Two α1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation

To study the functional role of individual alpha(1)-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha(1B)-AR and/or alpha(1D)-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha(1D)-AR knockout and alpha(1B)-/- alpha(1D)-AR double knockout mice, but not the alpha(1B)-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. 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 alpha(1B)-/alpha(1D)-AR double knockout mice. In an attempt to further examine alpha(1)-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, alpha(1B)-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha(1D)-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha(1B)- and alpha(1D)-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional alpha(1D)-AR, not alpha(1B)-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha(1B)- and alpha(1D)-ARs in BP regulation.