Inhibition of GABAA receptors in the nucleus tractus solitarius induced cardiovascular depression during isoflurane inhalation anesthesia

Objective: Isoflurane is widely used for inhaled general anesthesia. However, the mechanisms of isoflurane-induced cardiovascular depression are not fully understood. The effect of isoflurane on GABAA receptor expression in the NTS may underlie cardiovascular depression. Methods: The blood pressure (BP) and heart rates (HR) of conscious rats were confirmed initially using a CODA non-invasive blood pressure monitor system. Rats were anesthetized with inhaled isoflurane or an intraperitoneal injection of urethane, and BP and HR were measured. BP and HR changes evoked by microinjections of L-glutamate, GABAA receptor agonists or antagonists into the NTS were observed. GABAA receptor mRNA and protein expression level changes following agonist or antagonist administration were detected using real-time PCR and Western blot analyses. Results: The depressor response to L-glutamate microinjection into the NTS was significantly increased in the urethane-anesthetized group compared with isoflurane group. GABAA receptor agonist and antagonist microinjections into the NTS did not significantly change the BP and HR in the isoflurane group, but the increasing or decreasing amplitudes of BP and HR of urethane group were significantly higher than isoflurane group. GABAA receptor agonist and antagonist microinjections significantly altered GABAA receptor mRNA and protein expression levels in the urethane group. Conclusion: These findings suggest that the function of GABAA receptors in the NTS was inhibited by inhaled isoflurane, which induced cardiovascular depression.