Hypertension in response to CD4(+) T cells from reduced uterine perfusion pregnant rats is associated with activation of the endothelin-1 system.
Hypertension in response to CD4(+) T cells from reduced uterine perfusion pregnant rats is associated with activation of the endothelin-1 system.
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DOI：
10.1152/ajpregu.00049.2012
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发表时间：
2012-07
期刊：
影响因子：
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通讯作者：
K. Wallace;Sarah Novotny;J. Heath;Janae Moseley;J. Martin;M. Owens;B. LaMarca
中科院分区：
文献类型：
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作者：
K. Wallace;Sarah Novotny;J. Heath;Janae Moseley;J. Martin;M. Owens;B. LaMarca
我们已经证明，从胎盘缺血（子宫胎盘灌注减少，RUPP）大鼠中过继转移CD 4（+）T细胞会导致妊娠期间高血压和炎症细胞因子升高。在这项研究中，我们验证了RUPP CD 4（+）T细胞过继转移与内皮素-1活化相关的假设，内皮素-1活化是妊娠期间血压升高的一种机制。在妊娠第13天将来自RUPP或正常妊娠（NP）大鼠的CD 4（+）T细胞过继转移到NP大鼠中。在妊娠第19天分析平均动脉压（MAP），并收集组织进行内皮素-1分析。胎盘缺血性RUPP大鼠的MAP比NP大鼠升高（124.1 ± 3 vs. 96.2 ± 3 mmHg; P = 0.0001），RUPP CD 4（+）T细胞的NP受体的MAP升高（117.8 ± 2 mmHg; P = 0.001，与NP相比）。RUPP CD 4（+）T细胞的连续转移使胎盘前内皮素原-1mRNA增加，与NP CD 4（+）T细胞大鼠相比增加2.1倍，与NP相比增加1.7倍。内皮细胞分泌内皮素-1的能力为52.2 ± 1.9pg·mg（-1）·ml（-1），RUPP组为77.5 ± 4.3pg·mg（-1）·ml（-1（P = 0.0003）; NP+NP CD 4（+）T细胞血清为47.2 ± .16 pg·mg（-1）·ml（-1），NP+RUPP CD 4（+）T细胞血清为62.2 ± 2.1 pg·mg（-1）·ml（-1）（P = 0.002）。为了检测内皮素-1在RUPP CD 4（+）T细胞诱导的高血压中的作用，通过饮用水给予妊娠大鼠内皮素A（ET（A））受体拮抗剂（ABT-627，5 mg/kg）。NP+ET（A）阻断组MAP为92 ± 2 mmHg，RUPP+ET（A）阻断组MAP为108 ± 3 mmHg，NP+NP CD 4（+）T细胞+ET（A）阻断组MAP为95 ± 5 mmHg，NP+RUPP CD 4（+）T细胞+ET（A）阻断组MAP为102 ± 2 mmHg。这些数据表明，内皮素-1激活的重要性，导致高血压通过长期暴露于活化的CD 4（+）T细胞，对胎盘缺血的反应。
We have shown that adoptive transfer of CD4(+) T cells from placental ischemia (reduction in uteroplacental perfusion, RUPP) rats causes hypertension and elevated inflammatory cytokines during pregnancy. In this study we tested the hypothesis that adoptive transfer of RUPP CD4(+) T cells was associated with endothelin-1 activation as a mechanism to increase blood pressure during pregnancy. CD4(+) T cells from RUPP or normal pregnant (NP) rats were adoptively transferred into NP rats on gestational day 13. Mean arterial pressure (MAP) was analyzed on gestational day 19, and tissues were collected for endothelin-1 analysis. MAP increased in placental ischemic RUPP rats versus NP rats (124.1 ± 3 vs. 96.2 ± 3 mmHg; P = 0.0001) and increased in NP recipients of RUPP CD4(+) T cells (117.8 ± 2 mmHg; P = 0.001 compared with NP). Adoptive transfer of RUPP CD4(+) T cells increased placental preproendothelin-1 mRNA 2.1-fold compared with NP CD4(+) T cell rats and 1.7-fold compared with NP. Endothelin-1 secretion from endothelial cells exposed to NP rat serum was 52.2 ± 1.9 pg·mg(-1)·ml(-1), 77.5 ± 4.3 pg·mg(-1)·ml(-1) with RUPP rat serum (P = 0.0003); 47.2 ± .16 pg·mg(-1)·ml(-1) with NP+NP CD4(+) T cell serum, and 62.2 ± 2.1 pg·mg(-1)·ml(-1) with NP+RUPP CD4(+) T cell serum (P = 0.002). To test the role of endothelin-1 in RUPP CD4(+) T cell-induced hypertension, pregnant rats were treated with an endothelin A (ET(A)) receptor antagonist (ABT-627, 5 mg/kg) via drinking water. MAP was 92 ± 2 mmHg in NP+ET(A) blockade and 108 ± 3 mmHg in RUPP+ET(A) blockade; 95 ± 5 mmHg in NP+NP CD4(+) T cells+ET(A) blockade and 102 ± 2 mmHg in NP+RUPP CD4(+) T cells+ET(A) blockade. These data indicate the importance of endothelin-1 activation to cause hypertension via chronic exposure to activated CD4(+) T cells in response to placental ischemia.