Back to Search
Start Over
Diaphragm weakness in pulmonary arterial hypertension: role of sarcomeric dysfunction.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2012 Dec 15; Vol. 303 (12), pp. L1070-8. Date of Electronic Publication: 2012 Sep 07. - Publication Year :
- 2012
-
Abstract
- We previously demonstrated that diaphragm muscle weakness is present in experimental pulmonary arterial hypertension (PH). However, the nature of this diaphragm weakness is still unknown. Therefore, the aim of this study was to investigate whether changes at the sarcomeric level contribute to diaphragm weakness in PH. For this purpose, in control rats and rats with monocrotaline-induced PH, contractile performance and myosin heavy chain content of demembranated single diaphragm fibers were determined. We observed a reduced maximal tension of 20% (P < 0.05), whereas tension cost was preserved in type 2X and 2B diaphragm fibers in PH compared with control. The reduced maximal tension was associated with a reduction of force generated per half-sarcomeric myosin heavy chain content. Additionally, reduced Ca(2+) sensitivity of force generation was found in type 2X fibers compared with control, which could exacerbate diaphragm muscle weakness at submaximal activation. No changes in maximal tension and Ca(2+) sensitivity of force generation were observed in fibers from the nonrespiratory extensor digitorum longus muscle. Together, these findings indicate that diaphragm weakness in PH is at least partly caused by sarcomeric dysfunction, which appears to be specific for the diaphragm.
- Subjects :
- Animals
Calcium pharmacology
Diaphragm drug effects
Familial Primary Pulmonary Hypertension
Hypertension, Pulmonary chemically induced
Male
Monocrotaline toxicity
Muscle Contraction drug effects
Muscle Contraction physiology
Muscle Fibers, Skeletal drug effects
Muscle Fibers, Skeletal physiology
Muscle Weakness chemically induced
Myosin Heavy Chains analysis
Myosin Heavy Chains physiology
Rats
Rats, Wistar
Sarcomeres drug effects
Diaphragm physiopathology
Hypertension, Pulmonary physiopathology
Muscle Weakness physiopathology
Sarcomeres physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1504
- Volume :
- 303
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 22962018
- Full Text :
- https://doi.org/10.1152/ajplung.00135.2012