Angiotensin II stimulates superoxide production via both angiotensin AT1A and AT1B receptors in mouse aorta and heart.
The present study was conducted to determine the roles of angiotensin AT(1A) and AT(1B) receptors in angiotensin II-induced superoxide anion production in mouse aorta and heart. Superoxide anion production in aorta was determined by the lucigenin chemiluminescence method, and thiobarbituric acid reactive substances in heart tissues were measured by biochemical assay. The basal production rate of superoxide anion in aorta of wild type (WT) mice was significantly higher than in angiotensin AT(1A) receptor knockout (AT(1A) KO) mice. Angiotensin II (2.8 mg/kg/day, s.c. for 13 days) significantly increased superoxide anion production in aorta of both AT(1A) KO and WT mice. However, the superoxide anion production rate in aorta of angiotensin II-infused AT(1A) KO mice was significantly lower than in angiotensin II-infused WT mice. Valsartan (40 mg/kg/day in drinking water) prevented angiotensin II-induced superoxide anion production in aorta of WT and AT(1A) KO mice. Similarly, thiobarbituric acid reactive substances levels in heart tissues of angiotensin II-treated WT and AT(1A) KO mice were significantly higher than those in vehicle-infused WT and AT(1A) KO mice, respectively. Valsartan prevented angiotensin II-induced increases of thiobarbituric acid reactive substances levels in heart tissue of both WT and AT(1A) KO mice. These results indicate that angiotensin II stimulates superoxide anion production via both angiotensin AT(1A) and AT(1B) receptors, and that angiotensin AT(1A) receptors appear to play a predominant role in angiotensin II-induced superoxide anion production in mouse aorta and heart.
Rahman
Matlubur
M
Department of Pharmacology, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 61-0793, Japan. yakuri@kms.ac.jp
Kimura
Shoji
S
Nishiyama
Akira
A
Hitomi
Hirofumi
H
Zhang
Guoxing
G
Abe
Youichi
Y
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000172:deficiency / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*
D044140:Receptor, Angiotensin, Type 1; D013481:Superoxides; D000804:Angiotensin II