Effects of Y-27152, a new K channel opener with gradual onset of action and less tachycardia, on the development of hypertension and cardiac hypertrophy in Dahl salt-sensitive rats

• Published in: Japanese Journal of Pharmacology 1992, Vol.58 (suppl.2), p.393-393
• Main Authors: Kiminori Kawahara, Yohji Miura
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

There have been few studies showing the effectiveness of K channel openers against left ventricular hypertrophy (LVH) associated with hypertension despite their antihy-pertensive action in laboratory animals. In the present study, we examined the effects of Y-27152 on LVH and hypertension development (HD) in Dahl salt-sensitive (S) rats. Six-week-old female S rats were given 8 or 0.1% NaCl diet for 5 weeks. Vehicle (2 ml/kg), Y-27152(0.25-1 mg/kg) or lemakalim (1 mg/kg) was orally administered once daily from 1 to 5 weeks on 8% NaCl diet. Systolic blood pressure (BP) was measured once a week by tail cuff method before drug administration. After 4 weeks dosing, the heart was excised under pentobarbital anesthesia and the wet LV weight was measured. In vehicle groups, S rats on 8% NaCl diet for 5 weeks developed hypertension and LVH which was indicated by the heavy LV mass compared with S rats given 0.1% NaCl diet. Y-27152 dose-dependently suppressed HD and LVH. In contrast, lemakalim did not modify LV mass in spite of the same degree of attenuation of HD as Y-27152 (0.25 mg/kg). Suppression of LVH by Y-27152 primarily may result from lowering of BP. The reason why lemakalim failed to prevent LVH is unknown but may partly be due to the extreme reflex activation of neurohumoral system which blunts an antitrophic effect of BP reduction. Y-27152 may be expected to suppress LVH in hypertensive patients.