Pharmacological Studies on TA-6366, a New ACE Inhibitor: II. Effect of Long-Term Administration from the Pre-Hypertensive Stage on Blood Pressure, Relative Heart Weight and ACE Activity of Various Tissues in Spontaneously Hypertensive Rats(SHRs).

Abstract

ABSTRACT-The long-term oral administration of TA-6366 (5 mg/kg/day) from 4 weeks old impeded the genetic hypertension development with only a slight decrease in heart rate in spontaneously hypertensive rats (SHRs). However, the lower dose (1 mg/kg/day) of TA-6366 did not affect the development, but it lowered blood pressure after the development was almost accomplished. Concomitantly, relative heart weights in both the groups were markedly decreased to almost the same degree. The reduc tion of ACE activity in the aorta, brain and lung of both groups was found at 24 hr after the final administration, particularly at the 5 mg/kg/day dose; and that of the aorta was kept at almost the same low level even on the 9th day after withdrawal. Af ter withdrawal of TA-6366 (5 mg/kg/day), the significant decrease in blood pressure was sustained at least for 10 weeks. The beneficial effect of TA-6366 on the hyperten sion development in SHRs seems to be related to its strong and long-lasting ACE in hibition, especially in the vasculature.

Effects of Imidapril on Left Ventricular Mass in Chronic Hemodialysis Patients

“…Therefore, in order to prevent cardiovascular organ injuries effectively, it may be important to suppress the cardiovascular tissue RAAS rather than lowering plasma angiotensin II or aldosterone levels (42). In this respect, imidapril has been shown to inhibit ACE activity not only in circulating blood but also in cardiovascular tissues more potently than other ACE inhibitors such as captopril and enalapril (43). We speculate that tissue RAAS inhibition participated in the mechanism of LVM reduction by chronic imidapril treatment in the hemodialysis patients of this study.…”

Altered Prostaglandin Metabolism Induced by Angiotensin-Converting Enzyme Inhibitors in Broncho-Alveolar Lavage Fluid of the Guinea Pig

“…Imidapril, (4S)-1-methyl-3-{(2S)-2[N-(1S)-1-ethoxycarbonyl-3-phenylpropyl)amino]propionyl}-2-oxoimidazolidine-4-carboxylic acid hydrochloride, belongs to a new class of N-carboxyalkyl dipeptide ACE inhibitors (17,18). The antihypertensive effect of imidapril in the spontaneously hypertensive rat was comparable to that of enalapril, and about 4 times that of captopril.…”

“…The antihypertensive effect of imidapril in the spontaneously hypertensive rat was comparable to that of enalapril, and about 4 times that of captopril. Furthermore, imidapril has a long-lasting antihypertensive effect as compared with enalapril and captopril (18,19). In clinical studies in Japan (19) and Europe, imidapril caused coughing only in about 0.9010 of patients.…”