Salt-induced Vascular Remodeling and Telmisartan Intervention in Wistar Rats
|School||Zunyi Medical College,|
|Course||Cardiovascular within science|
|Keywords||high Salt vascular remodeling TGF-β1/smads RAAS|
Objective:To investigate the effects of high dietary salt intake on blood pressure and vascular remodeling and the prevention of Telmisartan.Methods:60 Wistar rats were randomly divided into normal control group, high salt (8%) model group and high salt+telmisartan group. Tail-cuff artery pressure was determined every 2 weeks. After 24 weeks, high salt model group was divided into model hypertension (MH) group and model normal pressue (MN) group. At end of the experiment, aorta and mesenteric artery were collected after pressure measurement of carotid artery。Media thickness (MT), lumen diameter (LD) and ratio of media to lumen (MT/LD) of aorta and mesenteric artery were measured through HE staining. The collagen volume fraction was detected by Masson staining. The content of AngⅡand ALD were assessed by radio-immunoassay, and the activity of Na--K--ATPase and Ca2+-ATPase of the vascular media was measured by spectrophotography. Real-time PCR was employed to detect the mRNA expression of Na+-K+-ATPase al subunit, plasma membrane Ca2+-ATPase isoforml(PMCA1), AT1R and AT2R.The protein expression of TGF-β1、Smad2/3、Smad7、α-SMA and AT1R in the aorta and mesenteric artery were determined by immunohistochemistry.Results:(1) At 7 week of experiments, tail-cuff blood pressure in MH group was much higher than that in other three groups (P<0.05), and continued to experiment end. At 24 week, carotid artery pressure in MH group was also much higher than in other three groups (P<0.05).Tail-cuff blood pressure and carotid arteries pressure were not statistically significant in the other three groups.(2) Compared with C group and T group, MT, MT/LD ratio and the collagen volume fraction of aorta and mesenteric artery in MH group and MN group increased (P<0.05), the above-mentioned indexes were improved in T group(P< 0.05).(3) The levels of AngⅡamong all groups had no statistically significance, MH group than the C group, aldosterone levels increased trend (P=0.05), Compared with MH, T group aldosterone levels were decreased. Compared with the C group, MH group aortic smooth muscle tissue AT1R gene and protein expression were increased (P<0.05), AT2R gene expression decreased (P<0.05), compared with the MH, T group AT1R gene and protein expression decreased (P<0.05), while no effect on AT2R gene expression.(4) Co-mpared with C group, the mRNA expression of Na+-K-ATPase al subunit in MH and MN groups was decreased than (P<0.05), whereas PMCA1 increased. Furthermore, in MH and MN groups the activity of Na+-K+-ATPase and Ca2+-ATPase was decreased(P< 0.05)than C group.(5) Compared with C group,MH group、MN group aortic and mesente-ic artery TGF-β1、Smad2/3 expression was significantly highter(P<0.01),Smad7 expressi-on was significantly decreased((P<0.01),compared with the MH group, T group of TGF-β1、Smad2/3 was decreased (P<0.05), Smad7 expression was increased (P<0.05).Conclusion:1.Long-term high-salt diet could lead to the remodeling of aorta and mesenteric artery directly or indirectly(elevated blood pressure), the features of vascular remodeling were media thickening, the proliferation of vascular smooth muscle cells and collagen deposition.2.The molecular mechanisms of arterial remodeling induced by high salt may be related to positive and negative components in TGF-β1/Smads signal transduction and upregulating or downregulating AT1R/AT2R in local RAAS. Increased aldosterone and AT1R, the upregulation of TGF -β1 and Smad2/3 may be the main mechanisms in salt-induced hypertension and vascular remodeling.3. The decreased ion pump activity and abnormal gene expression may participate partially in salt-induced hypertension and vascular remodeling.4.Telmisartan may inhibit the proliferation of vascular smooth muscle and collagen accumulation, and prevent high salt-induced hyperte-nsion and vascular remodeling.Its pharmacological mechanisms may be mediated mainly through the inhibition of AT1R expression, decreased of TGF-β1, Smad2/3 signaling pathway and upregulation of Smad7.