Intrathecal cholinergic agonists lessen bupivacaine spinal-block-induced hypotension in rats

Hypotension is an important side effect of spinal anesthesia. Intrathecal (IT) cholinergic agonists, including neostigmine (NEO), increase arterial blood pressure by stimulating spinal sympathetic neurons. Therefore, we tested the ability of IT cholinergic agonists to prevent the hypotensive effect of IT bupivacaine (BUP) (430 nmol) in rats instrumented with IT and arterial catheters. The mean arterial pressure (MAP) decreased 35 +/- 4 mm Hg (n = 10) after IT-BUP alone. In contrast, MAP did not significantly change after IT-BUP + IT-NEO (12.5 and 25 nmol; n = 5 for each dose). Intramuscular (IM) NEO was not effective, and MAP decreased 38 +/- 4 mm Hg after IT-BUP + IM-NEO (25 nmol; n = 5). Three additional cholinesterase inhibitors, physostigmine, edrophonium, and ambenonium, as well as the direct-acting cholinergic agonists carbachol, oxotremorine, and arecoline, each lessened the hypotension seen after IT-BUP. Furthermore, the nonselective muscarinic antagonist, atropine, as well as the M2 receptor selective antagonist, methoctramine, prevented the vasopressor effect of IT-NEO in our model. Finally, the nicotinic antagonist, mecamylamine, and the M1 selective antagonist, pirenzepine, did not affect the pressor effects of NEO in our model. In conclusion, IT cholinergic agonists lessen BUP spinal-block-induced hypotension in rats by a muscarinic dependent pathway.