Altered baroreflex responses in alpha 7 deficient mice

The autonomic nervous system controls and coordinates several cardiovascula r functions, including heart rate, arterial pressure, blood flow and vasomo tor tone. Neuronal nicotinic acetylcholine receptors (nAChRs) are the inter face between the nervous system and the cardiovascular system, but it is no t known which nAChR subtypes regulate autonomic function in vivo. Nicotinic AChRs containing the alpha 7 subunit are a candidate subtype in autonomic ganglia. Stimulation of these nAChRs can increase neurotransmitter release via presynaptic mechanisms, as well as mediate fast synaptic transmission v ia postsynaptic mechanisms. To investigate the role of the alpha 7 nAChR su bunit in cardiac autonomic function, we measured baroreflex-mediated respon ses in alpha 7 null mice. Here we show that the alpha 7 null mice have impa ired sympathetic responses to vasodilatation, as sodium nitroprusside infus ion triggered a 48% heart rate increase in wild type mice but only a 21% in crease in the alpha 7 nulls (P < 0.001). The mutant mice developed supersen sitivity to adrenergic agonists, although norepinephrine release from sympa thetic nerve terminals could be elicited through mechanisms alternative to nAChR stimulation. Baroreflex-mediated parasympathetic responses were norma l in alpha 7 null mice. The decreased baroreflex-mediated tachycardia in al pha 7 mutant mice indicates that alpha 7-containing nAChRs participate in t he autonomic reflex that maintains blood pressure homeostasis. The alpha 7 mutant mice may serve as a model of baroreflex impairment arising from auto nomic dysfunction. (C) 2000 Elsevier Science B.V. All rights reserved.