Antihypertensive activity of the angiotensin converting enzyme inhibitor quinapril HCl: (S)-2-[(S)-N-[(S)-1-ethoxycarbonyl-3-phenylpropyl) alanyl-1,2,3,4- tetrahydro-3-isoquinolinecarboxylic acid monohydrochloride in various hypertensive animal models

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.