Ventral medulla sites of muscarinic receptor subtypes involved in cardiorespiratory control

Bilateral 10-nl injections of the muscarinic (M1) receptor antagonist pirenzepine (PZ) and the M3-antagonist 4-diphenylacetoxy-N-methylpiperidine (DAMP) just below the surface of the rostral ventrolateral medulla (VLM) in anesthetized, paralyzed, vagotomized, glomectomized, servo-ventilated cats decreased base-line phrenic activity and CO2 sensitivity but not blood pressure. Unilateral 10-nl injections of PZ, DAMP, or the M2-antagonist AFDX-116 resulted in the following. AFDX-116 greater than PZ greater than DAMP decreased blood pressure. DAMP greater than PZ greater than AFDX-116 decreased base-line phrenic activity and the CO2 response slope. Many injections had no effect, and some affected only one variable. The injection sites were within 700 microns of the VLM surface extending from the caudal aspect of the superior olive through a region ventromedial to the facial nucleus to the rostral aspect of the inferior olive. In a small number of experiments the response to carotid sinus nerve stimulation was affected by some injections of each antagonist. In the rostral VLM cardiovascular regulation involves M2-receptors, whereas respiratory regulation involves predominantly the M3-subtype. Neurons with these receptors appear to be closely intermingled.