In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 14 ( 2004-04-06), p. 4948-4953
Abstract:
The clinical effects of treatment withn β-adrenoceptor (β-AR) agonists and antagonists in heart failure vary with duration of therapy, as do the effects of β-AR agonists in asthma. Therefore, we hypothesized that chronic effects of “β-blockers” in asthma may differ from those observed acutely. We tested this hypothesis in an antigen (ovalbumin)-driven murine model of asthma. Airway resistance responses ( R aw ) to the muscarinic agonist methacholine were measured by using the forced oscillation technique. In comparison with nontreated asthmatic mice, we observed that: ( i ) The β-AR antagonists nadolol or carvedilol, given as a single i.v. injection (acute treatment) 15 min before methacholine, increased methacholine-elicited peak R aw values by 33.7% and 67.7% ( P 〈 0.05), respectively; when either drug was administered for 28 days (chronic treatment), the peak R aw values were decreased by 43% ( P 〈 0.05) and 22.9% ( P 〈 0.05), respectively. ( ii ) Chronic treatment with nadolol or carvedilol significantly increased β-AR densities in lung membranes by 719% and 828%, respectively. ( iii ) Alprenolol, a β-blocker with partial agonist properties at β-ARs, behaved as a β-AR agonist, and acutely reduced peak R aw value by 75.7% ( P 〈 0.05); chronically, it did not alter R aw .( iv ) Salbutamol, a β-AR partial agonist, acutely decreased peak R aw by 41.1%; chronically, it did not alter R aw . ( v ) None of the β-blockers produced significant changes in eosinophil number recovered in bronchoalveolar lavage. These results suggest that β-AR agonists and β-blockers with inverse agonist properties may exert reciprocating effects on cellular signaling dependent on duration of administration.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0400452101
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2004
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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