Impaired cardiac and sympathetic autonomic control in rats differing in acetylcholine receptor sensitivity

1 Hypertension and Stroke Research Laboratories, Department of Physiology, University of Sydney and Department of Neurosurgery, Royal North Shore Hospital, St. Leonards New South Wales, Australia; and 2 Skipper Bowles Center for Alcohol Studies, Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina Submitted 29 April 2005 ; accepted in final form 6 June 2005 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 with Sprague-Dawley rats (SD), confirmed by using hypothermic responses evoked by the muscarinic agonist oxotremorine (0.2 mg/kg ip) ( n 9 rats/group). Arterial pressure, ECG, and splanchnic sympathetic (SNA) and phrenic (PNA) nerve activities were acquired under anesthesia (urethane 1.3 g/kg ip). HRV was assessed in time and frequency domains from short-term R-R interval data, and spontaneous heart rate BRS was obtained by using a sequence method at rest and after administration of atropine methylnitrate (mATR, 2 mg/kg iv). Heart rate and SNA baroreflex gains were assessed by using conventional pharmacological methods. FRL and FSL were normotensive but displayed elevated heart rates, reduced HRV and HF power, and spontaneous BRS compared with 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 with 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. heart rate variability; baroreflex sensitivity; Flinders Sensitive line; Flinders Resistant line Address for reprint requests and other correspondence: A. K. Goodchild, Hypertension and Stroke Research Laboratories, Ground Floor Block 3, Dept. of Neurosurgery, Royal North Shore Hospital, St. Leonards, NSW Australia 2065 (e-mail: anng{at}physiol.usyd.edu.au )