Increased apoptosis in the heart of genetic hypertension, associated with increased fibroblasts.
OBJECTIVE
The present studies were undertaken to identify apoptosis in cardiomyocytes of genetic hypertension and to study the relationship among apoptosis, aging and blood pressure, and the effect of angiotensin-converting enzyme (ACE) inhibitors on apoptosis.


METHODS
Apoptosis in the hearts of spontaneously hypertensive rats (SHR) was identified by electron microscopy (EM) and DNA laddering, and quantified from age 3 weeks to 64 weeks in comparison with normotensive rats (WKY). Fibroblasts and protein products of Bcl-2 and Bax were measured by quantitative immunohistochemistry. SHR were treated with ramipril, an ACE inhibitor.


RESULTS
The results showed that: (1) ultrastructural characteristics of apoptosis were observed in cardiomyocytes of SHR, with shrinkage of the cell and condensation of the cytoplasm and chromatin. A DNA ladder was shown; (2) a significant increase in apoptosis in SHR began as early as age 4 weeks and reached a plateau at 16 weeks and maintained at high levels up to 64 weeks. Blood pressure (BP) in SHR started to increase significantly at age 5 weeks; (3) fibroblasts were significantly increased in the heart of SHR; (4) the ratio of Bcl-2/Bax was significantly reduced in SHR; and (6) ramipril effectively reduced apoptosis and fibroblasts, and increased the ratio of Bcl-2/Bax.


CONCLUSIONS
Apoptosis occurs in the cardiomyocytes of genetic hypertension although fibroblasts are increased, and a significant, age-dependent increase in apoptosis is observed. The increase in apoptosis occurs before the difference in blood pressure is detectable. The ACE inhibitor ramipril may be useful for prevention of apoptosis in the heart.
Liu
J J
JJ
Cardiovascular Biology Unit, Austin Hospital, University of Melbourne, Heidelberg, Victoria, Australia. jjliu@austin.unimelb.edu.au
Peng
L
L
Bradley
C J
CJ
Zulli
A
A
Shen
J
J
Buxton
B F
BF
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053938:DNA Fragmentation; D005347:Fibroblasts / Q000473:pathology; D006321:Heart / Q000503:physiopathology*; D006973:Hypertension / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017257:Ramipril / Q000627:therapeutic use; D051381:Rats; D011921:Rats, Inbred WKY; D051028:bcl-2-Associated X Protein
D000806:Angiotensin-Converting Enzyme Inhibitors; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D017257:Ramipril