螺内酯对高血压大鼠主动脉重塑及对血浆肾上腺髓质素的影响

Effects of spironolactone on aorta remodeling and plasma adrenomedullin levels in hypertensive rats

目的探讨螺内酯对高血压动脉重塑的作用以及对血浆肾上腺髓质素(adrenomedullin,ADM)的影响。方法腹主动脉缩窄法建立高血压动物模型,44只雄性Wistar大鼠随机分为4组,高血压模型(model)组、培哚普利(perindopril,peri)组、螺内酯(spironolactone,spi)组以及假手术对照(sham)组。术后1周给药组分别给螺内酯(spironolactone;spi;20mg·kg-1·d-1),培哚普利(perindopril;peri;2mg·kg-1·d-1),总给药时间12周。各组应用超声方法分别进行主动脉壁厚和内径检测,离体动脉环试验测定胸主动脉环对硝普钠(sodiumnitroprusside;SNP;10-9to10-6mol/L)的最大舒张反应性,以及主动脉形态学检测,放免法检测血浆ADM水平。结果与sham组相比model组收缩压(SBP)、超声检测胸主动脉壁厚(ADT)明显增加(P<0.01);形态学检测主动脉内中膜厚度、内中膜厚度/内径比值分别提高19.72%、36.84%(P<0.01);spi组同model组相比,上述指标显著下降(P<0.01);spi组和peri组两组之间上述指标差异无显著性。四组超声检测收缩期和舒张期胸主动脉内径差异无显著性(P>0.05)。四组胸主动脉环对硝普钠的血管最大舒张反应差异无显著性(P>0.05)。血浆ADM水平model组同sham组相比明显提高(P<0.01);spi组和peri组较model组明显下降(P<0.01)。结论醛固酮受体拮抗剂螺内酯能防止血压升高,降低胸主动脉壁增厚,预防主动脉重塑,其效果与血管紧张素转换酶抑制剂培哚普利相比较差异无显著性。应用螺内酯和培哚普利后,血浆ADM水平下降,伴随主动脉壁厚的改善,其机制可能为ADM在高血压中作为代偿性激素,可与RAAS相互拮抗,亦或通过ADM直接作用,逆转主动脉重塑。

Objective To investigate the effects of spironolactone on aorta remodeling and the levels of plasma adrenomedullin in hypertensive rats. Methods The models of hypertensive rat were established by using the method of abdominal aortic construction.44 male Wistar rats were randomly divided into 4 groups, model group： hypertensive rats serving as controls, peri group：hypertensive rats subjected to perindopril treatment,2mg·kg^-1·d^-1 ,spi group：hypertensive rats receiving spironolactone treatment, 20mg·kg^-1·d^-1, sham operation group： sham operative rats serving as controis. Ultrasonic diagnostics was used to detect the thickness and the diastolic and systolic diameter of aorta. The maximal dilatory response to cumulative doses of sodium nitroprusside （SNP; 10^-9 to 10^-6mol/L） was evaluated, and then aorta was detected by morphometry. Plasma adrenomedullin was detected by radioimmunoassay respectively. Results As compared with those in sham operation group, SBP and thickness of aorta in model group were significantly increased （ P〈0.01 ） ; the media thiekness of aorta, the ratio of media thickness vs diameter of lumen of aorta increased by 19.72% ,36.84% respectively （ P〈0.01）;all the parameters above in spi group obviously decreased （ P〈0.01）;there was no significant difference between spi group and peri group. There was no significant difference in systolic and diastolic diameter of aorta among all the groups （ P〉0.05） .The maximal vascular relaxation responses to SNP were alike among four groups （ P〉0.05） .As compared with that in sham operation group,plasma ADM in model group was increased significantly （ P〈0.01 ） ; beth spironolactone and perindopril attenuated the increase of plasma ADM （ P〈0.01 ）. Conclusion Spironolactone could attenuate the increase of SBP, decrease the thickness of aorta, prevent aorta remodeling, its effects is the same as that of perindopril. After treatment of spironolactonc and pefindopril, plasma ADM decreases companying the decrease of aortic thickness, dre action mechanism may be that plasma ADM plays a compensatory role in hypertension by inhibiting RAAS or （and） a direct effect to reverse aorta remodeling.