Xj. Du et al., RESPONSE TO CARDIAC SYMPATHETIC ACTIVATION IN TRANSGENIC MICE OVEREXPRESSING BETA(2)-ADRENERGIC RECEPTOR, American journal of physiology. Heart and circulatory physiology, 40(2), 1996, pp. 630-636
Transgenic mice have been created with 200-fold overexpression of beta
(2)-adrenergic receptors specifically in the heart. Cardiac function w
as studied in these transgenic mice and their controls at baseline and
during isoproterenol perfusion or sympathetic nerve stimulation. The
model used was an in situ buffer-perfused, innervated heart, and the l
eft ventricle maximal derivative of pressure over time (dP/dt(max)) an
d heart rate (HR) were measured. Basal HR and dP/dt(max) were 30-40% h
igher in hearts from transgenic mice than controls. Electrical stimula
tion of sympathetic nerves (2, 4, and 8 Hz) or infusion of isoproteren
ol markedly increased HR and dP/dt(max) in control hearts. Hearts from
transgenic mice did not respond to isoproterenol. However, hearts fro
m transgenic mice retained the HR response to nerve stimulation, and a
small increase in dP/dt(max) was also detected. Atenolol inhibited th
e response to nerve stimulation in control hearts but not that in hear
ts from transgenic mice. ICI-118551 inhibited the response in transgen
ic hearts. Basal HR and dP/dt(max) were decreased by ICI-118551 only i
n transgenic hearts. Thus overexpression of cardiac beta(2)-receptors
modifies beta-adrenergic activity, but the responses to endogenous and
exogenous adrenergic stimulation are affected differently.