Spinal α2-Adrenoceptors Are Involved in the MACbar-Sparing Effect of Systemic Clonidine In Rats

Abstract

We evaluated the central or spinal mechanism involved in the MACbar-sparing effect of systemic clonidine by using intrathecal α-adrenergic antagonist administration. The minimum alveolar concentration of sevoflurane that blocks cardiovascular response to a noxious stimulus (MACbarsevo) was determined in rats after treatment with IV saline, IV clonidine 10 μg/kg, intrathecal (IT) or IV phentolamine 50 μg, IT or IV yohimbine 200 μg, IT or IV prazosin 30 μg, or the combination of IV clonidine and the different IT or IV α-adrenergic antagonists. In the studied model, the MACbarsevo of saline-treated controls was 2.10 ± 0.8. After clonidine administration, it decreased to 1.07 ± 0.4. The IT administration of phentolamine and yohimbine did not modify the MACbarsevo of naïve rats, whereas in IV clonidine-treated animals, it totally suppressed the MAC-sparing effect of this drug (phentolamine) or even significantly increased (yohimbine) the MACbarsevo (2.78 ± 1) when compared with controls (P < 0.05). IT prazosin alone significantly reduced the MACbarsevo (0.35 ± 0.3;P < 0.05) and suppressed any hemodynamic reaction when combined with IV clonidine. The IV administration of the different α-adrenergic antagonists had no significant effect on the MACbarsevo of controls or IV clonidine-treated animals. These results argue for a spinal mechanism of action involved in the MACbar-sparing effect of systemic clonidine. Moreover, the spinally administered α-antagonists displayed different effects in rats under sevoflurane anesthesia than those reported in awake animals.