Objective We investigated the long-term effect of capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, on vascular reactivity in C57BL/6J mice. Design and methods Two-month-old male C57BL/6J mice were fed with regular diet (control group, n=12) and capsaicin-containing diet (capsaicin group, n=12). Tail-cuff systolic blood pressure (SBP) was examined at the baseline and at the end of the intervention. After 6-month treatment with capsaicin, invasive carotid artery blood pressure and heart rate were measured, and the aortic contraction was examined using isometric myograph (Danish Myotech Technology, Denmark). Plasma levels of renin, angiotensinII (AngII) and aldosterone were determined. Vascular smooth muscle cells (VSMCs) were obtained from thoracic aorta of mice and cultured by tissue explant method. AngiotensinII type 1 receptor (AT1R) protein expression was detected by western blotting. Cytosolic calcium level was detected in VSMCs using the fluorescent dye technique. Results SBP, invasive carotid artery blood pressure and heart rate had no difference between two groups. Norepinephrine-induced contraction response in thoracic aorta was not different; while AngII-induced contraction of aortic ring was lower in the capsaicin group than control group (P<0.05). Plasma levels of renin, AngII and aldosterone were not different between the two groups. Treatment with capsaicin significantly decreased AT1R protein expression and AngII-induced calcium entry in cultured VSMCs (P<0.05). Conclusion Long term activation of TRPV1 with dietary capsaicin significantly blunted AngII-induced contraction response in aortic segments, which was related to the down-regulation of AT1R expression and reduction of AngII-induced calcium entry in VSMCs. Objective We investigated the long-term effect of capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, on vascular reactivity in C57BL/6J mice. Design and methods Two-month-old male C57BL/6J mice were fed with regular diet (control group, n=12) and capsaicin-containing diet (capsaicin group, n=12). Tail-cuff systolic blood pressure (SBP) was examined at the baseline and at the end of the intervention. After 6-month treatment with capsaicin, invasive carotid artery blood pressure and heart rate were measured, and the aortic contraction was examined using isometric myograph (Danish Myotech Technology, Denmark). Plasma levels of renin, angiotensinII (AngII) and aldosterone were determined. Vascular smooth muscle cells (VSMCs) were obtained from thoracic aorta of mice and cultured by tissue explant method. AngiotensinII type 1 receptor (AT1R) protein expression was detected by western blotting. Cytosolic calcium level was detected in VSMCs using the fluorescent dye technique. Results SBP, invasive carotid artery blood pressure and heart rate had no difference between two groups. Norepinephrine-induced contraction response in thoracic aorta was not different; while AngII-induced contraction of aortic ring was lower in the capsaicin group than control group (P<0.05). Plasma levels of renin, AngII and aldosterone were not different between the two groups. Treatment with capsaicin significantly decreased AT1R protein expression and AngII-induced calcium entry in cultured VSMCs (P<0.05). Conclusion Long term activation of TRPV1 with dietary capsaicin significantly blunted AngII-induced contraction response in aortic segments, which was related to the down-regulation of AT1R expression and reduction of AngII-induced calcium entry in VSMCs.