Altered baroreflex responses in alpha7 deficient mice.
The autonomic nervous system controls and coordinates several cardiovascular functions, including heart rate, arterial pressure, blood flow and vasomotor tone. Neuronal nicotinic acetylcholine receptors (nAChRs) are the interface between the nervous system and the cardiovascular system, but it is not known which nAChR subtypes regulate autonomic function in vivo. Nicotinic AChRs containing the alpha7 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 via postsynaptic mechanisms. To investigate the role of the alpha7 nAChR subunit in cardiac autonomic function, we measured baroreflex-mediated responses in alpha7 null mice. Here we show that the alpha7 null mice have impaired sympathetic responses to vasodilatation, as sodium nitroprusside infusion triggered a 48% heart rate increase in wild type mice but only a 21% increase in the alpha7 nulls (P < 0.001). The mutant mice developed supersensitivity to adrenergic agonists, although norepinephrine release from sympathetic nerve terminals could be elicited through mechanisms alternative to nAChR stimulation. Baroreflex-mediated parasympathetic responses were normal in alpha7 null mice. The decreased baroreflex-mediated tachycardia in alpha7 mutant mice indicates that alpha7-containing nAChRs participate in the autonomic reflex that maintains blood pressure homeostasis. The alpha7 mutant mice may serve as a model of baroreflex impairment arising from autonomic dysfunction.
Franceschini
D
D
Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Orr-Urtreger
A
A
Yu
W
W
Mackey
L Y
LY
Bond
R A
RA
Armstrong
D
D
Patrick
J W
JW
Beaudet
A L
AL
De Biasi
M
M
D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D006339:Heart Rate / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011311:Pressoreceptors / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor