Received for publication September 22, 2004.
Revised December 13, 2004.
Accepted for publication December 14, 2004.

Two ₁-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation

Abstract

To study the functional role of individual ₁-adrenergic receptor (₁-AR) subtypes in blood pressure (BP) regulation, we used mice with the same genetic background that were lacking the _1B-AR and/or _1D-AR, and we also studied their hemodynamic and vasocontractile responses. Both the _1D-AR knockout and _1B-/_1D-AR double knockout, but not the _1B-AR knockout mice, had significantly (p <0.05) lower levels of basal systolic and mean arterial BP than did wild type mice. The mice were not anesthetized, and they showed no significant changes in heart rate (HR) or in cardiac function, as assessed by echocardiogram. All mutants showed significantly significantly (p <0.05) reduced catecholamine-induced pressor and vasoconstriction responses. Notably, the infusion of norepinephrine did not elicit any pressor response at all in _1B-/_1D-AR double knockout mice. In an attempt to further examine which ₁-AR subtype is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the end point by direct intra-arterial recording. After salt-loading, _1B-AR knockout mice developed a comparable level of hypertension to wild type mice, while mice lacking _1D-AR had significantly significantly (p <0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that _1B- and _1D-AR subtypes participate cooperatively in BP regulation; however, deletion of the functional _1D-AR, but not _1B-AR, leads to an anti-hypertensive effect. This study therefore demonstrates the differential contributions of _1B- and _1D-ARs to BP regulation.

Key words: Adrenergic, Gq/11 family, Func. analysis receptor/ion channel mutants, Knockout

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