Document Detail

Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock.
MedLine Citation:
PMID:  22718805     Owner:  NLM     Status:  MEDLINE    
Administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT, improves cardiovascular hemodynamics and tissue oxygenation in conscious rats subjected to hypovolemic shock. This effect is mediated by sympathetic-dependent increases in venous tone. To determine the role of splanchnic nerves in this response, effects of 8-OH-DPAT (30 nmol/kg iv) were measured following fixed-arterial blood pressure hemorrhagic shock (i.e., maintenance of 50 mmHg arterial pressure for 25 min) in rats subjected to bilateral splanchnic nerve denervation (SD). Splanchnic denervation decreased baseline venous tone as measured by mean circulatory filling pressure (MCFP) and accelerated the onset of hypotension during blood loss. Splanchnic denervation did not affect the immediate pressor effect of 8-OH-DPAT but did reverse the drug's lasting pressor effect, as well as its ability to increase MCFP and improve metabolic acidosis. Like SD, adrenal demedullation (ADMX) lowered baseline MCFP and accelerated the hypotensive response to blood withdrawal but also reduced the volume of blood withdrawal required to maintain arterial blood pressure at 50 mmHg. 8-OH-DPAT raised MCFP early after administration in ADMX rats, but the response did not persist throughout the posthemorrhage period. In a fixed-volume hemorrhage model, 8-OH-DPAT continued to raise blood pressure in ADMX rats. However, it produced only a transient and variable rise in MCFP compared with sham-operated animals. The data indicate that 8-OH-DPAT increases venoconstriction and improves acid-base balance in hypovolemic rats through activation of splanchnic nerves. This effect is due, in part, to activation of the adrenal medulla.
Ruslan Tiniakov; Kalipada Pahan; Karie E Scrogin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-20
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  303     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-03     Completed Date:  2012-11-20     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R527-38     Citation Subset:  IM    
Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Stritch School of Medicine, Chicago, IL, USA.
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MeSH Terms
8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
Acid-Base Equilibrium / drug effects,  physiology
Adrenal Medulla / innervation,  physiology,  surgery
Blood Pressure / drug effects,  physiology
Hemodynamics / drug effects*,  physiology
Models, Animal
Rats, Sprague-Dawley
Serotonin Receptor Agonists / pharmacology*
Shock, Hemorrhagic / physiopathology*
Splanchnic Nerves / physiology*,  surgery
Sympathetic Nervous System / physiology*,  surgery
Vasoconstriction / drug effects,  physiology
Grant Support
Reg. No./Substance:
0/Serotonin Receptor Agonists; 78950-78-4/8-Hydroxy-2-(di-n-propylamino)tetralin

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