The alpha(1D)-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction.
The alpha(1D)-adrenergic receptor directly regulates arterial blood pressure via vasoconstriction.
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发表时间：
2002
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通讯作者：
A. Tanoue;Y. Nasa;T. Koshimizu;H. Shinoura;S. Oshikawa;T. Kawai;Sachie Sunada;S. Takeo;G. Tsujimoto
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作者：
A. Tanoue;Y. Nasa;T. Koshimizu;H. Shinoura;S. Oshikawa;T. Kawai;Sachie Sunada;S. Takeo;G. Tsujimoto
为了研究 α(1D)-肾上腺素能受体 (α(1D)-AR) 亚型的生理作用，我们通过基因靶向培育了缺乏 α(1D)-AR (α(1D)(-/-)) 的小鼠，并表征了它们的心血管功能。在 α(1D)-/- 小鼠中，RT-PCR 在所检查的任何组织中均未检测到 α(1D)-AR 的任何转录物，并且其他 α(1)-AR 亚型没有明显上调。放射性配体结合研究表明，在 α(1D)-/- 小鼠中，主动脉中的 α(1)-AR 结合能力丧失，而心脏中的结合能力没有改变。与野生型小鼠相比，未麻醉的 α(1D)-/- 小鼠维持显着较低的基础收缩压和平均动脉压状况，并且根据超声心动图评估，它们的心率或心功能没有显着变化。除低血压外，α(1D)-/- 小鼠对去氧肾上腺素和去甲肾上腺素的升压反应降低了 30-40%。此外，在α(1D)-/-小鼠中，主动脉的收缩反应和分离的灌注肠系膜动脉床对α(1)-AR刺激的升压反应显着降低。我们得出结论，α(1D)-AR 通过血管收缩直接参与全身血压的交感调节。
To investigate the physiological role of the alpha(1D)-adrenergic receptor (alpha(1D)-AR) subtype, we created mice lacking the alpha(1D)-AR (alpha(1D)(-/-)) by gene targeting and characterized their cardiovascular function. In alpha(1D)-/- mice, the RT-PCR did not detect any transcript of the alpha(1D)-AR in any tissue examined, and there was no apparent upregulation of other alpha(1)-AR subtypes. Radioligand binding studies showed that alpha(1)-AR binding capacity in the aorta was lost, while that in the heart was unaltered in alpha(1D)-/- mice. Non-anesthetized alpha(1D)-/- mice maintained significantly lower basal systolic and mean arterial blood pressure conditions, relative to wild-type mice, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. Besides hypotension, the pressor responses to phenylephrine and norepinephrine were decreased by 30-40% in alpha(1D)-/- mice. Furthermore, the contractile response of the aorta and the pressor response of isolated perfused mesenteric arterial beds to alpha(1)-AR stimulation were markedly reduced in alpha(1D)-/- mice. We conclude that the alpha(1D)-AR participates directly in sympathetic regulation of systemic blood pressure by vasoconstriction.