The spleen is required for 5-HT_1Areceptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat

Abstract

The 5-HT(1A) 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 whether 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 5-HT(1A) receptor agonist 8-OH-DPAT, the arterial vasoconstrictor arginine vasopressin (AVP), or saline. To further determine whether 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 were treated with 8-OH-DPAT (30 nmol/kg iv), AVP titrated to match the pressor effect of 8-OH-DPAT (approximately 2 ng/min iv), or infusion of normal saline. 8-OH-DPAT increased MAP, CVP, MCFP, and SA, and decreased lactate accumulation. AVP did not affect CVP or SA, but raised MCFP slightly to a level intermediate between 8-OH-DPAT- and 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.

Serotonin neurons of the caudal raphe nuclei contribute to sympathetic recovery following hypotensive hemorrhage

“…It is clear that changes in RSNA often do not track with changes in sympathetic drive to other vascular beds that are important in maintaining peripheral resistance (26). Nevertheless, we have found that changes in RSNA parallel those of splanchnic nerve activity during progressive blood loss and subsequent hemorrhagic shock (43). Thus the uncoupling of blood pressure recovery from RSNA recovery was surprising.…”

Vasopressin and Its Immune Effects in Septic Shock

“…Vasopressin also increases venous vascular tone so that mean systemic filling pressure is increased by vasopressin administration [41] . This effect should increase venous return.…”

Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock

“…However, there was no longer any group difference in MCFP 20 min after the start of hemorrhage. This was surprising given our evidence that this hemorrhage model demonstrates a significant and persistent secondary increase in sympathetic activity that tends to peak 25 min after the start of hemorrhage (30). We expected that the progressive rise in sympathetic activity would increase venoconstriction in intact animals, but not SD rats.…”

“…The 1/60 factor accounts for the difference in compliance between the arterial and venous vasculature in the rat. Measurements of VPP and FAP were taken once hemodynamic equilibrium was reached, usually, within 5 s of circulatory arrest, prior to activation of sympathetic reflexes (30). Total blood withdrawn was weighed to obtain a measure of total loss assuming a blood density of 1 g/ml.…”