The relationship between apoptosis and spontaneous hypertension.
OBJECTIVE
To explore the relationship between apoptosis and spontaneous hypertension, 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 with 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 cardiomyocytes 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 analysis of DNA fragments.


RESULTS
The results of a quantitative method showed an age-dependent increase in apoptosis in the cardiac tissues of SHR. A significant increase in DNA breaks occurred as early as 4 weeks and continued to increase up to a plateau at 16 weeks in the cardiac tissue of SHR whereas there was no significant change in apoptosis in WKY up to 64 weeks. Moreover, after the treatment 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 untreated SHR (P < 0.01), and similar to that of the control WKY.


CONCLUSIONS
There is a significant increase in the apoptosis of SHR cardiac tissues with increasing age, and ramipril can significantly prevent the increase of apoptosis and in blood pressure, which demonstrates that apoptosis may be involved in the pathogenesis of genetic hypertension. The inhibition of apoptosis as well as hypertension by ACE inhibitors may open a new avenue for developing therapeutic approach for hypertension.
Peng
L
L
Department of Laboratory Medicine, First University Hospital, West China University of Medical Sciences, Chengdu 610041, China. penglim@cdisn.cd.sc.cn
Bradley
C J
CJ
Zulli
A
A
Liu
J J
JJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006973:Hypertension / Q000209:etiology / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril