The mechanism of spironolactone against calcineurin-dependent cardiac hypertrophy in renal hypertension rats
Chang Lian
Abstract
Chang Lian
Abstract
Objective To determine the mechanism of spironolactone against calcineurin dependent cardiac hypertrophy in renal hypertension rats. Methods The model of renal hypertension rats were established by the operation of “one kidney one clip”. Twenty Wistar rats was divided into 3 groups randomly. One operation group(spiro group, n =7) received oral administration of spironolactone for 4 weeks, while another operation group(op group , n =7) and the sham operation group(sham op group, n =6) received tap water. The ratio of left ventricular weight to body weight (LW/BW) and the activity of CaN in the cadiac tissue were measured. Half quantitative PCR was employed to determine the levels of atrial natriuretic factor(ANF) mRNA in cardiac tissue. The expression of calcineurin(CaN) and NFAT (nuclear factor of activated T cell ) in cardiac tissue was observed by immunohistochemical staining. Results The LW/BW and activity of CaN in spiro group decreased significantly compared with those in op group [LW/BW:(0 26±0 05)% vs (0 35±0 06)% , P 0 05;CaN:(0 14±0 04) A 410/mg protein vs (0 44±0 11) A 410/mg protein, P 0 05].ANF mRNA level in spiro group was similar to that in sham op group but much lower than that in op group ( P 0 05). The lower expression of CaN and NFAT in cardic tissure by immunohistochemical staining in spiro group was also observed. Conclusion The preventive mechanism of spirolactone upon cardiac hypertrophy is related to the decrease of CaN expression and its activity in cardiac tissue.
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Objective To determine the mechanism of spironolactone against calcineurin dependent cardiac hypertrophy in renal hypertension rats. Methods The model of renal hypertension rats were established by the operation of “one kidney one clip”. Twenty Wistar rats was divided into 3 groups randomly. One operation group(spiro group, n =7) received oral administration of spironolactone for 4 weeks, while another operation group(op group , n =7) and the sham operation group(sham op group, n =6) received tap water. The ratio of left ventricular weight to body weight (LW/BW) and the activity of CaN in the cadiac tissue were measured. Half quantitative PCR was employed to determine the levels of atrial natriuretic factor(ANF) mRNA in cardiac tissue. The expression of calcineurin(CaN) and NFAT (nuclear factor of activated T cell ) in cardiac tissue was observed by immunohistochemical staining. Results The LW/BW and activity of CaN in spiro group decreased significantly compared with those in op group [LW/BW:(0 26±0 05)% vs (0 35±0 06)% , P 0 05;CaN:(0 14±0 04) A 410/mg protein vs (0 44±0 11) A 410/mg protein, P 0 05].ANF mRNA level in spiro group was similar to that in sham op group but much lower than that in op group ( P 0 05). The lower expression of CaN and NFAT in cardic tissure by immunohistochemical staining in spiro group was also observed. Conclusion The preventive mechanism of spirolactone upon cardiac hypertrophy is related to the decrease of CaN expression and its activity in cardiac tissue.
Key concepts: Calcineurin, Internal medicine, Endocrinology, Spironolactone, NFAT, Medicine, Immunohistochemistry, Muscle hypertrophy