Role of the orexinergic system in acute haemorrhage in the rat

Orexins (OXs) stimulate sympathetic nerve activity to increase arterial pressure (AP) and heart rate (HR). We have previously reported that the OX1-receptor antagonist SB-334867 reversed the sympathomimetic actions of orexin A (OXA). In the present study we have investigated the role(s) of the orexinergic system in sympathetic activation during haemorrhage in rats. Sixteen Wistar rats, anaesthetised with pentobarbital, were assigned to 2 groups: saline i.p. (group S) and SB-334867 30 mg/kg i.p. (group SB) n = 8 each. Haemorrhagic shock was established by acute withdrawal of 10 ml/kg of blood via an arterial catheter three times with a 30 min interval between each withdrawal. Haemodynamics were assessed 30 min after 10, 20, and 30 ml/kg of blood withdrawal. In addition, plasma orexin A and catecholamine concentrations in the shed blood were determined. In both groups, mean AP (MAP) and HR decreased significantly. Plasma catecholamine concentrations significantly increased following blood withdrawal. The reduction in MAP/HR and elevation of catecholamine levels were dependent on the total amount of shed blood. There were no differences between the groups. Plasma OXA concentrations increased to a greater extent in group SB than group S in response to haemorrhage. There was a significant correlation between plasma catecholamines and %change in MAP (epinephrine: r = 0.553, p = 0.0001, norepinephrine: r = 0.374, p = 0.0087) and HR (epinephrine: r = 0.403, p = 0.005, norepinephrine: r = 0.436, p = 0.002). There was no correlation with plasma orexin A levels. These data suggest that despite a weak activation the orexinergic system is unlikely to make a major contribution to the response to haemorrhage.