Spinal alpha(2)-adrenoceptors are involved in the MACbar-sparing effect of systemic clonidine in rats.
We evaluated the central or spinal mechanism involved in the MACbar-sparing effect of systemic clonidine by using intrathecal alpha-adrenergic antagonist administration. The minimum alveolar concentration of sevoflurane that blocks cardiovascular response to a noxious stimulus (MACbar(sevo)) was determined in rats after treatment with IV saline, IV clonidine 10 micro g/kg, intrathecal (IT) or IV phentolamine 50 micro g, IT or IV yohimbine 200 micro g, IT or IV prazosin 30 micro g, or the combination of IV clonidine and the different IT or IV alpha-adrenergic antagonists. In the studied model, the MACbar(sevo) 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 MACbar(sevo) 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 MACbar(sevo) (2.78 +/- 1) when compared with controls (P < 0.05). IT prazosin alone significantly reduced the MACbar(sevo) (0.35 +/- 0.3; P< 0.05) and suppressed any hemodynamic reaction when combined with IV clonidine. The IV administration of the different alpha-adrenergic antagonists had no significant effect on the MACbar(sevo) 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 alpha-antagonists displayed different effects in rats under sevoflurane anesthesia than those reported in awake animals.


CONCLUSIONS
Using intrathecal alpha-adrenergic antagonist administration, we demonstrated that a spinal mechanism is involved in the MACbar-sparing effect of systemic clonidine in rats.
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D008738:Methyl Ethers; D010646:Phentolamine / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D000077149:Sevoflurane; D013116:Spinal Cord / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D000077149:Sevoflurane; D003000:Clonidine; D010646:Phentolamine