Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension
Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension
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DOI：
10.1172/jci3685
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发表时间：
1998-08-01
影响因子：
15.9
通讯作者：
Jose, PA
中科院分区：
文献类型：
--
作者：
Asico, LD;Ladines, C;Jose, PA
由于多巴胺受体在肾脏和心血管功能的调节中是重要的，我们研究了D-3受体（D-2样受体家族的一员，在肾脏近端小管和肾小球细胞中表达）的破坏对心血管的影响。杂合子和纯合子小鼠的收缩压和舒张压高于野生型小鼠（接近20 mmHg）。急性盐水负荷增加尿流率和钠排泄量在野生型和杂合子小鼠中的程度相似，但在纯合子小鼠中的增加减弱。纯合子小鼠的肾脏肾素活性远高于野生型小鼠;杂合子小鼠的肾脏肾素活性介于两者之间。阻断血管紧张素II亚型1受体可使突变小鼠的收缩压下降持续时间长于野生型小鼠。因此，D3受体的破坏增加了肾肾素的产生，并产生肾钠潴留和肾素依赖性高血压。
Since dopamine receptors are important in the regulation of renal and cardiovascular function, we studied the cardiovascular consequences of the disruption of the D-3 receptor, a member of the family of D-2-like receptors, expressed in renal proximal tubules and juxtaglomerular cells. Systolic and diastolic blood pressures were higher (similar to 20 mmHg) in heterozygous and homozygous than in wild-type mice. An acute saline load increased urine flow rate and sodium excretion to a similar extent in wild-type and heterozygous mice but the increase was attenuated in homozygous mice. Renal renin activity was much greater in homozygous than in wild-type mice; values for heterozygous mice were intermediate, Blockade of angiotensin II subtype-1 receptors decreased systolic blood pressure for a longer duration in mutant than in wild-type mice. Thus, disruption of the D3 receptor increases renal renin production and produces renal sodium retention and renin-dependent hypertension.