Study Of Rhynchophylline Infulence On Vascular Endothelial Function In Spontaneously Hypertensive Rats

Objective: 1. To observe the effect of blood pressure of rhynchophylline(Rhy) on spontaneously hypertensive rats(SHR) in different time after sigle administration,and decide the affective doses on anti-hypertensive of Rhy.2. To research the effect of Rhy on plasma levels of asymmetric two dimethylarginine(ADMA), angiotensin II(Ang II), angiotensin type 1 receptor(AT1R), endothelin-1(ET-1), and serum levels of hepatocyte growth factor(HGF), nitric oxide(NO), nitric oxide synthetase(NOS) after successive administration, and investigate the antihypertensive effect and protect effect on vascular endothelial and the mechanism after long-time administration Rhy.Methods 1.Sigle administration: 70 Mal SHRs were randomly divided into the model group, Rhy groups(including 1.25, 2.50, 5.00, 10.00, 20 mg/kg), captopril group(6.25mg/kg). Another 10 SD rats were included as the control group. Rats in model and control groups were given the same volume of distilled water. Rat tail artery SBP was measured before administration and after it 0.5,1,2,3 h by a tail measurement device, for 3 times and get the mean.2. Successive administration: 50 Mal SHRs were randomly divided into the model group, the high(H)-, mid(M)-, and low(L)- dose(5.00, 2.50, 1.25mg/kg) Rhy groups, captopril group(6.25mg/kg). Another 10 SD rats were included as the control group. Rats in model and control groups were given the same volume of distilled water once daily for 21 days. Rat tail artery SBP was measured before administration and 7th, 14 th, and 21 th during the administration. The plasma levels of ADMA, Ang II, AT1 R, ET-1 and the serum levels of HGF, NO, NOS after the last administration were measured by Enzyme-Linked Immuno Sorbent Assay(ELISA). Aortic morphological change was observed with HE staining. The apoptosis of cells in abdominal aortas were measuredby terminal dexynucleotidyl transferase(TDT)-mediated d UTP nick labeling(TUNEL)staining. The expression of HGF, c-Met and PPARγ in abdominal aortas were measured by Western blotting.Results 1. Sigle administration: Rhy significantly decreased SBP of SHRs after sigle administration, and the effect is similar to captopril.2. Successive administration: Rhy significantly decreased SBP of SHRs after administration 21 days. Compared with the control group, the plasma levels of ADMA, Ang II, AT1 R, ET-1 were up-regulated, and the serum levels of HGF,NO and NOS were decreased in model group, which could be reversed by the treatment of Rhy(P<0.05 or P<0.01). Rhy(H) and Rhy(M) groups increased the expression of HGF, c-Met, PPARγ in abdominal aorta significantly(P<0.05), and protected aortic endothelial injury.Conclusion Rhy can effectively decreased SBP of SHRs and interfere the plasma levels of ADMA, Ang II, AT1 R, ET-1 and the serum levels of HGF, NO, NOS the serum HGF, NO, NOS, and increased the expression of HGF, c-Met, PPARγ in abdominal aorta significantly,and protect aortic endothelial injury which might be have a protection on vascular endothelial function.