Increased apoptosis in the heart of genetic hypertension, associated with increased fibroblasts

Objective: The present studies were undertaken to identify apoptosis in car diomyocytes of genetic hypertension and to study the relationship among apo ptosis, aging and blood pressure, and the effect of angiotensin-converting enzyme (ACE) inhibitors on apoptosis. Methods: Apoptosis in the hearts of s pontaneously hypertensive rats (SHR) was identified by electron microscopy (EM) and DNA laddering, and quantified from age 3 weeks to 64 weeks in comp arison with normotensive rats (WKY). Fibroblasts and protein products of Bc l-2 and Bax were measured by quantitative immunohistochemistry. SHR were tr eated with ramipril, an ACE inhibitor. Results: The results showed that: (1 ) ultrastructural characteristics of apoptosis were observed in cardiomyocy tes of SHR, with shrinkage of the cell and condensation of the cytoplasm an d chromatin. A DNA ladder was shown; (2) a significant increase in apoptosi s in SHR began as early as age 4 weeks and reached a plateau at 16 weeks an d maintained at high levels up to 64 weeks. Blood pressure (BP) in SHR star ted to increase significantly at age 5 weeks; (3) fibroblasts were signific antly increased in the heart of SHR; (4) the ratio of Bcl-2/Bax was signifi cantly reduced in SHR; and (6) ramipril effectively reduced apoptosis and f ibroblasts, and increased the ratio of Bcl-2/Bax. Conclusion: Apoptosis occ urs in the cardiomyocytes of genetic hypertension although fibroblasts are increased, and a significant, age-dependent increase in apoptosis is observ ed. The increase in apoptosis occurs before the difference in blood pressur e is detectable. The ACE inhibitor ramipril may be useful for prevention of apoptosis in the heart. (C) 2000 Elsevier Science B.V. All rights reserved .