Résumé
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.
Résumé
<p><b>OBJECTIVE</b>To investigate the transcriptional regulation of pacemaker channel I(f) mediated by vasoactive peptide endothelin-1 (ET-1) in neonatal rat ventricular myocytes and its mechanism.</p><p><b>METHODS</b>Neonatal rat ventricular myocytes were enzymatically isolated. I(f) current was recorded using the whole-cell patch-clamp technique. The expression of hyperpolarization-activated cyclic nucleotide-gated channel (HCN) isoforms HCN2 and HCN4 were measured by quantitative RT-PCR.</p><p><b>RESULTS</b>ET-1 increased the expression of HCN2 and HCN4 mRNA in a dose- and time-dependent manner. These effects were blocked by specific ETA receptor antagonist BQ-123 but not the ETB receptor antagonist BQ-788. The effects of ET-1 on HCN2 and HCN4 mRNA expression were not affected by the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB-203580).</p><p><b>CONCLUSION</b>These findings indicate that ET-1 stimulates the expression of pacemaker channel I(f) in cardiomyocytes via ETA receptor through a p38 MAPK-independent signaling pathway, which might be linked to the intrinsic arrhythmogenic potential of ET-1.</p>