摘要
目的探讨D3多巴胺受体基因敲除小鼠(D3-/-)高血压产生的机制,以期了解D3多巴胺受体对血压的调节作用。方法以第2代D3-/-小鼠为研究对象,分别对其血压、肾脏尿钠排泄功能、D3受体的蛋白/mRNA、血浆肾素活性、去甲肾上腺素的浓度、血管紧张素Ⅱ1型(AT1)受体的表达进行测定;并通过离体肠系膜动脉孵育,研究刺激D3受体对血管舒缩功能的影响。结果无论收缩压或舒张压,D3-/-小鼠均明显高于野生型(D3+/+)小鼠。给予盐负荷后,2组小鼠血压均无明显变化,然而在盐负荷后最后1个时间段的尿钠排泄量,D3-/-小鼠低于D3+/+小鼠。分析肾脏肾素活性和AT1受体的表达发现D3-/-小鼠高于D3+/+小鼠。2组小鼠肾脏中去甲肾上腺素的水平无区别。AT1受体拮抗剂的降血压作用D3-/-小鼠明显且持久。离体肠系膜动脉研究发现刺激D3受体可舒张动脉血管。结论D3-/-小鼠的血压升高除与肾脏的尿钠排泄功能下降有关,还与D3受体介导的舒血管功能障碍有关。
Objective To investigate the mechanisms by which hypertension occurs in D3 dopamine receptor null mice （D3 -/- ）. Methods Several parameters, including blood pressure, renal sodium excretion, D3 receptor protein and mRNA expression, plasma renin activity, norepinephrine concentration and AT1 receptor expression were checked in D3 - / - mice and their littermate wild type mice （ D3 ＋ / ＋ ）. Moreover, the vasorelaxant effect of D3 receptor stimulation was measured with ex-vivo mesenteric artery isolated from Wistar-Kyoto rats. Results Blood pressure was higher in D3 -/- mice compared with that in D3 ＋/＋ mice, salt-loading had no effect on blood pressure in both groups, at the last period, sodium excretion was lower in D3 -/- mice as compared with D3 ＋/＋ mice, renal renin activity and AT1 receptor expression were higher in D3 ＋/＋ mice than in D3 -/- mice. In contrast, no difference of renal norepinephrine was found in two groups. When using angiotensin I1 subtype-1 receptor antagonist, the systolic blood pressure declined for a longer duration in mutant mice than in wild-type mice. Vaso-relaxation was found in ex-vivo isolated mesenteric artery when D3 receptor was stimulated. Conclusions Elevation of blood pressure in D3 -/- mice might be related with impaired renal sodium excretion and vaso-relaxation in resistance artery.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2005年第12期1132-1136,共5页
Chinese Journal of Cardiology
