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  • Title: Blockade of AT1 receptors enhances baroreflex control of heart rate in conscious rabbits with heart failure.
    Author: Murakami H, Liu JL, Zucker IH.
    Journal: Am J Physiol; 1996 Jul; 271(1 Pt 2):R303-9. PubMed ID: 8760234.
    Abstract:
    Because the renin-angiotensin system is activated in heart failure, we hypothesized that angiotensin II (ANG II) 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 beats/min for an average of 14.5 +/- 1.4 days. The data were compared with 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 intravenous administration of the AT1 antagonist L-158,809. Rabbits with heart failure exhibited significantly lower arterial pressure (81 +/- 3 vs. 69 +/- 4 mmHg, P < 0.05), elevated resting HR (230 +/- 5 vs. 260 +/- 10 beats/min, P < 0.05), and elevated left atrial pressure (3.6 +/- 0.7 vs. 13.1 +/- 0.7 mmHg, P < 0.05). ANG II 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 beats.min-1.mmHg-1; P < 0.05), primarily by increasing the minimum HR evoked during baroreceptor activation. beta 1-Blockade had no effect on any baroreflex parameter after L-158,809 in rabbits with heart failure. However, L-158,809 significantly reduced the minimum HR after pretreatment with atropine in rabbits with heart failure. These data suggest that ANG II 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.
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