The role of reflexes in modifying the response to bethanechol chloride: A basis for selectivity of action on the bladder

When bethanechol is administered subcutaneously it induces a reflex-dependent sustained bladder contraction, and causes significant salivation but has little effect on blood pressure or heart rate. This relative selectivity of action is important for the clinical utility of the drug. We tested the hypothesis that the absence of cardiovascular effects is due to reflex compensation by assessing bethanechol's actions after blocking these reflexes. In chloralose-anesthetized cats the bladder was cannulated for pressure recording. Bethanechol (0.055–0.20 mg/kg SC) caused a sustained bladder contraction with no significant change in heart rate. During hexamethonium infusion (2 mg/min IV) SC bethanechol caused a fall in heart rate with no bladder contraction. Thus, strong cardiac compensatory reflexes normally prevent bethanechol-induced bradycardia. The time course of bradycardia and bladder contraction in the same bethanechol injection were compared during blockade with the β₁-antagonist metoprolol (0.4 mg/kg IV). The nadir of the bradycardia did not coincide with the sustained bladder contraction. Furthermore, the time to peak bladder effect diminished with SC dose while the time to nadir of bradycardia did not. If the time course of the bradycardia reflects plasma bethanechol concentration, then triggering of the bladder reflex cannot be related directly to this level. The difference in latency may be related to distribution barriers or to response time differences.