Effect of active immunization against angiotensin II type 1 (AT1) receptor on hypertension & arterial remodelling in spontaneously hypertensive rats (SHR).
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Date
2014-04
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Abstract
Background & objectives: angiotensin II receptor type 1 (AaT1) is known to be involved in the pathogenesis of hypertension. tThis study was undertaken to explore the effect of active immunization against AaT1 receptor on blood pressure and small artery remodelling in spontaneously hypertensive rat (SHR).
Methods: Male SHR and Wistar rats aged two months were actively immunized with different peptides (AaTR12185、AaTR10014 and AaTR12181) corresponding to particular sequences of rat receptor, while another SHR group was given losartan (10 mg/kg/day) orally once a day. Aanti-AaT1 receptor antibodies were detected by ELISAa and blood pressure was measured. The effect of the antibodies on the artery and vascular smooth muscle cells (VSMCs) proliferation was studied.
Results: all immunized animals produced antibodies against the particular peptides. The systolic blood pressure was decreased in the SHR immunized with peptide-AaTR12181 compared with the control. However, no changes were observed in the SHR immunized with other two peptides. The Wistar rats immunized with the three peptides did not show any changes in blood pressure. The media/lumen area ratio of the mesenteric artery was reduced in SHR immunized with and similar to that of the SHR treated with losartan. The antibody from SHR immunized with AaTR12181 had no effect on the proliferation of VSMC. But it could inhibit the proliferation caused by angiotensin II and its effect at the titre of 1:40 was similar to that of 1μmol/l losartan.
Interpretation & conclusions: Our findings demonstrated that the antibody from SHR immunized with AaTR12181 had the effect of reducing blood pressure and target organ protection similar to losartan. Aactive immunization against AaT1 receptor may be a promising strategy in future for the treatment of hypertension.
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Keywords
Antibody, AT1 receptor, proliferation, SHR, vascular smooth muscle cell
Citation
Li Liu-Dong, Tian Miao, Liao Yu-Hua, Zhou Zi-Hua, Wei Fen, Zhu Feng, Wang Min, Wang Bin, Wei Yu-Miao. Effect of active immunization against angiotensin II type 1 (AT1) receptor on hypertension & arterial remodelling in spontaneously hypertensive rats (SHR). Indian Journal of Medical Research. 2014 Apr;139 (4): 619-624.