The Mechanism By Which Cyclosporin A Inhibits Cardiac Hypertrophy in Renal Hypertension Rats

Objective To determine the mechanism by which Cyclosporin A(CsA) inhibits calcineurin(CaN)-dependent cardiac hypertrophy in renal hypertension rats. Methods The model of renal hypertension rats were established by the operation of “one kidney one clip(1K1C)”. Twenty Wistar rats were divided into 3 groups randomly: ①Hypertension group(n=7): 1K1C+0.9% NaCl 1 mL·kg -1·d -1 intraperitoneally and 0.9%NaCl in drinking of water for 4 weeks; ②CsA group(n=7):1K1C+CsA 5 mg·kg -1·d -1 intraperitoneally and 0.9% NaCl in drinking 4 weeks; ③sham operation group(n=6): sham operation +0.9% NaCl 1 mL·kg -1·d -1 intraperitoneally and in drinking for 4 weeks. The ratio of left ventricle weight to body weight(LW/BW) and the activity of CaN in the cardiac tissue were measured. Half quantitative PCR was employed to determine the levels of atrial natriuretic factor(ANF) mRNA and CaN mRNA in cardiac tissue. The expressions of CaN and NFAT (nuclear factor of activated T cell ) in cardiac tissue were examined by immunohistochemical staining. Results The ratio of LW/BW and activity of CaN in CsA group was decreased significantly compared with untreated group (LW/BW:0.27%±0.03% vs 0.35%±0.06%,P0.05;CaN: 0.18±0.05 A410/mg protein vs 0.44±0.11 A410/mg protein, P0.05). CaN and ANF mRNA level in CsA group was similar with that of sham operation group and much lower than that in untreated group(P0.05). In CsA group, the lower expression of CaN and NFATc3 in cardiac tissue was also shown. Conclusion The preventive mechanism of CsA cardiac hypertrophy is related to the decrease of CaN expression and its activity in cardiac tissue.