Diabetes attenuates the minimum anaesthetic concentration (MAC) and MAC-blocking adrenergic response reducing actions of clonidine in rats.
BACKGROUND
It is well known that clonidine, an alpha2 agonist, reduces anaesthetic requirement and attenuates haemodynamic responses against noxious stimuli. However, the diabetic state is known to affect several functions of alpha2 adrenoceptors. We investigated the effects of streptozotocin (STZ)-induced diabetes mellitus (DM) on these beneficial actions of clonidine in halothane-anaesthetized rats.


METHODS
The rats were randomly assigned to one of three groups: diabetes (n=24, induced by 50 mg x kg(-1) IV STZ), diabetes treated with insulin (n=24), or control (n=24). We evaluated the effects of clonidine on minimum anaesthetic concentration (MAC) and minimum concentration of halothane needed to suppress cardiovascular responses evoked by a noxious stimulus (MAC-blocking adrenergic responses: MAC-BAR) in each group. MAC and MAC-BAR of halothane were determined by the tail clamp method. MAC-BAR was defined as the MAC which attenuated haemodynamic responses within 10% following the tail clamp.


RESULTS
The diabetic state decreased MAC of halothane by approximately 10%, while MAC-BAR of halothane had been little affected. In the diabetes group, MAC reducing action of clonidine (30 and 100 microg x kg(-1), IV) was completely abolished and MAC-BAR reducing action of clonidine was partially reduced (30 but not 100 microg x kg(-1), IV). Insulin treatment preserved these actions of clonidine.


CONCLUSIONS
It is suggested that the diabetic state attenuates the beneficial actions of clonidine and that insulin treatment of diabetes preserves these actions of clonidine.
Kita
T
T
Department of Anesthesiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari, Osaka, Japan. tkita@cvn.bai.ne.jp
Kagawa
K
K
Mammoto
T
T
Takada
K
K
Hayashi
Y
Y
Mashimo
T
T
Kishi
Y
Y
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D006221:Halothane / Q000493:pharmacokinetics; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D018685:Anesthetics, Inhalation; D007328:Insulin; D003000:Clonidine; D006221:Halothane