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Effect of Tianma Shuxin Granules on the blood pressure and the mRNA and protein expression of ACE, ACE2 and Mas in the spontaneous hypertensive rats′ third-order branches of mesenteric arteries |
LIU Kun XU Guicheng YIN Yijian PAN Limin WANG Yang |
Department of General Internal, Guang′anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China |
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Abstract Objective To observe the effect of Tianma Shuxin Granules (TSG) to spontaneous hypertensive rats (SHRs) on the blood pressure (BP), as well as the mRNA and protein expression of angiotensin-converting enzyme (ACE), ACE2 and Mas in the third-order branches of mesenteric arteries, and investigate the possible mechanisms of SHRs′ resistance vascular eutrophic remodeling and the intervention of TSG. Methods Eighty male SPF SHRs were divided into five groups with 16 rats in each group according to the random number table method: high dosage traditional Chinese medicine group [11.592 g/(kg·d) TSG], medium dosage traditional Chinese medicine group [5.796 g/(kg·d) TSG] and low dosage traditional Chinese medicine group [2.898 g/(kg·d) TSG], Western medicine control group and model control group were treated with TSG, Losartan Potassium Suspension and distilled water respectively. Fifteen Wistar rats were taken as normal control group. The BP of rat tail artery was measured fortnightly. After 18 weeks, rats in each group were killed and the mesenteric arteries were separated. The protein and mRNA expression of ACE, ACE2 and Mas were measured by Western blot and RT-PCR respectively. Results After 2 weeks of administration, the BP of the Western medicine control group, the high dosage traditional Chinese medicine group and the middle dosage traditional Chinese medicine group were significantly lower than that of the model control group (P < 0.01). Compared with the normal control group, the mRNA and protein expression of ACE in the model control group were increased significantly (P < 0.05 or P < 0.01), and the content and the protein expression of mRNA of ACE2 and Mas were decreased significantly (P < 0.05 or P < 0.01). Compared with the model control group, the mRNA expression of ACE in the high dosage traditional Chinese medicine group was decreased (P < 0.05), the mRNA expression of Mas was increased (P < 0.05), the protein expression of ACE2 and Mas were increased (P < 0.01). The mRNA and protein expression of ACE were decreased (P < 0.05), the mRNA expression of ACE2 and the protein expression of Mas were increased in the medium dosage traditional Chinese medicine group (P < 0.05 or P < 0.01). The mRNA expression of ACE was decreased (P < 0.05), the mRNA and protein expression of Mas were increased in the low dosage traditional Chinese medicine group (P < 0.05 or P < 0.01). Conclusion TSG has markedly effect in lowering SHRs′ BP. Increased synthesis of ACE, and decreased synthesis of ACE2 and Mas may be one of the pathological mechanisms of vascular nutrition-rich remodeling in hypertension resistance. TSG can reverse the imbalance of ACE and ACE2, increase the expression of Mas, it can reverse the imbalance of RAS by means of interfering the ACE2 - Ang (1-7) - Mas pathways, it is beneficial to improve the vascular hypertension resistance eutrophic remodeling and reduce the target-organ damage.
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