Submitted on December 31, 2008
Revised on February 9, 2009
Accepted on February 23, 2009
The spleen is required for 5-HT1A receptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat
Ruslan Tiniakov1 and Karie E. Scrogin1*
1 Loyola University Chicago, Stritch School of Medicine
* To whom correspondence should be addressed. E-mail: kscrogi{at}lumc.edu.
The 5-HT1A-receptor agonist, 8-OH-DPAT, increases whole body venous tone (mean circulatory filling pressure; MCFP), and attenuates metabolic acidosis in a rat model of unresuscitated hemorrhagic shock. To determine if improved acid-base balance was associated with sympathetic activation and venous constriction, MCFP, sympathetic activity (SA) and blood gases were compared in hemorrhaged rats following administration of 8-OH-DPAT, the arterial vasoconstrictor arginine vasopressin (AVP), or saline. To further determine if protection of acid-base balance was dependent on splenic contraction and blood mobilization, central venous pressure (CVP), MCFP, and blood gases were determined during hemorrhage and subsequent 8-OH-DPAT-administration in rats subjected to real or sham-splenectomy. Subjects were hemorrhaged to an arterial pressure of 50 mmHg for 25 min and subsequently treated with 8-OH-DPAT (30 nmol/kg, iv), AVP titrated to match the pressor effect of 8-OH-DPAT (~2 ng/min, iv), or infusion of normal saline. 8-OH-DPAT increased MAP, CVP, MCFP, SA, and decreased lactate accumulation. Arginine vasopressin did not affect CVP or SA, but raised MCFP slightly to a level intermediate between 8-OH-DPAT or saline-treated rats. Infusion of AVP also produced a modest protection against metabolic acidosis. Splenectomy prevented the rise in CVP, MCFP and protection against metabolic acidosis produced by 8-OH-DPAT, but had no effect on the immediate pressor response to the drug. Together, the data indicate that 8-OH-DPAT produces a pattern of cardiovascular responses consistent with a sympathetic-mediated venoconstriction that is, in part, responsible for the drug's beneficial effect on acid-base balance. Moreover, blood mobilization stimulated by the spleen is required for the beneficial effects of 8-OH-DPAT.
