Differential distribution of beta-adrenergic receptor subtypes in blood vessels of knockout mice lacking beta(1)- or beta(2)-adrenergic receptors

beta -Adrenergic receptors (beta -AR) are essential regulators of cardiovas cular homeostasis. In addition to their prominent function in the heart, be ta -AR are located on vascular smooth muscle cells, where they mediate vaso dilating effects of endogenous catecholamines. In this study, we have inves tigated in an isometric myograph different types of blood vessels from mice lacking beta (1)- and/or beta (2)-adrenergic receptor subtypes (beta (1)-K O, beta (2)-KO, beta (1)beta (2)-KO). In wild-type mice, isoproterenol indu ced relaxation of segments from thoracic aorta, carotid, femoral and pulmon ary arteries, and portal vein. The relaxant effect of beta -receptor stimul ation was absent in femoral and pulmonary arteries from beta (1)-KO mice. I n aortic and carotid arteries and in portal veins, the vasodilating effect of isoproterenol was reduced in mice lacking beta (1)- or beta (2)-receptor s. However, in these vessels the vasodilating effect was only abolished in double KO mice lacking both beta1- and beta (2)-receptors. Vessel relaxatio n induced by forskolin did not differ between wild-type and KO mice. Simila r contributions of beta (1)- and beta (2)-receptors to isoproterenol-induce d vasorelaxation were found when vessels from KO mice were compared with wi ld-type arteries in the presence of subtype-selective beta -receptor antago nists. These studies demonstrate that beta (1)-adrenergic receptors play a dominant role in the murine vascular system to mediate vasodilation. Surpri singly, beta (2)-receptors contribute to adrenergic vasodilation only in a few major blood vessels, suggesting that differential distribution of beta -adrenergic receptor subtypes may play an important role in redirection of tissue perfusion.