The relationship between apoptosis and spontaneous hypertension

Objective To explore the relationship between apoptosis and spontaneous hyp ertension, and the effect of; angiotensin converting enzyme (ACE) inhibitor on apoptosis. Methods Male spontaneously hypertensive rats (SHR) and normotensive control rats (WKY) at different ages were used, meanwhile, the treatment of SHR wi th ramipril, an inhibitor of ACE was administered orally (1 mg . kg(-1) . d (-1)) to SHR from 3 to 10 or from 5 to 10 weeks of age. Apoptosis in cardio myocytes of SHR was quantified by a maximal labeling (Lmax) method and the characteristic features of apoptosis were identified by electron microscopy (EM), in situ labeling of DNA strand breaks with terminal deoxynucleotidyl transferase mediated dUTP end labeling (TUNEL) and autoradiographic analys is of DNA fragments. Results The results of a quantitative method showed an age-dependent increa se in apoptosis in the cardiac tissues of SHR. A significant increase in DN A breaks occurred as early as 4 weeks and continued to increase up to a pla teau at 16 weeks in the cardiac tissue of SHR whereas there was no signific ant change in apoptosis in WKY up to 64 weeks. Moreover, after the treatmen t of SHR with ramipril, an inhibitor of angiotensin converting enzyme (ACE) , from 3 to 10 or from 5 to 10 weeks of age, the DNA fragmentation as well as blood pressure (BP) was reduced significantly compared with that of untr eated SHR (P<0.01), and similar to that of the control WKY. Conclusion There is a significant increase in the apoptosis of SHR cardiac tissues with increasing age, and ramipril can significantly prevent the inc rease of apoptosis and in blood pressure, which demonstrates that apoptosis may be involved in the pathogenesis of genetic hypertension. The inhibitio n of apoptosis as well as hypertension by ACE inhibitors may open a new ave nue for developing therapeutic approach for hypertension.