自发性高血压大鼠肾上腺髓质素含量与中性内肽酶分布的关系

Adrenomedullin Contents and the Neutral Endopeptidase Distributions in Blood and Tissues in Spontaneous Hypertensive Rats

目的 测定自发性高血压大鼠 (SHR)与WKY大鼠组织肾上腺髓质素 (ADM )含量和中性内肽酶 (NEP)活性及其表达水平 ,以探讨NEP的变化在高血压时组织ADM水平升高中的意义。方法 采用放射免疫分析方法和荧光分光光度法分别检测血浆和组织的ADM含量和NEP的活性 ,同时用半定量RT PCR和免疫组织化学染色法分别检测组织NEPmRNA和NEP蛋白的表达和分布。结果 ADM和NEP广泛分布于大鼠的血浆和组织 ,SHR的ADM含量在各组织普遍高于WKY大鼠。SHR心脏和小肠NEP的活性和mRNA表达均显著低于WKY大鼠 ,ADM含量与NEP活性呈负相关。反之 ,SHR血浆和肾脏NEP活性、肾脏NEPmRNA水平与蛋白量均高于WKY大鼠 ,ADM含量与NEP活性呈正相关。在肺脏和主动脉 ,NEP的活性无明显变化。结论 NEP在自发性高血压大鼠各组织器官中的变化与ADM含量的变化不一致 ,提示高血压时组织局部的NEP对ADM含量的影响不同。

Objective To study the activity and expression of neutral endopeptidase (NEP) and the adrenomedullin (ADM) contents in various tissues in the spontaneous hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats,and to investigate the possible role of NEPs in the elevating of ADM in blood and tissues within hypertension. Methods ADM contents and NEP activities were measured by radioimmunoassay and fluorospectrophotometry,respectively. The amount of NEP mRNA and NEP protein in different tissues was determined by semi-quantitative RT-PCR and immunohistochemical assay. Results ADM and NEPs were present widely in various tissues. ADM contents were generally higher in SHRs than those of the WKY rats. Compared with the controls,in SHR the NEP activity and mRNA expression in left ventricle and small intestine were lower. ADM contents were inversely correlated with the NEP activity. While the kidney NEP mRNA and protein expression in SHRs were higher than those of the WKY rats,ADM contents was positively correlated with the NEP activity. NEP activity in aorta and lung in SHR was similar to those of the WKY rats. Conclusion In spontaneous hypertensive rats,the NEP activity was various in different tissues,but the ADM contents elevated generally indicating the local concentrations ADM in various tissues might be regulated by the NEPs differently.