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1573679 
Journal Article 
Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure 
Xu, Bo; Zheng, H; Patel, KP 
2012 
Yes 
American Journal of Physiology: Heart and Circulatory Physiology
ISSN: 0363-6135
EISSN: 1522-1539 
302 
8 
H1700-H1711 
22307669 
WOS:000302911500015 
Xu B, Zheng H, Patel KP. Enhanced activation of RVLM projecting PVN neurons in rats with chronic heart failure. Am J Physiol Heart Circ Physiol 302:
H1700-H1711, 2012. First published February 3, 2012; doi: 10.1152/ajpheart.00722.2011.-Previous
studies have indicated that there is increased activation of the paraventricular nucleus (PVN) in
rats with chronic heart failure (CHF); however, it is not clear if the preautonomic neurons
within the PVN are specifically overactive. Also, it is not known if these neurons have altered
responses to baroreceptor or osmotic challenges. Experiments were conducted in rats with CHF (6-8
wk after coronary artery ligation). Spontaneously active neurons were recorded in the PVN, of
which 36% were antidromically activated from the rostral ventrolateral medulla (RVLM). The
baseline discharge rate in RVLM-projecting PVN (PVN-RVLM) neurons from CHF rats was significantly
greater than in sham-operated (sham) rats (6.0 +/- 0.6 vs. 2.6 +/- 0.3 spikes/s, P < 0.05).
Picoinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist D, L-2-amino-5-
phosphonovaleric acid significantly decreased the basal discharge of PVN-RVLM neurons by 80% in
CHF rats compared with 37% in sham rats. Fifty-two percent of spontaneously active PVN-RVLM
neurons responded to changes in the mean arterial pressure (MAP). The changes in discharge rate
in PVN-RVLM neurons after a reduction in MAP (+52 +/- 7% vs. +184 +/- 61%) or an increase in MAP
(-42 +/- 8% vs. -71 +/- 6%) were significantly attenuated in rats with CHF compared with sham
rats. Most PVN-RVLM neurons (63%), including all barosensitive PVN-RVLM neurons, were excited by
an internal carotid artery injection of hypertonic NaCl (2.1 osmol/l), whereas a smaller number
(7%) were inhibited. The increase in discharge rate in PVN-RVLM neurons to hypertonic stimulation
was significantly enhanced in rats with CHF compared with sham rats (134 +/- 15% vs. 92 +/- 13%).
Taken together, these data suggest that PVN-RVLM neurons are more active under basal conditions
and this overactivation is mediated by an enhanced glutamatergic tone in rats with CHF.
Furthermore, this enhanced activation of PVN-RVLM neurons may contribute to the altered responses
to baroreceptor and osmotic challenges observed during CHF. 
paraventricular nucleus; rostral ventrolateral medulla; sympathetic activity; baroreflex; osmotic challenge