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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 mechanism of D3 dopamine receptor knockout mice (D3 - / -) hypertension in order to understand the regulation of D3 dopamine receptors on blood pressure. Methods The second generation of D3 - / - mice were used to study the changes of blood pressure, urinary sodium excretion, protein / mRNA of D3 receptor, plasma renin activity, norepinephrine concentration, angiotensin Ⅱ 1 (AT1) receptor expression was measured; and ex vivo mesenteric artery incubation to study the stimulation of D3 receptor vasomotor function. Results Regardless of systolic or diastolic blood pressure, D3 - / - mice were significantly higher than wild type (D3 + / +) mice. After salt loading, there was no significant change in blood pressure in both groups, however, the urinary sodium excretion in D3 - / - mice was lower than that in D3 + / + mice in the last 1 time period after salt loading. Analysis of renal renin activity and AT1 receptor expression revealed that D3 - / - mice were higher than D3 + / + mice. There was no difference in norepinephrine levels in the kidneys of the two groups. Antihypertensive effects of the AT1 receptor antagonist D3 - / - mice were marked and sustained. Isolated mesenteric artery studies have found that stimulating the D3 receptor can relax arterial vessels. Conclusion The increase of blood pressure in D3 - / - mice is not only related to the decline of renal excretion of urinary sodium, but also to the dysfunction of vasodilatation mediated by D3 receptor.