Abstract

β-Adrenergic receptors (β-AR) are essential regulators of cardiovascular homeostasis. In addition to their prominent function in the heart, β-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 β₁- and/or β₂-adrenergic receptor subtypes (β₁-KO, β₂-KO, β₁β₂-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 β-receptor stimulation was absent in femoral and pulmonary arteries from β₁-KO mice. In aortic and carotid arteries and in portal veins, the vasodilating effect of isoproterenol was reduced in mice lacking β₁- or β₂-receptors. However, in these vessels the vasodilating effect was only abolished in double KO mice lacking both β₁- and β₂-receptors. Vessel relaxation induced by forskolin did not differ between wild-type and KO mice. Similar contributions of β₁- and β₂-receptors to isoproterenol-induced vasorelaxation were found when vessels from KO mice were compared with wild-type arteries in the presence of subtype-selective β-receptor antagonists. These studies demonstrate that β₁-adrenergic receptors play a dominant role in the murine vascular system to mediate vasodilation. Surprisingly, β₂-receptors contribute to adrenergic vasodilation only in a few major blood vessels, suggesting that differential distribution of β-adrenergic receptor subtypes may play an important role in redirection of tissue perfusion.