Blockade of angiotensin-1 receptors enhances baroreflex control of
heart rate in conscious rabbits with heart failure.
Murakami, Hiroshi, Jun-Li Liu, and Irving H. Zucker.
Department of Physiology and Biophysics, University of Nebraska
College of Medicine, Omaha, Ne. 68198-4575
APStracts 3:0062R, 1996.
Because the renin-angiotensin (AII) system is activated in heart
failure we hypothesized that AII plays a role in altering baroreflex
sensitivity in the setting of heart failure. Accordingly we evaluated
the baroreflex control of heart rate (HR) in conscious, chronically
instrumented rabbits in the normal state and after the establishment
of heart failure. Heart failure was induced by rapid ventricular
pacing at a rate of 360-380 bpm for an average of 14.5+/-1.4 days.
The data were compared to normal rabbits instrumented in a similar
fashion. Baroreflex curves were generated by inflation of implanted
hydraulic occluders on the vena cava and aortic arch or by
administration of phenylephrine and sodium nitroprusside. Experiments
were carried out before and after i.v. administration of the AT1
antagonist L-158,809. Rabbits with heart failure exhibited
significantly lower arterial pressure (81+/-3 vs. 69+/-4 mm Hg,
p<.05), elevated resting HR (230+/-5 vs. 260+/-10 bpm,
p<.05) and elevated left atrial pressure (3.6+/-0.7 vs. 13.1+/
-0.7 mm Hg, p<.05). AII blockade had little effect on resting or
baroreflex parameters in normal rabbits. However, in rabbits with
heart failure, L-158,809 enhanced baroreflex sensitivity (2.7+/-0.5
vs. 4.7+/-0.8 bpm/mmHg; p<.05) primarily by increasing the
minimum HR evoked during baroreceptor activation. [beta]1 blockade
had no effect on any baroreflex parameter following L-158,809 in
rabbits with heart failure. However, L-158,809 significantly reduced
the minimum HR following pre-treatment with atropine in rabbits with
heart failure. These data suggest that AII plays a role in modulation
of cardiac sympathetic tone in this model of heart failure and may be
responsible for the depressed baroreflex sensitivity observed in
heart failure.
Received 6 November 1995; accepted in final form 15 February
1996.
APS Manuscript Number R687-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96