OBJECTIVEVasoconstriction and vascular hypersensitivity to serotonin were previously shown in animal models of adventitia injury. We investigated the contribution of angiotensin II (AngII)/AngII receptors and oxidative stress to vascular contractility and reactivity in this model.

METHODSWistar Kyoto rats were divided into 3 groups: normal (n = 6, no any intervention, only for measuring the serum AngII concentration), vehicle (n = 12, collared), and valsartan (n = 12, collared + valsartan 30 mg×kg(-1)×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 AngII concentration by ELISA, and carotids were harvested for morphometry and Western blot analysis.

RESULTSAdventitia 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 valsartan. The increased vascular reactivity sensitivity to serotonin in vehicle group was also significantly reduced in valsartan group. Serum AngII 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 AngII type 1 (AT(1)) receptor, AngII type 2 (AT(2)) receptor, as well as p22(phox) in collared arteries were significantly upregulated. Valsartan did not affect the AT(1) receptor expression but further increased serum AngII concentration [(89.73 ± 20.44) pg/ml vs. (45.21 ± 4.52) pg/ml, P = 0.001], and AT(2) receptor expression, while downregulated p22(phox) expressions.

CONCLUSIONSCollar-induced adventitia injury resulted in chronic vasoconstriction and vascular hypersensitivity to serotonin via increased serum AngII level, upregulated AngII receptors expression in the vascular well, and activated local oxidative stress. These changes could be blocked by valsartan suggesting a crucial role of AngII/AngII receptors on vascular contractility and reactivity changes in this model.