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)

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 reduction 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. After 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 hypertension development in SHRs seems to be related to its strong and long-lasting ACE inhibition, especially in the vasculature.