Tsunoda K, Abe K, Hagino T, Omata K, Misawa S, Imai Y, Yoshinaga K
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Am J Hypertens. 1993 Jan;6(1):28-32. doi: 10.1093/ajh/6.1.28.
We examined the chronic effects of losartan (DuP 753), a novel orally active angiotensin II receptor antagonist, on blood pressure and renal function in eight hospitalized patients with essential hypertension. After a control period of 1 week, losartan was administered orally once a day for 2 to 4 weeks in increasing doses of 12.5, 25, 50, and 100 mg, until blood pressure in the supine position decreased more than 20 mm Hg (systolic) and 10 mm Hg (diastolic) (or 13 mm Hg in mean blood pressure). The average dose of losartan was 59.4 +/- 43.7 (mean +/- SD) mg/day. Systolic, diastolic, and mean blood pressures, according to 24 h monitoring, fell significantly, from 151.9 +/- 6.8 to 137.2 +/- 7.9 mm Hg, from 90.6 +/- 3.7 to 81.0 +/- 3.7 mm Hg, and from 111.1 +/- 4.6 to 99.7 +/- 5.0 mm Hg, respectively (mean +/- SE, P < .01 for each), with no change in circadian rhythm or variability of blood pressure. Reduction in blood pressure was slightly greater during daytime than during sleep time. Unlike peptide angiotensin II antagonists, losartan did not exert pressor action. No significant alterations were observed in body weight, serum electrolytes, creatinine clearance, urine volume, or urinary excretion of sodium. Losartan significantly lowered serum uric acid concentration from 5.5 +/- 0.4 to 4.8 +/- 0.3 mg/dL (P < .05). Urinary excretion of uric acid increased significantly from 498.9 +/- 64.4 to 540.6 +/- 66.6 mg/day (P < .05). Plasma renin activity rose significantly but plasma aldosterone concentration did not change with the losartan treatment. These results suggest that losartan has a long-acting hypotensive effect with a hypouricemic action in essential hypertension.
我们研究了新型口服活性血管紧张素II受体拮抗剂氯沙坦（DuP 753）对8例住院原发性高血压患者血压和肾功能的长期影响。在1周的对照期后，氯沙坦以12.5、25、50和100mg递增剂量每日口服1次，持续2至4周，直至仰卧位血压收缩压下降超过20mmHg、舒张压下降超过10mmHg（或平均血压下降13mmHg）。氯沙坦的平均剂量为59.4±43.7（均值±标准差）mg/天。根据24小时监测，收缩压、舒张压和平均血压显著下降，分别从151.9±6.8降至137.2±7.9mmHg，从90.6±3.7降至81.0±3.7mmHg，从111.1±4.6降至99.7±5.0mmHg（均值±标准误，每项P<.01），血压的昼夜节律或变异性无变化。白天血压下降幅度略大于睡眠时间。与肽类血管紧张素II拮抗剂不同，氯沙坦不产生升压作用。体重、血清电解质、肌酐清除率、尿量或尿钠排泄均未观察到显著变化。氯沙坦使血清尿酸浓度从5.5±0.4显著降至4.8±0.3mg/dL（P<.05）。尿酸尿排泄量从498.9±64.4显著增加至540.6±66.6mg/天（P<.05）。氯沙坦治疗后血浆肾素活性显著升高，但血浆醛固酮浓度未改变。这些结果表明，氯沙坦在原发性高血压中具有长效降压作用和降尿酸作用。
