Important role of local angiotensin II activity mediated via type 1 receptor in the pathogenesis of cardiovascular inflammatory changes induced by chronic blockade of nitric oxide synthesis in rats.
BACKGROUND
The chronic inhibition of NO synthesis by N(omega)-nitro-L-arginine methyl ester (L-NAME) upregulates the cardiovascular tissue angiotensin II (Ang II)-generating system and induces cardiovascular inflammatory changes in rats.


RESULTS
We used a rat model to investigate the role of local Ang II activity in the pathogenesis of such inflammatory changes. Marked increases in monocyte infiltration into coronary vessels and myocardial interstitial areas, monocyte chemoattractant protein-1 (MCP-1) expression, and nuclear factor-kappaB (NF-kappaB, an important redox-sensitive transcriptional factor that induces MCP-1) activity were observed on day 3 of L-NAME administration. Along with these changes, vascular superoxide anion production was also increased. Treatment with an Ang II type 1 receptor antagonist or with a thiol-containing antioxidant, N-acetylcysteine, prevented all of these changes.


CONCLUSIONS
Increased Ang II activity mediated via the type 1 receptor may thus be important in the pathogenesis of early cardiovascular inflammatory changes in this model. Endothelium-derived NO may decrease MCP-1 production and oxidative stress-sensitive signals by suppressing localized activity of Ang II.
Usui
M
M
Research Institute of Angiocardiology, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Egashira
K
K
Tomita
H
H
Koyanagi
M
M
Katoh
M
M
Shimokawa
H
H
Takeya
M
M
Yoshimura
T
T
Matsushima
K
K
Takeshita
A
A
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics; D003331:Coronary Vessels / Q000473:pathology*; D007249:Inflammation / Q000209:etiology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity*; D009569:Nitric Oxide / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism
D018932:Chemokine CCL2; D016328:NF-kappa B; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A; D019331:NG-Nitroarginine Methyl Ester