PT - JOURNAL ARTICLE AU - Chihiro Hosoda AU - Taka-aki Koshimizu AU - Akito Tanoue AU - Yoshihisa Nasa AU - Ryo Oikawa AU - Takashi Tomabechi AU - Shinya Fukuda AU - Hitomi Shinoura AU - Sayuri Oshikawa AU - Satoshi Takeo AU - Tadaichi Kitamura AU - Susanna Cotecchia AU - Gozoh Tsujimoto TI - Two α<sub>1</sub>-Adrenergic Receptor Subtypes Regulating the Vasopressor Response Have Differential Roles in Blood Pressure Regulation AID - 10.1124/mol.104.007500 DP - 2005 Mar 01 TA - Molecular Pharmacology PG - 912--922 VI - 67 IP - 3 4099 - http://molpharm.aspetjournals.org/content/67/3/912.short 4100 - http://molpharm.aspetjournals.org/content/67/3/912.full SO - Mol Pharmacol2005 Mar 01; 67 AB - To study the functional role of individual α1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the α1B-AR and/or α1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the α1D-AR knockout and α1B-/α1D-AR double knockout mice, but not the α1B-AR knockout mice, had significantly (p &lt; 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 &lt; 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 α1B-/α1D-AR double knockout mice. In an attempt to further examine α1-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, α1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking α1D-AR had significantly (p &lt; 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that α1B- and α1D-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional α1D-AR, not α1B-AR, leads to an antihypertensive effect. The study shows differential contributions of α1B- and α1D-ARs in BP regulation.