Discussion on the effects of tetrandrine on myocardial hypertrophy in renovascular hypertensive rats and its underlying mechanism

Abstract

Objective To investigate the effects of tetrandrine on myocardial hypertrophy in renohypertensive rats and its possible mechanism.Methods The myocardial hypertrophy models were established in two-kidney-one-clip (2K1C)renovascular hypertensive rats.Before renal artery constriction,all the rats were randomly divided into four groups(n=15 per group):(1) the sham-operated control group; (2) the 2K1C renohypertensive group; (3) the tetrandrine group,the two-kidney-one-clip renohypertensive rats were treated with tetrandrine at a dose of 50 ml/kg · d-1 from the post-operated 5th week; (4) the enapril group,the two-kidney-one-clip renohypertensive rats were treated with enapril at a dose of 6 ml/kg· d-1 from the post-operated 5th week.The standard tail-cuff method was used to measure blood pressure in conscious rats.After drug treatment for 8 weeks,the rats were killed and left ventricle was obtained to measure the ratio of left ventricle weight to body weight (LVW/BW),myocardial angiotensin Ⅱ content,and mRNA expressions of inflammatory cytokines tumor necrosis factor-α(TNF-α)and interleukin-1 β (IL-1β).Results Compared with shamgroup[(14.90±3.31)kPa; (1.89±0.27)mg/g; (27.38±7.10)pg/mg; (0.72±0.10)and(0.65±0.10)fold of GAPDH expression],the untreated 2K1C renohypertensive rats exhibited a significant increase in blood pressure [(23.53 ± 3.40) kPa],LVW/BW [(2.83 ± 0.40) mg/g],angiotensin Ⅱ content [(43.51 ± 7.37) pg/mg],and mRNA expressions of TNF-α and IL-1β [(1.47 ± 0.14) and (1.07 ± 0.11) fold of GAPDH expression].Treatment with tetradrine significantly attenuated the increase in blood pressure [(15.81 ± 3.12) kPa] and LVW/BW [(1.94 ±0.31) mg/g],angiotensin Ⅱ content [(31.31 ± 6.69) pg/mg],and mRNA expressions of TNF-α and IL-1β [(0.76 ±0.11) and (0.63 ± 0.09) fold of GAPDH expression].Conclusion Long-term related to its inhibition of local production or release of angiotensin Ⅱ and inflammatory cytokines TNF-α and IL-1β in the myocardium of renohypertensive rats. Key words: Hypertension; Myocardial Hypertrophy; Tetrandrine; AngiotensinⅡ; TNF-α; IL-1β