Received for publication June 5, 2006.
Revised July 31, 2006.
Accepted for publication August 1, 2006.

The Serotonin 5-HT1A-receptor agonist, 8-OH-DPAT, stimulates sympathetic-dependent increases in venous tone during hypovolemic shock

Abstract

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 utilize agents that also promote venoconstriction to augment perfusion pressure through increased venous return. Recent studies indicate that 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-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 vs. saline) and mean circulatory filling pressure (+4.2 ± 0.7 mm Hg, P<0.01 vs. 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.

Key words: blood pressure, hemorrhage, serotonin, sympathetic, vasoconstriction, veins

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