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Acid‐Sensing Ion Channel‐1a Differentially Contributes to Blood Pressure and Heart Rate Responses to Hypoxia and Hypercapnia
Author(s) -
Sabharwal Rasna,
Wemmie John A,
Abboud Francois M,
Chapleau Mark W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.739.5
Subject(s) - hypercapnia , bradycardia , hypoxia (environmental) , heart rate , endocrinology , medicine , blood pressure , chemistry , anesthesia , acidosis , oxygen , organic chemistry
Hypoxia and hypercapnia influence blood pressure (BP) and heart rate (HR) through multiple mechanisms including chemoreflex activation, central neural actions, and peripheral effects on heart and vasculature. A cid‐ S ensing I on C hannel‐1 (ASIC1) is expressed in tissues implicated in hypoxia‐ and/or acid‐sensing including carotid body glomus cells, and sensory and central neurons. We hypothesized that ASIC1a contributes to BP and HR responses to hypoxia and hypercapnia. BP and HR were recorded by telemetry in ASIC1a−/− (n=5) and wild‐type (WT) mice (n=9) before and during 10‐min exposures to hypoxia (10% O 2 ) and hypercapnia (5 and 10% CO 2 ). Mean BP and HR during normoxia did not differ in ASIC1a−/− and WT mice (127±3 vs. 117±4 mmHg, 707±18 vs. 712±34 bpm). HR increased transiently during hypoxia in WT and ASIC1a−/− mice (+35±14 and +48±11 bpm), and then decreased over time as did BP. The hypoxia‐induced bradycardia and hypotension were significantly enhanced in ASIC1a−/− mice vs. WT (see Table, *P<0.05). Sustained hypercapnia also decreased HR and BP in WT mice. Notably, CO 2 ‐hypotension did not occur in ASIC1a−/− mice despite an enhanced bradycardia (Table). We conclude that ASIC1a mediates hypercapnia‐induced hypotension but opposes the CO 2 ‐bradycardia. In contrast, ASIC1a‐dependent mechanisms oppose hypoxia‐induced hypotension and bradycardia. The results suggest that ASIC1a may contribute to autonomic responses and to the direct cardiac and vascular effects of hypoxia and hypercapnia in a differential manner. (AHA 0725771Z, HL14388)