Effect Of Anti-Hypertensive Medication On Expression Of TRPC3 And TRPC6 In The Aorta Of Spontaneously Hypertensive Rats

Background and Object: Hypertension is a common disorder and has elevated the risk of cardiovascular-associated morbidity and mortality. The pathogenesis of hypertension has not yet been fully elucidated. Now, transient receptor potential canonical (TRPC) channels, non-selective cation channel, which have also been identified as important players in the regulation of hypertension is becoming a hot research. Recent data reveal that transient receptor potential canonical type 3 (TRPC3) channels and transient receptor potential canonical type 6 (TRPC6) channels are closely associated with essential hypertension, however, anti-hypertensive medication on the role of TRPC channels has just begun. We designed this study to observe the effect of Ramipril, Valsartan and Amlodipine on expression of TRPC3 channel and TRPC6 channel in the aorta of spontaneously hypertensive rats(SHR), to investigate their potential mechanisms in blood pressure regulation, and to provid experimental proof for searching more effective treatment of essential hypertension in clinical work. Methods: A total of 24 healthy male SHR were randomly divided into 4 groups: Ramipril group (1mg/kg·d), Valsartan group (30mg/kg·d), Amlodipine group (5mg/kg·d), and Experimental control group, the rats had normal saline. Additionally, we set up a Blank control group with WKY rats. n=6 in each group. All animals were treated for 4 weeks. 4 weeks after anti-hypertensive medication, blood pressure was measured, the expression of TRPC3 and TRPC6mRNA in aorta was measured by Reverse transcription pclymerase chain reaction (RT-PCR), the expression of TRPC3 and TRPC6 in aorta localization was observed by immunohistochemistry staining, and the expression of TRPC3 and TRPC6 protein in aorta was measured by Immunoblot (Western Blot, WB).Result: (1)Compared with black control group, the systolic blood pressure (SBP) of experimental control group was significantly increased (P<0.05), the expression of mRNA and the protein level of TRPC3 and TRPC6 in aorta was significantly increased (P<0.05). (2)Compared with experimental control group, the SBP of Ramipril group, Valsartan group, Amlodipine group was significantly decreased(P<0.05), meanwhile, the expression of mRNA and the protein level of TRPC3 in aorta was significantly decreased(P<0.05), however, the expression of mRNA and the protein level of TRPC6 in aorta was no significant difference(P>0.05). (3)Among in Ramipril, Valsartan, and Amlodipine group, the SBP and the expression of mRNA and the protein level of TRPC3 and TRPC6 in aorta were no significantly difference(P>0.05).Conclusion: (1)Compared with black control group, the expression of TRPC3 and TRPC6 in aorta was significantly increased, implying that TRPC3 and TRPC6 channels might be involved in the regulation of blood pressure in SHR. (2) Ramipril, Valsarten and Amlodipine could significantly reduce the expression of TRPC3 in aorta , implying that TRPC3 might be the direct or indirect target point of the three anti-hypertensive. (3)Ramipril, Valsarten and Amlodipine could not reduce the expression of TRPC6 in aorta , implying that searching for a specific blocker of TRPC6 might becoming a new drug target in hypertension therapy.