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Effects of long term losartan treatment on D2 receptor modulation of breathing in the dystrophic hamster in air and following intermittent hypoxic bouts
Author(s) -
Schlenker Evelyn Heymann,
Richards Abby
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.1233.2
Subject(s) - losartan , endocrinology , ventilation (architecture) , medicine , chemistry , hamster , receptor , angiotensin ii , mechanical engineering , engineering
Angiotensin II (A) acting through A1 receptors and hypoxia release dopamine in several brain regions and the carotid body. Blockade of dopaminergic receptors (D2) modulates ventilation in the hamster. We tested the hypothesis that two months of losartan (L, an A1 receptor blocker, 50 mg/kg) treatment would affect D2‐modulated control of breathing during exposure to air and five minutes each of three bouts of 10% O2 interspersed with air (IH) differently compared to tap water‐treated dystrophic (D) hamsters. Ventilation was evaluated in conscious control (C), CL, D and DL hamsters injected with vehicle or domperidone, a D2 receptor antagonist (Dom) that does not cross the blood‐brain barrier. During baseline air exposure, frequency (f) was higher in the C versus the D groups. Dom normalized f and increased tidal volume in the DL group relative to CL. Dom doubled minute ventilation (MV) in DL relative to the D group, but did not affect C or CL groups. To evaluate the effects of IH, the ratio of MV during the third bout of IH to baseline (H/B) was determined. In DL, Dom relative to vehicle had no effect on MV H/B but in D hamsters Dom increased MV H/B (1.2 ± 0.12 vs. 1.8 ± 0.14, P=0.02). Losartan had no effect on MV H/B in the control groups. These results suggest that in dystrophic hamsters breathing air or hypoxia losartan alters D2‐modulated control of breathing by acting on the carotid body.