TY - JOUR T1 - The Serotonin 5-Hydroxytryptaphan<sub>1A</sub> Receptor Agonist, (+)8-Hydroxy-2-(di-<em>n</em>-propylamino)-tetralin, Stimulates Sympathetic-Dependent Increases in Venous Tone during Hypovolemic Shock JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 776 LP - 782 DO - 10.1124/jpet.106.108944 VL - 319 IS - 2 AU - Ruslan Tiniakov AU - Karie E. Scrogin Y1 - 2006/11/01 UR - http://jpet.aspetjournals.org/content/319/2/776.abstract N2 - Adjuvant treatment of hypovolemic shock with vasoconstrictors is controversial due to their propensity to raise arterial resistance and exacerbate ischemia. A more advantageous therapeutic approach would use agents that also promote venoconstriction to augment perfusion pressure through increased venous return. Recent studies indicate that 5-hydroxytryptophan (5-HT)1A receptor agonists increase blood pressure by stimulating sympathetic drive when administered after acute hypotensive hemorrhage. Given that venous tone is highly dependent upon sympathetic activation of α2-adrenergic receptors, we hypothesized that the 5-HT1A receptor agonist, (+)8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), would increase venous tone in rats subject to hypovolemic shock through sympathetic activation of α2-adrenergic receptors. Systemic administration of 8-OH-DPAT produced a sustained rise in blood pressure (+44 ± 3 mm Hg 35 min after injection, P &lt; 0.01 versus saline) and mean circulatory filling pressure (+4.2 ± 0.7 mm Hg, P &lt; 0.01 versus saline) in conscious rats subjected to hypovolemic shock. An equipressor infusion of epinephrine failed to influence mean circulatory filling pressure (MCFP). Ganglionic blockade, α1-, or peripheral α2-adrenergic receptor blockade prevented the rise in MCFP observed with 8-OH-DPAT, but only α1-adrenergic receptor blockade diminished the pressor effect of the drug (P &lt; 0.01). 8-OH-DPAT raises blood pressure in rats in hypovolemic shock through both direct vascular activation and sympathetic activation of α1-adrenergic receptors. The sympathoexcitatory effect of 8-OH-DPAT contributes to elevated venous tone through concurrent activation of both α1- and α2-adrenergic receptors. The data suggest that 5-HT1A receptor agonists may provide an advantageous alternative to currently therapeutic interventions used to raise perfusion pressure in hypovolemic shock. The American Society for Pharmacology and Experimental Therapeutics ER -