Angiotensin II stimulates superoxide production via both angiotensin AT 1A and AT 1B receptors in mouse aorta and heart

Abstract

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.