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CARDIOVASCULAR

The Serotonin 5-Hydroxytryptaphan_1A Receptor Agonist, (+)8-Hydroxy-2-(di-n-propylamino)-tetralin, Stimulates Sympathetic-Dependent Increases in Venous Tone during Hypovolemic Shock

Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Chicago, Illinois

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 ₂-adrenergic receptors, we hypothesized that the 5-HT_1A 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 ₂-adrenergic receptors. Systemic administration of 8-OH-DPAT produced a sustained rise in blood pressure (+44 ± 3 mm Hg 35 min after injection, P < 0.01 versus saline) and mean circulatory filling pressure (+4.2 ± 0.7 mm Hg, P < 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, ₁-, or peripheral ₂-adrenergic receptor blockade prevented the rise in MCFP observed with 8-OH-DPAT, but only ₁-adrenergic receptor blockade diminished the pressor effect of the drug (P < 0.01). 8-OH-DPAT raises blood pressure in rats in hypovolemic shock through both direct vascular activation and sympathetic activation of ₁-adrenergic receptors. The sympathoexcitatory effect of 8-OH-DPAT contributes to elevated venous tone through concurrent activation of both ₁- and ₂-adrenergic receptors. The data suggest that 5-HT_1A receptor agonists may provide an advantageous alternative to currently therapeutic interventions used to raise perfusion pressure in hypovolemic shock.

Address correspondence to: Dr. Karie Scrogin, Department of Pharmacology, 2160 South First Avenue, Maywood, IL 60153. E-mail: kscrogi{at}lumc.edu

This article has been cited by other articles:

				R. Tiniakov and K. E. Scrogin The spleen is required for 5-HT1A receptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1392 - R1401. [Abstract] [Full Text] [PDF]

				R. Tiniakov, P. Osei-Owusu, and K. E. Scrogin The 5-Hydroxytryptamine1A Receptor Agonist, (+)-8-Hydroxy-2-(di-n-propylamino)-tetralin, Increases Cardiac Output and Renal Perfusion in Rats Subjected to Hypovolemic Shock J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 811 - 818. [Abstract] [Full Text] [PDF]