Effects Of Anti-Hypertensive Drugs On Expression Of TRPC3 And TRPC6 In The Left Ventricle Of Spontaneously Hypertensive Rats

Background Left ventricle hypertrophy (LVH) is one of the most common complications of hypertension, and can finnally cause heart failure. And the disturbance of calcium circulation while left ventricle hypertrophy plays an important role in the development of heart failure. So in the treatment of hypertension, preventting and reversing left ventricle hypertrophy while controlling the blood pressure are always hotspot and nodus of researches about hypertension.Clinically, some hypertension patients'LVH are still hard to reverse in spite of well-controlled blood pressure; some patients'elevated blood pressure level are not parallel with their LVH level. Pharmacology test showed :some anti-hypertensive drugs can control blood pressure ,but cann't prevent and reverse LVH,while other drugs can inhibit LVH to take place ,but cann't improve blood pressure .There is still no conculsion about the mechanism of LVH caused by different reasons. So, it's urgent to probe the mechanism of the development of LVH, and to find new drug target point, intervene early to prevent and reverse the development of LVH.Changes of intracellular calcium concentration of cadiomyocyte is the initial agent to trigger the signal transduction related to myocardial hypertrophy, however, calcium channels mediated those changes of intracellular calcium concentration is not clear. Recent rearches show canonical transient potential receptor channels (TRPC) have relations with the progress of LVH and play an important role.However, researches on effects of TRPC in cardiovascular system just start, and have no conculsions.Our research taking spontaneously hypertensive rats(SHR) as animal modle, to investigate the effects of TRPC3 and TRPC6 in the development of LVH,and effects of anti-hypertensive drugs on these two TRPC subfamily.Objective(1) To investigate the mRNA and protein expression of TRPC3 and TRPC6 in the left ventricle of SHR and Wistar Kyoto rats (WKY).(2) To investigate the relation between the level of LVH and blood pressure level in SHR and WKY after antihypertensive drugs intervening.(3) To observe changes of the mRNA and protein expression of TRPC3 and TRPC6 in the left ventricle of SHR and WKY after antihypertensive drugs intervening.(4) To investigate the possible mechanism of TRPC3 and TRPC6 in the development of left ventricle hypertrophy caused by overloaded pressure.Methods Twenty-four twelve-week SHRs were randomly divided into 4 groups: SHR group, valsartan group, ramipril group and amlodipine group, six in each group.and another Wistar Kyoto rats (WKY) were used as control group.After 4 weeks of drug intervention , Blood pressure (BP), left ventricular mass index (LVMI) and left ventricular cardiomyocytes transection diameter (LVTDM) were examined ,and RT-PCR and Western Blot were used to deteced the expressions of TRPC3 /6 mRNA and protein.Results Compared with those in WKY, BP, LVMI and LVTDM in SHR were significantly higher(P<0.05)and the data mentioned above decreased significantly in drug intervention groups(P<0.05). Expressions of TRPC3 and TRPC6 mRNA and protein were detected in each group, and were significantly higher compared with those in WKY. TRPC3 decreased dramatically in drug intervention groups (P<0.05) and TRPC3 mRNA and protein decreased significantly in Val group compared with those in Ram group and Aml group. However, no significant changes in TRPC6 mRNA and protein expressions were observed in drug intervention groups.Conclusion⑴Expressions of TRPC3 and TRPC6 are found in SHR and WKY.⑵TRPC3 and TRPC6 may co-regulate the pathphysiological processes of myocardial hypertrophy. ⑶Valsartan and Ramipril may inhibit left ventricle hypertrophy probably by down-regulating mRNA and protein expression of TRPC3.