Acetylcholine receptors (AChR) are important in premotor and efferent control of autonomic function; however, the extent to which cardiovascular function is affected by genetic variations in AChR sensitivity is unknown. We assessed heart rate variability (HRV) and baroreflex sensitivity (BRS) in rats bred for resistance (FRL) or sensitivity (FSL) to cholinergic agents compared to Sprague Dawley rats (SD), confirmed using hypothermic responses evoked by the muscarinic agonist oxotremorine (0.2 mg/kg i.p.) (n 9 / group). Arterial pressure, ECG and splanchnic sympathetic (SNA) and phrenic (PNA) nerve activities were acquired under anaesthesia (urethane 1.3 g/kg i.p.). HRV was assessed in time and frequency domains from short term R-R interval data and spontaneous heart rate BRS was obtained using a sequence method at rest and after methylatropine (mATR, 2 mg/kg i.v.). Heart rate and SNA baroreflex gains were assessed using conventional pharmacological methods. FRL and FSL were normotensive but displayed elevated heart rates, reduced HRV and HF power and spontaneous BRS compared to SD. mATR had no effect on these parameters in FRL or FSL, indicating reduced cardiovagal tone. FSL exhibited reduced PNA frequency, longer baroreflex latency and reduced baroreflex gain of heart rate and SNA compared to FRL and SD, indicating in FSL dual impairment of cardiac and circulatory baroreflexes. These findings show that AChR resistance results in reduced cardiac muscarinic receptor function leading to cardiovagal insufficiency. In contrast, AChR sensitivity results in autonomic and respiratory abnormalities arising from alterations in central muscarinic and or other neurotransmitter receptors.