Matsuda S, Matsunaga K, Ueda M
Nihon Yakurigaku Zasshi. 1982 May;79(5):421-30.
Antihypertensive and related hemodynamic effects of trichlormethiazide (TCM), a thiazide, in DOC/saline hypertensive rats were investigated. To prepare hypertensive rats, 7-week-old male Wistar rats were subjected to nephrectomy of the left kidney, subcutaneously administered DOC (5 mg/kg X 3 times/week, or a 25-mg tablet), and given 1% saline solution as drinking water. When the systolic blood pressure of the rats reached about 200 mmHg, once-a-day oral administration of an arabic gum suspension of TCM was started. The results were: 1) Oral administration of TCM at no less than 3 mg/kg/day showed a dose-dependent, lasting antihypertensive effect throughout the experimental periods. 2) TCM administration effectively prevented the appearance of malignant hypertensive symptoms such as body weight loss, ischemia of the ocular fundus, and slight paralysis of extremities with the following pathological changes: hyalinization and fibrinoid necrosis of renal arteries and glomeruli, degeneration of renal tubules, and cardiac hypertrophy. 3) Although TCM had no effect throughout the experimental periods on the cardiac output (CO), which was determined by a modified dye-dilution method, total peripheral resistance (TPR) decreased from the first week of TCM administration. The antihypertensive effect of TCM in DOC/saline hypertensive rats is presumed to be associated with the decrease of TPR from early stages of therapy.
研究了噻嗪类药物三氯甲噻嗪（TCM）对醋酸脱氧皮质酮（DOC）/生理盐水诱导的高血压大鼠的降压及相关血流动力学效应。为制备高血压大鼠，对7周龄雄性Wistar大鼠进行左肾切除术，皮下注射DOC（5mg/kg，每周3次，或给予一片25mg的片剂），并给予1%盐水作为饮用水。当大鼠收缩压达到约200mmHg时，开始每日一次口服TCM阿拉伯胶悬液。结果如下：1）每日口服TCM不少于3mg/kg在整个实验期间呈现剂量依赖性、持久的降压作用。2）给予TCM有效预防了恶性高血压症状的出现，如体重减轻、眼底缺血和肢体轻度麻痹，并伴有以下病理变化：肾动脉和肾小球的玻璃样变和纤维蛋白样坏死、肾小管变性和心脏肥大。3）尽管在整个实验期间TCM对用改良染料稀释法测定的心输出量（CO）没有影响，但从给予TCM的第一周起总外周阻力（TPR）就降低了。推测TCM对DOC/生理盐水诱导的高血压大鼠的降压作用与治疗早期TPR的降低有关。
