Functional response to cardiac sympathetic activation in transgenic
mice overexpressing b2-adrenergic receptor.
Du, Xiao-Jun, Elizabeth Vincan, David M Woodcock, Carmelo A. Milano,
Anthony M Dart, Elizabeth A. Woodcock.
Baker Medical Research Institute, Melbourne, Australia, Molecular
Genetics Laboratory, Peter MacCallum Cancer Research Institute,
Melbourne, Australia, Howard Hughes Medical Institute Research
Laboratories, Duke University Medical Center, Durham, North Carolina,
USA
APStracts 3:0071H, 1996.
Transgenic mice have been created with 200 fold overexpression of b2
-adrenergic receptors specifically in the heart. Cardiac function was
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
left ventricle dP/dtmax and heart rate (HR) were measured. Basal HR
and dP/dtmax were 30 to 40% higher in hearts from transgenic mice
than controls. Electrical stimulation of sympathetic nerves (2, 4 and
8 Hz) or infusion of isoproterenol markedly increased HR and dP/dtmax
in control hearts. Hearts from transgenic mice did not respond to
isoproterenol. However, hearts from transgenic mice retained the HR
response to nerve stimulation and a small increase in dP/dtmax was
also detected. Atenolol inhibited the response to nerve stimulation
in control hearts but not that in hearts from transgenic mice. ICI
118551 inhibited the response in transgenic hearts. Basal HR and
dP/dtmax were decreased by ICI 118551 only in transgenic hearts.
Thus, overexpression of cardiac b2-receptors modifies b-adrenergic
activity but the responses to endogenous and exogenous adrenergic
stimulation are affected differently.
Received 19 October 1995; accepted in final form 23 January 1996.
APS Manuscript Number H977-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96