Yaoka O, Aoki K, Nakajima T, Setoguchi M
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Nihon Yakurigaku Zasshi. 1993 Jul;102(1):35-45. doi: 10.1254/fpj.102.35.
The antihypertensive activity of quinapril was examined in normotensive and various hypertensive animal models. In 2-kidney, 1-clip renal hypertensive rats (2K-RHR), quinapril (0.1 to 1.0 mg/kg, p.o.) had a dose-related and sustained antihypertensive action, which was as potent as that of enalapril and approximately 40 times stronger than that of captopril. Heart rate was not changed by these doses of quinapril. In spontaneously hypertensive rats (SHR) and 1-kidney, 1-clip renal hypertensive rats, quinapril as well as enalapril dose-dependently produced a significant fall in blood pressure. The relative potency and duration of the effect of quinapril was the same as that of enalapril in these models. Quinapril at 30 mg/kg, p.o. lowered blood pressure and increased heart rate in normotensive rats. In contrast, quinapril and enalapril failed to reduce blood pressure in DOCA/salt hypertensive rats. In the repeated dose study, no development of tolerance was observed during the administration period in 2K RHR and SHR. The antihypertensive effects in 2K RHR was greater than those in SHR. Quinapril was more potent and long-lasting than enalapril in 2K RHR and SHR. From these results, quinapril is expected to be useful for the clinical treatment of hypertension.
在正常血压和各种高血压动物模型中研究了喹那普利的降压活性。在两肾一夹肾性高血压大鼠(2K-RHR)中,喹那普利(0.1至1.0毫克/千克,口服)具有剂量相关的持续降压作用,其效力与依那普利相当,比卡托普利强约40倍。这些剂量的喹那普利不会改变心率。在自发性高血压大鼠(SHR)和一肾一夹肾性高血压大鼠中,喹那普利以及依那普利均剂量依赖性地使血压显著下降。在这些模型中,喹那普利作用的相对效力和持续时间与依那普利相同。口服30毫克/千克的喹那普利可降低正常血压大鼠的血压并增加心率。相比之下,喹那普利和依那普利未能降低DOCA/盐性高血压大鼠的血压。在重复给药研究中,在2K RHR和SHR的给药期间未观察到耐受性的产生。2K RHR中的降压作用大于SHR中的降压作用。在2K RHR和SHR中,喹那普利比依那普利更有效且作用更持久。从这些结果来看,喹那普利有望用于高血压的临床治疗。