Shinkawa T, Kato Y, Tsuchiya N, Yamasaki F, Uemura A, Mizota M
Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
Jpn J Pharmacol. 1993 Oct;63(2):241-9. doi: 10.1254/jjp.63.241.
We investigated the effects of a novel diuretic, M17055, on blood pressure and cardiovascular hypertrophy in spontaneously hypertensive rats (SHR). M17055 was orally administered once a day for 24 consecutive days to 14-week-old male SHR. M17055 at doses of 1.25, 2.5 and 5 mg/kg/day exerted a dose-related diuretic and antihypertensive effect during the treatment. The weight of the left ventricle normalized by body weight on the following day of the last dosage was significantly (P < 0.01) reduced by M17055 at doses of 2.5 and 5 mg/kg/day in a dose-dependent manner. The effect of M17055 on cardiac hypertrophy was more potent (P < 0.01) than that of captopril, when the comparison was performed at the doses of M17055 and captopril inducing the same extent of blood-pressure decrement. Vascular hypertrophy was evaluated by the media/lumen ratio (M/L) in the thoracic aorta and the first branch of the superior mesenteric artery. In the aorta, M/L was slightly, but not significantly, decreased by M17055 at doses of 2.5 and 5 mg/kg/day, whereas it was decreased significantly (P < 0.01) by captopril. In the mesenteric artery, the ratio was significantly (P < 0.05) reduced by M17055 at a dose of 5 mg/kg/day. These results suggest that M17055 possesses beneficial properties for the clinical treatment of hypertension.
我们研究了新型利尿剂M17055对自发性高血压大鼠（SHR）血压和心血管肥大的影响。将14周龄雄性SHR连续24天每天口服一次M17055。在治疗期间，剂量为1.25、2.5和5mg/kg/天的M17055发挥了剂量相关的利尿和降压作用。末次给药次日，剂量为2.5和5mg/kg/天的M17055以剂量依赖性方式显著（P<0.01）降低了以体重标准化的左心室重量。当在诱导相同程度血压下降的M17055和卡托普利剂量下进行比较时，M17055对心脏肥大的作用比卡托普利更强（P<0.01）。通过胸主动脉和肠系膜上动脉第一分支的中膜/管腔比（M/L）评估血管肥大。在主动脉中，剂量为2.5和5mg/kg/天的M17055使M/L略有降低，但无显著差异，而卡托普利则使其显著降低（P<0.01）。在肠系膜动脉中，剂量为5mg/kg/天的M17055使该比值显著降低（P<0.05）。这些结果表明，M17055对高血压的临床治疗具有有益特性。
