Studies On Arterial AT1R,eNOS And Vascular Remodeling In Salt-sensitive Hypertensive Rat By Sensory Nerve Injury

ObjectiveTo detect the expression of AT1R, eNOS of artery in mRNA and protein levels and the changes of vascular structure. To analyse the relationship among AT1R, eNOS and vascular remodeling, so as to explore the molecular mechanism of vascular remodeling in the salt-sensitive hypertension rats induced by sensory denervation, providing the theory basis for prevention and treatment in the salt sensitive hypertension.MethodIn this hypertension model, newborn male Wistar rats were given50mg/kg capsaicin subcutaneously on the1st and2nd day. Control rats were treated with vehicle. After the weaning period (4weeks), male rats were grouped as the following, giving a high salt diet (4%) or normal salt diet (1%) for4weeks:capsaicin and high sodium diet (CAP+HS); capsaicin and normal salt diet (CAP+NS);vehicle control and high salt diet (CON+HS); vehicle control and normal salt diet (CON+NS).Tail-cuff systolic blood pressure and body weight were measured. Using the immunohistochemistry and RT-PCR to detect the mRNA and protein expression of AT1R and eNOS in the aorta. The V.G staining detects the collagen content in each group.Results1. Different salt diet after4weeks, tail-cuff systolic blood pressure increased with the most profound magnitude in CAP+HS rats compared with the other3groups(P<0.05).2. Compared with CON-NS group, media thickness(MT) of rats artery increased, but luminal internal diameter(LD) decreased, and MT/LD also increased in the CAP-HS group, the differences are significant(P<0.05).3. Compared with CON-NS group, the mRNA and protein expression of AT1R in the CAP-HS group were significantly increased (P<0.05).4. Compared with CON-NS group, the mRNA and protein expression of eNOS in the CAP-HS group were significantly decreased (P<0.05).5. Compared with the CON-NS group, the collagen content in the CAP-HS group increased dramatically (P<0.05).6. The AT1R expression in the aorta of CAP-HS rats negatively correlated with eNOS in the protein (r=-0.899, P<0.01), and gene levels (r=-0.967, P<0.01)7. The collagen content in vascular media thickness was significantly correlated with the AT1R protein levels in the artery (r=0.889, P<0.01) and the eNOS protein levels in the artery (r=-0.791, P<0.05), and with the AT1RmRNA relative content (r=0.860,P<0.05) and the eNOS ralative content (r=-0.876, P<0.05).Conclusion1. In this experimental condition, the increased blood pressure may be related with the increased AT1R expression and the decreased eNOS in the gene and protein levels.2. The vascular remodeling caused by the increased blood pressure may relate to the alteration of expression of the AT1R and eNOS.