(The FASEB Journal. 2008;22:953.11)
© 2008 FASEB
(The FASEB Journal. 2008;22:953.11.)
© 2008 FASEB
Contrasting Autonomic and Cardiovascular Phenotypes in ASIC1a and ASIC2 deficient mice
Rasna Sabharwal1,
John A Wemmie2,4,
Francois M Abboud1,3 and
Mark W Chapleau1,4
1 Internal Medicine
2 Psychiatry
3 Molecular Physiology & Biophysics, University of Iowa, Iowa City, IA
4 Vet Aff Med Ctr, Iowa City, IA
ABSTRACT
Members of the acid-sensing ion channel (ASIC) family are differentially expressed in subpopulations of sensory and central neurons and have been implicated in a variety of neuronal functions. We recently demonstrated that mice deficient in ASIC2, a subunit implicated in mechanotransduction, exhibit baroreflex and autonomic dysfunction, and hypertension (FASEB J 20:2006). The goals of the present study were to characterize autonomic and cardiovascular phenotypes in conscious ASIC1a–/– mice and compare the results to those obtained in ASIC2–/– mice. Arterial blood pressure (BP), heart rate (HR), and locomotor activity were measured by radio-telemetry (DSI) in the mouse home cage. Mean BP and HR (24 hr avg.), cardiac sympathetic tone (HR response to propranolol), and sympathetic vasomotor tone (BP response to ganglionic blocker chlorisondamine) were all significantly higher in ASIC2–/– (n=5–7), but not different in ASIC1a–/– (n=7) vs. wild-type (WT, n=7) mice (Table, *P<0.05).
In contrast to the cardiovascular and autonomic phenotypes, locomotor activity was decreased in both ASIC1a–/– and ASIC2–/– mice compared with WT. We conclude: 1) ASIC1a does not contribute to baseline BP, HR, or sympathetic tone under resting conditions in conscious mice, 2) ASIC2 exerts a powerful restraining influence on sympathetic activity and BP, and 3) the ASIC2–/– mouse is a model of chronic neurogenic hypertension. (AHA 0725771Z, HL14388)
