BENEFICIAL EFFECT OF A NOVEL DIURETIC, M17055, ON BLOOD-PRESSURE AND CARDIOVASCULAR HYPERTROPHY IN SPONTANEOUSLY HYPERTENSIVE RATS

We investigated the effects of a novel diuretic, M17055, on blood pres sure and cardiovascular hypertrophy in spontaneously hypertensive rats (SHR). M17055 was orally administered once a day for 24 consecutive d ays 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 we ight 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-depend ent manner. The effect of M17055 on cardiac hypertrophy was more poten t (P < 0.01) than that of captopril, when the comparison was performed at the doses of M17055 and captopril inducing the same extent of bloo d-pressure decrement. Vascular hypertrophy was evaluated by the media/ lumen ratio (M/L) in the thoracic aorta and the first branch of the su perior mesenteric artery. In the aorta, M/L was slightly, but not sign ificantly, decreased by M17055 at doses of 2.5 and 5 mg/kg/day, wherea s it was decreased significantly (P < 0.01) by captopril. In the mesen teric 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.