Received for publication September 20, 2006.
Revised November 1, 2006.
Accepted for publication November 1, 2006.

The 5-HT_1A-receptor agonist, 8-OH-DPAT, increases cardiac output and renal perfusion in rats subject to hypovolemic shock

Abstract

The 5-HT_1A receptor agonist, 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, iv, n = 10), saline (n = 10) or an equipressor infusion of epinephrine (n = 10) in unanesthetized rats subject to hemorrhagic shock (25 min of hypotensive hemorrhage, ~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 to saline treatment, 8-OH-DPAT produced a sustained rise in BP (+32 ± 4 vs. +9 ± 2 mm Hg, 15 min after injection, P<0.01) and CO (+27 ± 5 vs. +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 vs. +0.05 ± 0.05 log[mm Hg/ml/min/kg], P<0.01). 8-OH-DPAT increased renal conductance (+7 ± 1 vs. +4 ± 1 µl/min/mmHg, P<0.01), but did not significantly affect iliac conductance. 8-OH-DPAT attenuated further development of acidosis compared to either saline or epinephrine (-5.6 ± 1.6 vs. -13.0 ± 2.0* vs. -11.3 ±2.6* mmol/L Base Excess 45 min after start of hemorrhage, *P<0.01 vs. 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.

Key words: blood flow, cardiac output, hemorrhage, iliac, renal, serotonin