摘要
目的肾脏血管紧张素Ⅱ1型受体(AT1R)的保钠潴水功能部分可以解释AT1R基因敲除(AT1A-/-)小鼠血压降低的原因,然而,对于是否有AT1R以外的机制参与则研究较少。既往的研究间接提示D5多巴胺受体和AT1R之间存在相互抑制作用,因而在本实验中,将验证D5受体的因素是否参与AT1A-/-小鼠低血压的发生。方法在比较AT1A-/-小鼠和其对照(AT1A+/+)小鼠血压、尿钠排泄、肾脏D5受体表达的基础上,利用Wistar-Kyoto(WKY)大鼠的肾近曲小管(RPT)细胞株和D5受体转染HEK293细胞为研究对象,研究AT1R和D5受体之间的交互影响,探讨AT1A-/-小鼠血压降低的原因。结果与AT1A+/+小鼠相比,低盐饮食的状况下AT1A-/-小鼠血压较低、尿钠排泄能力增强,肾脏D5受体表达量增加。在WKY大鼠肾近曲小管的细胞上,刺激AT1R可特异地抑制D5受体的表达;反过来,刺激D5受体转染HEK293细胞的D5受体也可抑制AT1R的表达。结论D5受体的高表达可能参与了AT1A-/-小鼠血压降低的发生机制。
Objective The hypotension of AT1 receptor knockout mice （AT1A^-/- ） can be, at least in part, explained by AT1 receptor deficiency. However, whether there is mechanism beyond ATI receptor is not known. Our previous study showed negatively interaction between Ds dopamine receptor and AT1 receptor. Based on a- bove-mentioned evidences, we hypothesize that Ds receptor is involved in the pathogenesis of hypotension of ATIA^-/- mice. Methods Blood pressure, urine natriuretic excretion, renal Ds receptor expression were investi- gated in ATIA^-/- mice and their control （ATlA^＋/＋ ） mice. Furthermore, the mutual interaction between AT. receptor and Ds receptor was also investigated in renal proximal tubule （RPT） cells from Wistar-Kyoto（WKY） rats and Ds receptor transfected HEK293 cells. Results As compared with ATIA＋/＋ mice, AT1A^-/- mice on lowsalt diet had lower blood pressure, higher renal Ds receptor expression. Stimulation of AT1 receptor with angiotensin II decreased Ds receptors in WKY cells. Moreover, stimulation of D5 receptor also decreased AT1 receptor expression in Ds receptor transfected HEK293 cells. Conclusion Higher renal D5 receptor expression might be involved in the pathogenesis of hypotension of AT1A^-/- mice.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2007年第11期917-920,共4页
Chinese Journal of Hypertension
基金
国家自然基金30470728
30672199
美国NIH基金HL074940
