Beneficial effect of trandolapril on the lifespan of a severe hypertensive model.
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.
Takai
S
S
Department of Pharmacology, Osaka Medical College, Takatsuki, Japan. pha010@art.osaka-med.ac.jp
Sakonjo
H
H
Miyazaki
M
M
D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000201:enzymology; D001794:Blood Pressure; D001835:Body Weight; D001921:Brain / Q000201:enzymology; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality*; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D016019:Survival Analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; C052035:trandolapril; D007703:Peptidyl-Dipeptidase A