TY - JOUR
T1 - Activation of 5-hydroxytryptamine-1A receptors suppresses cardiovascular responses evoked from the paraventricular nucleus
AU - Horiuchi, Jouji
AU - Atik, Alp
AU - Iigaya, Kamon
AU - McDowall, Lachlan M.
AU - Killinger, Suzanne
AU - Dampney, Roger A L
PY - 2011/10
Y1 - 2011/10
N2 - Activation of central 5-hydroxytryptamine-1A (5-HT 1A) receptors powerfully inhibits stress-evoked cardiovascular responses mediated by the dorsomedial hypothalamus (DMH), as well as responses evoked by direct activation of neurons within the DMH. The hypothalamic paraventricular nucleus (PVN) also has a crucial role in cardiovascular regulation and is believed to regulate heart rate and renal sympathetic activity via pathways that are independent of the DMH. In this study, we determined whether cardiovascular responses evoked from the PVN are also modulated by activation of central 5-HT 1A receptors. In anesthetized rats, the increases in heart rate and renal sympathetic nerve activity evoked by bicuculline injection into the PVN were greatly reduced (by 54% and 61%, respectively) by intravenous administration of (±)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), an agonist of 5-HT 1A receptors, but were then completely restored by subsequent administration of WAY-100635, a selective antagonist of 5-HT 1A receptors. Microinjection of 8-OH-DPAT directly into the PVN did not significantly affect the responses to bicuculline injection into the PVN, nor did systemic administration of WAY-100635 alone. In control experiments, a large renal sympathoexcitatory response was evoked from both the PVN and DMH but not from the intermediate region in between; thus the evoked responses from the PVN were not due to activation of neurons in the DMH. The results indicate that activation of central 5-HT 1A receptors located outside the PVN powerfully inhibits the tachycardia and renal sympathoexcitation evoked by stimulation of neurons in the PVN.
AB - Activation of central 5-hydroxytryptamine-1A (5-HT 1A) receptors powerfully inhibits stress-evoked cardiovascular responses mediated by the dorsomedial hypothalamus (DMH), as well as responses evoked by direct activation of neurons within the DMH. The hypothalamic paraventricular nucleus (PVN) also has a crucial role in cardiovascular regulation and is believed to regulate heart rate and renal sympathetic activity via pathways that are independent of the DMH. In this study, we determined whether cardiovascular responses evoked from the PVN are also modulated by activation of central 5-HT 1A receptors. In anesthetized rats, the increases in heart rate and renal sympathetic nerve activity evoked by bicuculline injection into the PVN were greatly reduced (by 54% and 61%, respectively) by intravenous administration of (±)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), an agonist of 5-HT 1A receptors, but were then completely restored by subsequent administration of WAY-100635, a selective antagonist of 5-HT 1A receptors. Microinjection of 8-OH-DPAT directly into the PVN did not significantly affect the responses to bicuculline injection into the PVN, nor did systemic administration of WAY-100635 alone. In control experiments, a large renal sympathoexcitatory response was evoked from both the PVN and DMH but not from the intermediate region in between; thus the evoked responses from the PVN were not due to activation of neurons in the DMH. The results indicate that activation of central 5-HT 1A receptors located outside the PVN powerfully inhibits the tachycardia and renal sympathoexcitation evoked by stimulation of neurons in the PVN.
KW - Blood pressure
KW - Dorsomedial hypothalamus
KW - Heart rate
KW - Renal sympathetic activity
UR - http://www.scopus.com/inward/record.url?scp=80053628008&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00144.2011
DO - 10.1152/ajpregu.00144.2011
M3 - Article
C2 - 21753144
AN - SCOPUS:80053628008
SN - 0363-6119
VL - 301
SP - R1088-R1097
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 4
ER -