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Vol. 60, Issue 5, 955-962, November 2001
-Adrenergic Receptor Subtypes in
Blood Vessels of Knockout Mice Lacking 1- or
2-Adrenergic Receptors
Howard Hughes Medical Institute, Stanford University, Stanford,
California (A.C., B.K.K.); and Department of Pharmacology, University
of Würzburg, Würzburg, Germany (M.E.B., L.M., M.J.L., L.H.)
-Adrenergic receptors (-AR) are essential regulators of
cardiovascular homeostasis. In addition to their prominent function in
the heart, -AR are located on vascular smooth muscle cells, where
they mediate vasodilating effects of endogenous catecholamines. In this
study, we have investigated in an isometric myograph different types of
blood vessels from mice lacking 1- and/or
2-adrenergic receptor subtypes (1-KO,
2-KO, 12-KO). In wild-type
mice, isoproterenol induced relaxation of segments from thoracic aorta, carotid, femoral and pulmonary arteries, and portal vein. The relaxant
effect of -receptor stimulation was absent in femoral and pulmonary
arteries from 1-KO mice. In aortic and carotid arteries
and in portal veins, the vasodilating effect of isoproterenol was
reduced in mice lacking 1- or
2-receptors. However, in these vessels the vasodilating
effect was only abolished in double KO mice lacking both
1- and 2-receptors. Vessel relaxation
induced by forskolin did not differ between wild-type and KO mice.
Similar contributions of 1- and
2-receptors to isoproterenol-induced vasorelaxation were
found when vessels from KO mice were compared with wild-type arteries
in the presence of subtype-selective -receptor antagonists. These
studies demonstrate that 1-adrenergic receptors play a
dominant role in the murine vascular system to mediate vasodilation.
Surprisingly, 2-receptors contribute to adrenergic vasodilation only in a few major blood vessels, suggesting that differential distribution of -adrenergic receptor subtypes may play
an important role in redirection of tissue perfusion.
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