Analysis of cardiovascular function with mutant mice lacking for single or multiple alpha 1 adrenergic receptor.

为了研究单个α 1-肾上腺素能（AR）亚型在血压（BP）调节中的功能作用，我们使用具有相同遗传背景的缺乏α 1b -AR和/或α 1d -AR的小鼠，进一步研究其血流动力学和血管收缩反应。在非麻醉状态下，alpha1B- ar敲除小鼠和alpha1B-/alpha1D-AR双敲除小鼠的基础收缩压和平均动脉血压水平均显著低于野生型小鼠（p < 0.05），超声心动图显示，它们的心率和心功能没有明显变化。此外，三种亚型的三重敲除显示血压降低。所有突变体均显示儿茶酚胺诱导的压力和血管收缩反应显著（p < 0.05）降低。值得注意的是，在alpha1B-/alpha1D-AR双敲除小鼠中，输注去甲肾上腺素完全没有引起任何升压反应。为了进一步研究参与高血压发生或维持的α - 1- ar亚型，通过尾袖带读数监测盐负荷后的血压，并在终点通过直接动脉内记录确认。盐负荷后，α 1b - ar基因敲除小鼠的高血压水平与野生型小鼠相当，而缺乏α 1b - ar基因敲除小鼠的血压显著（p < 0.05）降低，循环儿茶酚胺水平较低。我们的数据表明，alpha1b和alpha1D-AR亚型协同参与血压调节；然而，功能性α 1d - ar的缺失，而不是α 1b - ar的缺失，导致降压作用。该研究显示了alpha1b和alpha1D-ARs在血压调节中的不同贡献。

To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1B-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1A-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in non-anesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. Furthermore, triple knockout of three subtypes showed reduced blood pressure. All mutants showed a significantly (p < 0.05) reduced catecholamine-induced pressor and vasoconstriction responses. It is noteworthy that the infusion of norepinephrine did not elicit any pressor response at all in alpha1B-/alpha1D-AR double knockout mice. In an attempt to further examine alpha1-AR subtype, which is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the endpoint by direct intra-arterial recording. After salt loading, alpha1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha1D-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha1B-and alpha1D-AR subtypes participate cooperatively in BP regulation ; however, the deletion of the functional alpha1D-AR, not alpha1B-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha1B-and alpha1D-ARs in BP regulation.