Richer C, Doussau M P, Giudicelli J F
Arch Mal Coeur Vaiss. 1982 Jun;75 Spec No:55-8.
MK 421, 25 mg/kg, administered daily by gavage to young spontaneously hypertensive rats (SHRs) from their 4th to 15th weeks of age almost completely inhibited genetic hypertension development. Since heart rate and cardiac index were not drug affected, prevention of genetic hypertension development was solely related to an early, potent and long-lasting limitation of the progressive increase in peripheral resistance which normally develops in SHRs during ageing. MK 421 slightly enhanced vascular responsiveness to exogenous norepinephrine and angiotensin II and reduced myocardial hypertrophy. Plasma renin concentration was increased. MK 421 slightly reduced body growth but did not affect fluid intake, urinary volume and urinary ADH, demonstrating that no water or salt retention developed. Finally, MK 421's preventive effects against genetic hypertension development persisted up to 10 weeks after treatment discontinuation.
MK 421，25毫克/千克，从第4周龄至15周龄每天经口灌胃给予幼年自发性高血压大鼠（SHR），几乎完全抑制遗传性高血压的发展。由于心率和心脏指数不受药物影响，遗传性高血压发展的预防仅与外周阻力的渐进性增加的早期、强效和持久限制有关，外周阻力的渐进性增加通常在SHR衰老过程中出现。MK 421略微增强了血管对外源性去甲肾上腺素和血管紧张素II的反应性，并减轻了心肌肥大。血浆肾素浓度升高。MK 421略微降低了身体生长，但不影响液体摄入量、尿量和尿抗利尿激素，表明没有发生水或盐潴留。最后，MK 421对遗传性高血压发展的预防作用在停药后持续长达10周。
