Beneficial effect of trandolapril on the lifespan of a severe hypertensivemodel

It remains to be clarified whether ACE inhibitors extend the lifespan in ca ses of severe hypertension. In the present study, we examined whether inhib ition of angiotensin-converting enzyme (ACE) would affect mortality in a ve ry severe hypertensive model. Twelve-week-old stroke-prone spontaneously hy pertensive rats (SHR-SP) and Wistar-Kyoto rats (WKY) were used, and measure ments at this age were taken as the basal values. At this age, the systolic blood pressure of SHR-SP was 219 +/- 4 mmHg, while that of WKY was 102 +/- 3 mmHg. After 12 weeks of sodium loading, the systolic blood pressure in t he placebo-treated SHR-SP reached to 251 +/- 4 mmHg. At 4 weeks of sodium l oading, 85% of the placebo-treated SHR-SP had died, and the systolic blood pressure of the surviving rats was 249 +/- 26 mmHg. In the trandolapril-tre ated SHR-SP, the systolic blood pressure was gradually increased to 293 +/- 5 mmHg at 16 weeks, and none of the mice had died at this time point (0% m ortality). The ACE activities of the aorta, brain, heart and kidney were in creased in the surviving placebo-treated SHR-SP at 4 weeks compared with th e basal levels, while they were significantly decreased in the trandolapril -treated SHR-SP at 16 weeks. These data demonstrate that trandolapril exten ds the lifespan of this severe hypertensive model, even in cases in which t he blood pressure cannot be lowered.