5-HT1A Receptors of the Nucleus Tractus Solitarii Facilitate Sympathetic Recovery Following Hypotensive Hemorrhage in Rats Journal Article

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Authors: Vantrease, J. E.; Dudek, N.; DonCarlos, L. L.; Scrogin, K. E.
Article Title: 5-HT1A Receptors of the Nucleus Tractus Solitarii Facilitate Sympathetic Recovery Following Hypotensive Hemorrhage in Rats
Abstract: The role of serotonin in the hemodynamic response to blood loss remains controversial. Caudal raphe serotonin neurons are activated during hypotensive hemorrhage, and their destruction attenuates sympathetic increases following blood loss in unanesthetized rats. Caudal raphe neurons provide serotonin-positive projections to the nucleus tractus solitarii (NTS), and disruption of serotonin-positive nerve terminals in the NTS attenuates sympathetic recovery following hemorrhage. Administration of 5-HT1A receptor agonists following hemorrhage augments sympathetic-mediated increases in venous tone and tissue hypoxia. These findings led us to hypothesize that severe blood loss promotes activation of 5-HT1A receptors in the NTS which facilitates sympathetic recovery and peripheral tissue perfusion. Here, we developed an adeno-associated viral vector encoding an efficacious shRNA sequence targeting the rat 5-HT1A receptor. Unanesthetized rats subjected to NTS injection of the anti-rat 5-HT1A shRNA-encoding vector 4 weeks prior showed normal blood pressure recovery, but an attenuated recovery of renal sympathetic nerve activity (-6.4 +/- 12.9 vs. 42.6 +/- 15.6 %baseline, P0.05) 50 minutes after 21% estimated blood volume withdrawal. The same rats developed increased tissue hypoxia after hemorrhage as indicated by a prolonged elevations in lactate (2.77 +/- 0.5 vs 1.34 +/- 0.2 mmol/L, 60 min after start of hemorrhage, P0.05). 5-HT1A mRNA levels in the commissural NTS were directly correlated with renal sympathetic nerve activity (P0.01) and inversely correlated with lactate (P0.05) 60 minutes after start of hemorrhage. The data suggest that 5-HT1A receptors in the commissural NTS facilitate tissue perfusion after blood loss likely by increasing sympathetic-mediated venous return.
Journal Title: American journal of physiology.Heart and circulatory physiology
ISSN: 1522-1539; 0363-6135
Publisher: American Journal of Physiology - Heart and Circulatory Physiology  
Date Published: 2015
Start Page: ajpheart.00117.2015
Language: ENG
DOI/URL:

10.1152/ajpheart.00117.2015
Notes: LR: 20150519; CI: Copyright (c) 2015; JID: 100901228; OTO: NOTNLM; aheadofprint; SO: Am J Physiol Heart Circ Physiol. 2015 May 15:ajpheart.00117.2015. doi: 10.1152/ajpheart.00117.2015.