Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock

Am J Physiol Regul Integr Comp Physiol. 2012 Sep 1;303(5):R527-38. doi: 10.1152/ajpregu.00689.2011. Epub 2012 Jun 20.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Acid-Base Equilibrium / drug effects
  • Acid-Base Equilibrium / physiology
  • Adrenal Medulla / innervation
  • Adrenal Medulla / physiology
  • Adrenal Medulla / surgery
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Hemodynamics / drug effects*
  • Hemodynamics / physiology
  • Male
  • Models, Animal
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Receptor Agonists / pharmacology*
  • Shock, Hemorrhagic / physiopathology*
  • Splanchnic Nerves / physiology*
  • Splanchnic Nerves / surgery
  • Sympathectomy
  • Sympathetic Nervous System / physiology*
  • Sympathetic Nervous System / surgery
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology


  • Serotonin Receptor Agonists
  • 8-Hydroxy-2-(di-n-propylamino)tetralin