Enhanced sympathetic outflow is seen in both patients with
congestive heart failure and animals with experimental
heart failure. In a previous study, we demonstrated that the baroreflex control of heart rate was impaired in conscious rabbits with pacing-induced
heart failure and that this impairment was partially restored by blockade of
angiotensin II type 1 (AT1) receptors. In the present study, we determined the interaction between the renin-angiotensin system and baroreflex control of renal sympathetic nerve activity in normal conscious rabbits and conscious rabbits with pacing-induced
heart failure before and after AT1 receptor blockade.
Heart failure was induced by rapid ventricular pacing at a rate of 360 to 380 beats per minute for an average of 16.7 +/- 0.6 days. To generate baroreflex curves, we altered arterial pressure by administering
phenylephrine and
sodium nitroprusside. A sigmoidal logistic function was fit to renal sympathetic nerve activity-mean arterial pressure relationships for analysis of several components of baroreflex function. AT1 receptors were blocked by
intravenous administration of the specific antagonist
L-158,809. In normal rabbits, there was no significant difference in any parameter of baroreflex function before and after blockade of AT1 receptors. In contrast, blockade of AT1 receptors enhanced baroreflex sensitivity in
heart failure rabbits. The maximal gain increased to 5.0 +/- 0.7% renal sympathetic nerve activity/mm Hg from 2.6 +/- 0.3 (P < .05). Although
L-158,809 had no effect on baseline renal sympathetic nerve activity in normal rabbits, analysis of the data in the
heart failure rabbits indicated that baseline renal sympathetic nerve activity was reduced from 33 +/- 5% to 17 +/- 4% after
L-158,809 administration after adjustment for changes in arterial pressure. These data suggest that
angiotensin II plays a role in baroreflex impairment in this model of
heart failure and may be in part responsible for the depressed baroreflex sensitivity observed in
heart failure.