Prevention of diminished parasympathetic control of the heart in experimental heart failure.
Decreased synaptic transmission in parasympathetic ganglia contributes to abnormal parasympathetic function in heart failure (HF). Because nicotinic ACh receptors (nAChR) mediate synaptic transmission at the ganglion and upregulate in response to chronic exposure to agonist in vitro, we tested the hypothesis that repeated exposures of ganglionic neurons to a nAChR agonist can prevent a loss of parasympathetic control in HF. Two sets of experiments were performed. In set 1, unpaced control dogs and dogs undergoing pacing-induced HF were treated with a repeated intravenous nicotinic agonist during the development of HF. Under conditions of sympathetic blockade, R-R responses to a bolus injection of 200 microg 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP; nicotinic agonist) were found to be increased five times over the untreated group after 6 wk. In experimental set 2, dogs treated with weekly DMPP injections and in HF were anesthetized and underwent electrical stimulation of the right vagus nerve, which showed sinus cycle length responses >10 times that of controls (P < 0.05). Complete ganglionic blockade with hexamethonium abolished all responses, confirming that synaptic transmission was mediated entirely by nAChRs in both controls and HF. Despite decreased ganglionic function leading to reduced parasympathetic control of the heart in HF, repeated exposure with a nicotinic agonist during the development of HF results in not only preserved but also supranormal effects of parasympathetic stimulation on the sinus node.
Bibevski
Steve
S
Departmrnt of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA. steven.bibevski@case.edu
Dunlap
Mark E
ME
D000818:Animals; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004285:Dogs; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D018722:Nicotinic Agonists / Q000494:pharmacology; D010138:Pacemaker, Artificial; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D011978:Receptors, Nicotinic / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide