Diabetes attenuates the minimum anaesthetic concentration (MAC) and MAC-blocking adrenergic response reducing actions of clonidine in rats

• Published in: Acta anaesthesiologica Scandinavica 2001-11, Vol.45 (10), p.1230-1234
• Main Authors: Kita, T., Kagawa, K., Mammoto, T., Takada, K., Hayashi, Y., Mashimo, T., Kishi, Y.
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Anesthesia, Inhalation; Anesthetics, Inhalation - pharmacokinetics; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; clonidine; Clonidine - pharmacology; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; Halothane - pharmacokinetics; Hemodynamics - drug effects; Insulin - therapeutic use; MAC-BAR; Male; Medical sciences; minimum anesthetic concentration (MAC); Neuropharmacology; Pain Threshold - drug effects; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; α2 adrenoceptor
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1034/j.1399-6576.2001.451010.x

Background: It is well known that clonidine, an α2 agonist, reduces anaesthetic requirement and attenuates haemodynamic responses against noxious stimuli. However, the diabetic state is known to affect several functions of α2 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 · 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 μg · kg−1, IV) was completely abolished and MAC‐BAR reducing action of clonidine was partially reduced (30 but not 100 μg · kg−1, IV). Insulin treatment preserved these actions of clonidine. Conclusion: It is suggested that the diabetic state attenuates the beneficial actions of clonidine and that insulin treatment of diabetes preserves these actions of clonidine.