Effect of valsartan on vasoconstriction induced by the chronic injury of the adventitia in the rat collared carotid artery
10.3760/cma.j.issn.0253-3758.2011.01.016
- VernacularTitle:缬沙坦对大鼠颈动脉血管外膜损伤后收缩功能的影响及其机制探讨
- Author:
Lian-Na XIE
1
;
Ding-Yin ZENG
;
Hai-Shan ZHANG
;
Dan-Meng SUN
;
Xue-Feng PANG
;
Qi-Gang GUAN
Author Information
1. 中国医科大学附属第一医院
- Keywords:
Blood vessels;
Receptors,angiotensin;
Oxidative stress;
Valsartan
- From:
Chinese Journal of Cardiology
2011;39(1):73-78
- CountryChina
- Language:Chinese
-
Abstract:
Objective Vasoconstriction and vascular hypersensitivity to serotonin were previously shown in animal models of adventitia injury. We investigated the contribution of angiotensin Ⅱ(Ang Ⅱ)/Ang Ⅱ receptors and oxidative stress to vascular contractility and reactivity in this model. Methods Wistar Kyoto rats were divided into 3 groups: normal(n =6, no any intervention, only for measuring the serum Ang d-1). After one week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for one week. Blood flow and vascular reactivity to serotonin were determined one week after injury, the blood from left ventricle was taken to measure the serum Ang Ⅱ concentration by ELISA,and carotids were harvested for morphometry and Western blot analysis. Results Adventitia injury induced lumen cross-sectional area reduction(- 44% vs. - 5%), media diameter increase(62% vs. 10%),blood flow reduction[(2. 79 ± 0. 22)vs.(4. 33 ± 0. 84)ml/min]were significantly attenuated by valsartar. The increased vascular reactivity sensitivity to serotonin in vehicle group was also significantly reduced in valsartan group. Serum Ang Ⅱ concentration was significantly increased in vehicle group [(45.21 ± 4. 52)pg/ml vs.(19. 83 ± 0. 5)pg/ml in normal rats, P = 0. 0148]and the expression of Ang Ⅱtype 1(AT1)receptor, Ang Ⅱ type 2(AT2)receptor, as well as p22pbox in collared arteries were significantly upregulated. Valsartan did not affect the AT1 receptor expression but further increased serum Ang Ⅱ concentration[(89. 73 ±20. 44)pg/ml vs.(45.21 ±4. 52)pg/ml, P =0. 001], and AT2 receptor expression, while downregulated p22phox expressions. Conclusions Collar-induced adventitia injury resulted in chronic vsoconstriction and vascular hypersensitivity to serotonin via increased serum Ang Ⅱ level,upregulated Ang Ⅱ receptors expression in the vascular well, and activated local oxidative stress. These changes could be blocked by valsartan suggesting a crucial role of Ang Ⅱ/Ang Ⅱ receptors on vascular contractility and reactivity changes in this model.
