[Investigation of inhibitory effect of ramipril on apoptosis in spontaneously hypertensive rats].
To explore the effect of angiotensin converting enzyme (ACE) inhibitor on apoptosis in spontaneously hypertensive rats(SHR), and normotensive control rats (WKY) at different ages were used. Ramipril (1 mg.kg-1.d-1) was administered orally to male SHR from 3 or 5 weeks to 10 weeks of age. Male and age-matched untreated SHR and WKY were used as controls. Experiments determined. 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. The results of the 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 age 4 weeks and continued to increase up to a plateau at age 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 ACE, the DNA fragmentation, like BP and HW/BW, was reduced significantly (70.7%) as compared with that of untreated SHR(P < 0.01); and similar to that of the WKY (P > 0.1), the DNA ladder disappeared, which was very obvious in the untreated SHR. These studies demonstrate that ramipril can prevent the development of hypertension and myocardial hypertrophy and can inhibit the increase in the apoptosis of SHR cardiac myocytes, suggesting that apoptosis may be involved in the pathogenesis of genetic hypertension.
Peng
L
L
Department of Laboratory Medicine, First Affiliated Hospital, WCUMS, Chengdu 610041.
Bradeley
C
C
Liu
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / 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