减少的亚硝酸盐生成,并预防了肾脏损伤。