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Am J Physiol Heart Circ Physiol 277: H342-H350, 1999;
0363-6135/99 $5.00
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Vol. 277, Issue 1, H342-H350, July 1999

ANG II and baroreflex function in rabbits with CHF and lesions of the area postrema

Jun-Li Liu1, Hiroshi Murakami1, Max Sanderford2, Vernon S. Bishop2, and Irving H. Zucker1

1 Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha, Nebraska 68198; and 2 University of Texas Health Sciences Center at San Antonio, San Antonio, Texas 78284

Blockade of the angiotensin II (ANG II) type 1 receptor (AT1) has been shown to restore baroreflex sensitivity in rats and rabbits with experimental chronic heart failure (CHF). Because the modulation of baroreflex function in response to ANG II is mediated in part by AT1 receptors located in the area postrema, we hypothesized that lesions of the area postrema would prevent the enhancement in baroreflex function in response to AT1-receptor blockade in rabbits with pacing-induced CHF. Experiments were carried out on 24 male New Zealand White rabbits that were divided into sham (n = 12) and lesioned (n = 12) groups further divided into normal and CHF subgroups (n = 6 each). All rabbits were identically instrumented to measure cardiac external dimensions, central venous pressure, arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA). After 3-4 wk of pacing, baroreflex sensitivity (infusions of phenylephrine and nitroprusside) was evaluated before and after intravenous administration of the AT1-receptor antagonist L-158,809. Maximum baroreflex sensitivity in nonpaced rabbits was 5.4 ± 0.7 beats · min-1 · mmHg-1 and 5.2 ± 0.5% of maximum/mmHg for HR and RSNA curves, respectively, and was not altered by L-158,809 in either intact or lesioned rabbits. In contrast, L-158,809 enhanced baroreflex sensitivity in intact rabbits with CHF (HR from 1.6 ± 0.3 to 4.1 ± 0.7 beats · min-1 · mmHg-1, P < 0.001; RSNA from 2.3 ± 0.2 to 4.9 ± 0.4% of maximum/mmHg, P < 0.001). However, in CHF rabbits with area postrema lesions, L-158,809 failed to enhance baroreflex sensitivity. Interestingly, area postrema lesions did not normalize the baroreflex in CHF rabbits. From these data we conclude that the area postrema mediates the normalization of baroreflex sensitivity after AT1 blockade in rabbits with CHF but does not modify resting baroreflex function.

angiotensin II; angiotensin receptors; experimental heart failure; central nervous system; sympathetic nerve activity


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