[Adrenergic receptor and knockout mouse: 1) Beta adrenergic receptor knockout mouse]

Abstract

Functional analysis of beta 1 and beta 2 adrenergic receptor (AR) subtypes has been made possible by establishing knockout mice (KO) with abolished beta 1 and/or beta 2 AR expression. Neither resting heart rate nor resting blood pressure of beta 1 AR KO, beta 2 AR KO, or beta 1/beta 2 KO differed significantly from those of wild-type mice. The chronotropic response to isoproterenol was significantly attenuated in beta 1 AR KO and beta 1/beta 2 KO, whereas there was no detrimental effect on heart rate in beta 2 AR KO. This suggests that chronotropy is mediated by beta 1 AR. In terms of the vasodilatory response to isoproterenol, there appears to be a graded and additive attenuation of the hypotensive response in beta 1 AR KO, beta 2 AR KO, and beta 1/beta 2 KO. Vascular relaxation is thought to be controlled by both beta 1 AR and beta 2 AR. Tachycardia induced by exercise was significantly attenuated in beta 1 AR KO, and beta 1/beta 2 KO. beta 2 AR KO subjected to treadmill exercise showed significant hypertension, increased oxygen consumption, and ability of long distance running.