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

点击翻译按钮获取中文摘要

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.