Lu Yong Ping, Tsuprykov Oleg, Vignon-Zellweger Nicolas, Heiden Susi, Hocher Berthold
Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
Kidney Blood Press Res. 2016;41(6):770-780. doi: 10.1159/000450567. Epub 2016 Nov 11.
BACKGROUND/AIMS: ET-1 has independent effects on blood pressure regulation in vivo, it is involved in tubular water and salt excretion, promotes constriction of smooth muscle cells, modulates sympathetic nerve activity, and activates the liberation of nitric oxide. To determine the net effect of these partially counteracting mechanisms on blood pressure, a systematic meta-analysis was performed.
Based on the principles of Cochrane systematic reviews, we searched in major literature databases - MEDLINE (PubMed), Embase, Google Scholar, and the China Biological Medicine Database (CBM-disc) - for articles relevant to the topic of the blood pressure phenotype of endothelin-1 transgenic (ET-1+/+) mice from January 1, 1988 to March 31, 2016. Review Manager Version 5.0 (Rev-Man 5.0) software was applied for statistical analysis. In total thirteen studies reported blood pressure data.
The meta-analysis of blood pressure data showed that homozygous ET-1 transgenic mice (ET-1+/+ mice) had a significantly lower blood pressure as compared to WT mice (mean difference: -2.57 mmHg, 95% CI: -4.98∼ -0.16, P = 0.04), with minimal heterogeneity (P = 0.86). A subgroup analysis of mice older than 6 months revealed that the blood pressure difference between ET-1+/+ mice and WT mice was even more pronounced (mean difference: -6.19 mmHg, 95% CI: -10.76∼ -1.62, P = 0.008), with minimal heterogeneity (P = 0.91).
This meta-analysis provides robust evidence that global ET-1 overexpression in mice lowers blood pressure in an age-dependent manner. Older ET-1+/+ mice have a somewhat more pronounced reduction of blood pressure.
背景/目的：内皮素-1（ET-1）在体内对血压调节具有独立作用，它参与肾小管水盐排泄，促进平滑肌细胞收缩，调节交感神经活动，并激活一氧化氮的释放。为了确定这些部分相互抵消的机制对血压的净效应，我们进行了一项系统的荟萃分析。
基于Cochrane系统评价的原则，我们在主要文献数据库——MEDLINE（PubMed）、Embase、谷歌学术和中国生物医学数据库（CBM-disc）中检索了1988年1月1日至2016年3月31日期间与内皮素-1转基因（ET-1+/+）小鼠血压表型主题相关的文章。应用Review Manager 5.0（Rev-Man 5.0）软件进行统计分析。共有13项研究报告了血压数据。
血压数据的荟萃分析表明，与野生型（WT）小鼠相比，纯合子ET-1转基因小鼠（ET-1+/+小鼠）的血压显著降低（平均差值：-2.57 mmHg，95%置信区间：-4.98∼-0.16，P = 0.04），异质性最小（P = 0.86）。对6个月以上小鼠的亚组分析显示，ET-1+/+小鼠与WT小鼠之间的血压差异更为明显（平均差值：-6.19 mmHg，95%置信区间：-10.76∼-1.62，P = 0.008），异质性最小（P = 0.91）。
这项荟萃分析提供了有力证据，表明小鼠体内ET-1的整体过表达以年龄依赖的方式降低血压。年龄较大的ET-1+/+小鼠血压降低更为明显。
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