D3多巴胺受体基因敲除小鼠高血压产生机制的探讨

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.

Hypertension in D3 dopamine receptor deficient mice

OBJECTIVE: To investigate the mechanisms by which hypertension occurs in D(3) dopamine receptor null mice (D(3)-/-). METHODS: Several parameters, including blood pressure, renal sodium excretion, D(3) receptor protein and mRNA expression, plasma renin activity, norepinephrine concentration and AT(1) receptor expression were checked in D(3)-/- mice and their littermate wild type mice (D(3)+/+). Moreover, the vasorelaxant effect of D(3) receptor stimulation was measured with ex-vivo mesenteric artery isolated from Wistar-Kyoto rats. RESULTS: Blood pressure was higher in D(3)-/- mice compared with that in D(3)+/+ mice, salt-loading had no effect on blood pressure in both groups, at the last period, sodium excretion was lower in D(3)-/- mice as compared with D(3)+/+ mice, renal renin activity and AT(1) receptor expression were higher in D(3) -/- [corrected] mice than in D(3) +/+ [corrected] mice. In contrast, no difference of renal norepinephrine was found in two groups. When using angiotensin II 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 D(3) receptor was stimulated. CONCLUSIONS: Elevation of blood pressure in D(3)-/- mice might be related with impaired renal sodium excretion and vaso-relaxation in resistance artery.