Abstract
We previously reported that chronic inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) induces vascular inflammation at week 1 and produces subsequent arteriosclerosis at week 4 and that cotreatment with an angiotensin-converting enzyme (ACE) inhibitor prevents such changes. In the present study, we tested the hypothesis that treatment with an ACE inhibitor after development of vascular inflammation could inhibit arteriosclerosis in rats. Wistar-Kyoto rats were randomized to four groups: the control group received no drugs, the 4WL-NAME group received L-NAME (100 mg·kg-1·day-1) for 4 wk, the 1wL + 3wNT group received L-NAME for 1 wk and no treatment for the subsequent 3 wk, and the 1wL + 3wACEI group received L-NAME for 1 wk and the ACE inhibitor imidapril (20 mg·kg -1· day-1) for the subsequent 3 wk. After 4 wk, we observed significant arteriosclerosis of the coronary artery (medial thickening and fibrosis) and increased cardiac ACE activity in the 1wL + 3wNT group as well as in the 4WL-NAME group, but not in the 1wL + 3wACEI group. In a separate study, we examined apoptosis formation and found that posttreatment with imidapril (20 mg·kg-1·day-1) or an ANG II AT1-receptor antagonist, CS-866 (5 mg·kg-1·day-1), induced apoptosis (TdT-mediated nick end-labeling) in monocytes and myofibroblasts appearing in the inflammatory lesions associated with a clear degradation in the heart (DNA electrophoresis). In conclusion, treatment with the ACE inhibitor after 1 wk of L-NAME administration inhibited arteriosclerosis by inducing apoptosis in the cells with inflammatory lesions in this study, suggesting that increased ANG II activity inhibited apoptosis of the cells with inflammatory lesions and thus contributed to the development of arteriosclerosis.
| Original language | English |
|---|---|
| Pages (from-to) | H2306-H2312 |
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 280 |
| Issue number | 5 49-5 |
| Publication status | Published - May 1 2001 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Regression by ACE inhibition of arteriosclerotic changes induced by chronic blockade of NO synthesis in rats. / Katoh, Makoto; Egashira, Kensuke; Kataoka, Chu; Usui, Makoto; Koyanagi, Masamichi; Kitamoto, Shiro; Ohmachi, Yasushi; Takeshita, Akira; Narita, Hiroshi.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 280, No. 5 49-5, 01.05.2001, p. H2306-H2312.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regression by ACE inhibition of arteriosclerotic changes induced by chronic blockade of NO synthesis in rats
AU - Katoh, Makoto
AU - Egashira, Kensuke
AU - Kataoka, Chu
AU - Usui, Makoto
AU - Koyanagi, Masamichi
AU - Kitamoto, Shiro
AU - Ohmachi, Yasushi
AU - Takeshita, Akira
AU - Narita, Hiroshi
PY - 2001/5/1
Y1 - 2001/5/1
N2 - We previously reported that chronic inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) induces vascular inflammation at week 1 and produces subsequent arteriosclerosis at week 4 and that cotreatment with an angiotensin-converting enzyme (ACE) inhibitor prevents such changes. In the present study, we tested the hypothesis that treatment with an ACE inhibitor after development of vascular inflammation could inhibit arteriosclerosis in rats. Wistar-Kyoto rats were randomized to four groups: the control group received no drugs, the 4WL-NAME group received L-NAME (100 mg·kg-1·day-1) for 4 wk, the 1wL + 3wNT group received L-NAME for 1 wk and no treatment for the subsequent 3 wk, and the 1wL + 3wACEI group received L-NAME for 1 wk and the ACE inhibitor imidapril (20 mg·kg -1· day-1) for the subsequent 3 wk. After 4 wk, we observed significant arteriosclerosis of the coronary artery (medial thickening and fibrosis) and increased cardiac ACE activity in the 1wL + 3wNT group as well as in the 4WL-NAME group, but not in the 1wL + 3wACEI group. In a separate study, we examined apoptosis formation and found that posttreatment with imidapril (20 mg·kg-1·day-1) or an ANG II AT1-receptor antagonist, CS-866 (5 mg·kg-1·day-1), induced apoptosis (TdT-mediated nick end-labeling) in monocytes and myofibroblasts appearing in the inflammatory lesions associated with a clear degradation in the heart (DNA electrophoresis). In conclusion, treatment with the ACE inhibitor after 1 wk of L-NAME administration inhibited arteriosclerosis by inducing apoptosis in the cells with inflammatory lesions in this study, suggesting that increased ANG II activity inhibited apoptosis of the cells with inflammatory lesions and thus contributed to the development of arteriosclerosis.
AB - We previously reported that chronic inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) induces vascular inflammation at week 1 and produces subsequent arteriosclerosis at week 4 and that cotreatment with an angiotensin-converting enzyme (ACE) inhibitor prevents such changes. In the present study, we tested the hypothesis that treatment with an ACE inhibitor after development of vascular inflammation could inhibit arteriosclerosis in rats. Wistar-Kyoto rats were randomized to four groups: the control group received no drugs, the 4WL-NAME group received L-NAME (100 mg·kg-1·day-1) for 4 wk, the 1wL + 3wNT group received L-NAME for 1 wk and no treatment for the subsequent 3 wk, and the 1wL + 3wACEI group received L-NAME for 1 wk and the ACE inhibitor imidapril (20 mg·kg -1· day-1) for the subsequent 3 wk. After 4 wk, we observed significant arteriosclerosis of the coronary artery (medial thickening and fibrosis) and increased cardiac ACE activity in the 1wL + 3wNT group as well as in the 4WL-NAME group, but not in the 1wL + 3wACEI group. In a separate study, we examined apoptosis formation and found that posttreatment with imidapril (20 mg·kg-1·day-1) or an ANG II AT1-receptor antagonist, CS-866 (5 mg·kg-1·day-1), induced apoptosis (TdT-mediated nick end-labeling) in monocytes and myofibroblasts appearing in the inflammatory lesions associated with a clear degradation in the heart (DNA electrophoresis). In conclusion, treatment with the ACE inhibitor after 1 wk of L-NAME administration inhibited arteriosclerosis by inducing apoptosis in the cells with inflammatory lesions in this study, suggesting that increased ANG II activity inhibited apoptosis of the cells with inflammatory lesions and thus contributed to the development of arteriosclerosis.
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M3 - Article
C2 - 11299235
AN - SCOPUS:0035026286
VL - 280
SP - H2306-H2312
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 5 49-5
ER -