缬沙坦和螺内酯联合治疗对血浆肾上腺髓质素和醛固酮的影响

The Effect of Combined Valsartan and Spironolactone Treatment on Plasma Adrenomedullin and Aldosterone in Spontaneously Hypertensive Rats

目的研究缬沙坦、螺内酯以及两者联用逆转自发性高血压大鼠（SHRs）心肌肥厚中血浆肾上腺髓质素（ADM）和醛固酮（Ald）的变化。方法12周龄SHRs 32只，随机分成4组，即对照组、缬沙坦组、螺内酯组、两者联用组，每组各8只，另设WKY大鼠（8只，周龄及体重同SHRs）为正常对照组。尾套法测血压，1次／周，4月后处死大鼠，测定左心室质量指数（LVMI）、心肌胶原含量（MCC）及心肌胶原容积分数（CVF）。放免法测血浆ADM和Ald水平。结果与SHR对照组血压（200±20）mmHg比较，螺内酯组（159±20）mmHg，缬沙坦组（140±20）mmHg，联用组（132±20）mmHg；各用药组经12周治疗后LVMI、MCC、CVF均有明显降低（P均〈0．05～0．01）。缬沙坦组血浆Ald水平稍降低[（350．5±34．8）pg／mL，P〉0．05]出现Ald逃逸现象，螺内酯组下降明显[（310．6±30．6）pg／mL，P〈0．05]，联用组能更明显地降低血浆Ald[（260．4±60．1）pg／mL，P〈0．05]。血浆ADM水平在各组均有不同程度的下降，但仍然显著高于WKY组（P〈0．05或P〈0．01）。结论（1）在SHRs中长期应用AT-1受体拮抗剂可引起血浆Ald逃逸；（2）缬沙坦和螺内酯联合应用逆转高血压左心室肥厚。因为其降低血Ald水平，因此优于单用缬沙坦。（3）ADM作为一个抗重塑的自分泌和（或）旁分泌因子，在左室肥厚消退的情况后有所降低，但仍处于一种较高水平。

Objective To investigate the effect of valsartan and （or） spironolactone on left ventricular hypertrophy left ventricular hypertrophy（ LVH） in associated with changes in plasma adrenomedullin（ ADM） and aldosterone in the SHR. Methods Thirty-two SHRs were randomized to receive placebo（n= 8）, or spironolactone 20 mg/kg （n=8）, or valsartan 30 mg/kg（n=8） and combinaed spironolactone（20 mg/kg） and valsartan （20 mg/kg）（n=8） for 4 months. Spironolactone and valsartan were administered by gavage. SBP, LVMI, myocardial collagen content（MCC）, collagen volume fraction（CCF）, plasma adrenomedullin and aldosterone concentration were determined. Age weight matched WKY rats （n= 8） served as control. Results Valsartan or combined treatment significantly decreased SBP（ valsartan ： 140 ± 20, combined ： 132 ± 20 vs SHR placebo ： 200 ± 20 mm Hg, P〈0.05 and P〈0.01, respectively）. LVMI, CVF and MCC were all decreased in 3 treatment groups, As compared with SHR placebo （350.5±34.8 pg/mL）, spironolactone（310.6±30.6 pg/mL, P〈 0.05）, and combined treatment （280.4 ± 60. 1 pg/mL, P〈 0.01 ）, significantly decreased plasma aldosterone while little changes were found in valsartan group （340.6±31. 3 pg/mL, P〉0.05）, indicating the existence of aldosterone escape. Although valsartan, spironolactone and combined treatment all reduced plasma ADM pronouncedly（P〈0.05）, ADM still remained at a relative higher level in relative to that of WKY rats, Conclusion Long-term treatment of ARB（valsartan） may result in aldosterone escape. Combined spironolactone and valsartan was shown to have better reversal effect on left ventricular hypertrophy than valsartan alone. The role of ADM in remodeling of left ventricular hypertrophy needs further investigation.