Beneficial Effect of Trandolapril on the Lifespan of a Severe Hypertensive Model.

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Abstract
It remains to be clarified whether ACE inhibitors extend the lifespan in cases of severe hypertension. In the present study, we examined whether inhibition of angiotensin-converting enzyme (ACE) would affect mortality in a very severe hypertensive model. Twelve-week-old stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar-Kyoto rats (WKY) were used, and measurements 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 the placebo-treated SHR-SP reached to 251±4 mmHg. At 4 weeks of sodium loading, 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-treated 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% mortality). The ACE activities of the aorta, brain, heart and kidney were increased in the surviving placebo-treated SHR-SP at 4 weeks compared with the basal levels, while they were significantly decreased in the trandolapril-treated SHR-SP at 16 weeks. These data demonstrate that trandolapril extends the lifespan of this severe hypertensive model, even in cases in which the blood pressure cannot be lowered. (Hypertens Res 2001; 24: 559-564)