Interactions between the serotonergic and histaminergic systems in the central cardiovascular regulation in haemorrhage-shocked rats: involvement of 5-HT(1A) receptors.
Department of Basic Medical Sciences, Medical University of Silesia, Piekarska 18, 41-902, Bytom, Poland.Agents and Actions (Impact Factor: 1.59). 05/2009; 58 Suppl 1:38-40. DOI:10.1007/s00011-009-0658-6
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ABSTRACT: The 5-hydroxytryptamine(1A) receptor agonist, (+)-8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), raises blood pressure (BP) and venous tone in rats subjected to hemorrhagic shock. Here, BP, ascending aortic blood flow [i.e., estimate of cardiac output (CO)] and venous blood gases were measured to determine the hemodynamic effects of 8-OH-DPAT (30 nmol/kg i.v., n = 10), saline (n = 10), or an equipressor infusion of epinephrine (n = 10) in unanesthetized rats subjected to hemorrhagic shock (25 min of hypotensive hemorrhage, approximately 50 mm Hg). Renal and iliac blood flow were measured in separate groups of similarly hemorrhaged rats given the same dose of 8-OH-DPAT (n = 7) or saline (n = 6). Compared with saline treatment, 8-OH-DPAT produced a sustained rise in BP (+32 +/- 4 versus +9 +/- 2 mm Hg, 15 min after injection, P < 0.01) and CO (+27 +/- 5 versus +4 +/- 6 ml/min/kg, P < 0.01) but did not affect total peripheral resistance (TPR). Infusion of epinephrine reduced CO (-12 +/- 6 ml/min/kg, P < 0.01) and dramatically increased TPR [+0.37 +/- 0.11 versus +0.05 +/- 0.05 log (mm Hg/ml/min/kg), P < 0.01]. 8-OH-DPAT increased renal conductance (+7 +/- 1 versus +4 +/- 1 microl/min/mm Hg, P < 0.01) but did not significantly affect iliac conductance. 8-OH-DPAT attenuated further development of acidosis compared with either saline or epinephrine (-5.6 +/- 1.6 versus -13.0 +/- 2.0 versus -11.3 +/- 2.6 mmol/liter base excess 45 min after start of hemorrhage, both P < 0.01 versus 8-OH-DPAT). These data demonstrate that 8-OH-DPAT improves hemodynamics during circulatory shock, in part, through renal vasodilation and mobilizing of blood stores.Journal of Pharmacology and Experimental Therapeutics 03/2007; 320(2):811-8. · 3.89 Impact Factor
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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 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 alpha(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 alpha(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, alpha(1)-, or peripheral alpha(2)-adrenergic receptor blockade prevented the rise in MCFP observed with 8-OH-DPAT, but only alpha(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 alpha(1)-adrenergic receptors. The sympathoexcitatory effect of 8-OH-DPAT contributes to elevated venous tone through concurrent activation of both alpha(1)- and alpha(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.Journal of Pharmacology and Experimental Therapeutics 11/2006; 319(2):776-82. · 3.89 Impact Factor
- Inflammation Research 05/2007; 56 Suppl 1:S27-8. · 1.96 Impact Factor
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