Abstract
The aim of this study was to evaluate the potential mechanisms underlying the improved contractility of the diaphragm (Dia) in adult intact male hamsters after nandrolone (Nan) administration, given subcutaneously over 4 wk via a controlled-release capsule (initial dose: 4.5 mg · kg-1 · day-1; with weight gain, final dose: 2.7 mg · kg-1 · day-1). Control (Ctl) animals received blank capsules. Isometric contractile properties of the Dia were determined in vitro after 4 wk. The maximum velocity of unloaded shortening (V0) was determined in vitro by means of the slack test. Dia fibers were classified histochemically on the basis of myofibrillar ATPase staining and fiber cross-sectional area (CSA), and the relative interstitial space was quantitated. Ca2+-activated myosin ATPase activity was determined by quantitative histochemistry in individual diaphragm fibers. Myosin heavy chain (MHC) isoforms were identified electrophoretically, and their proportions were determined by using scanning densitometry. Peak twitch and tetanic forces, as well as V0, were significantly greater in Nan animals compared with Ctl. The proportion of type IIa Dia fibers was significantly increased in Nan animals. Nan increased the CSA of all fiber types (26-47%), whereas the relative interstitial space decreased. The relative contribution of fiber types to total costal Dia area was preserved between the groups. Proportions of MHC isoforms were similar between the groups. There was a tendency for increased expression of MHC(2B) with Nan. Ca2+-activated myosin ATPase activity was increased 35-39% in all fiber types in Nan animals. We conclude that, after Nan administration, the increase in Dia specific force results from the relatively greater Dia CSA occupied by hypertrophied muscle fibers, whereas the increased ATPase activity promotes a higher rate of crossbridge turnover and thus increased V0. We speculate that Nan in supraphysiological doses have the potential to offset or ameliorate conditions associated with enhanced proteolysis and disordered protein turnover.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 985-992 |
| Number of pages | 8 |
| Journal | Journal of Applied Physiology |
| Volume | 86 |
| Issue number | 3 |
| State | Published - Mar 1999 |
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Keywords
- Anabolic-androgenic steroids
- Calcium activated- myosin adenosinetriphosphatase
- Muscle fiber size
- Muscle specific force
- Muscle velocity of shortening
- Myosin heavy chains
- Respiratory muscles
ASJC Scopus subject areas
- Endocrinology
- Physiology
- Orthopedics and Sports Medicine
- Physical Therapy, Sports Therapy and Rehabilitation
Cite this
Alterations in diaphragm contractility after nandrolone administration : An analysis of potential mechanisms. / Lewis, Michael I.; Fournier, Mario; Yeh, Amelia Y.; Micevych, Paul E.; Sieck, Gary C.
In: Journal of Applied Physiology, Vol. 86, No. 3, 03.1999, p. 985-992.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alterations in diaphragm contractility after nandrolone administration
T2 - An analysis of potential mechanisms
AU - Lewis, Michael I.
AU - Fournier, Mario
AU - Yeh, Amelia Y.
AU - Micevych, Paul E.
AU - Sieck, Gary C
PY - 1999/3
Y1 - 1999/3
N2 - The aim of this study was to evaluate the potential mechanisms underlying the improved contractility of the diaphragm (Dia) in adult intact male hamsters after nandrolone (Nan) administration, given subcutaneously over 4 wk via a controlled-release capsule (initial dose: 4.5 mg · kg-1 · day-1; with weight gain, final dose: 2.7 mg · kg-1 · day-1). Control (Ctl) animals received blank capsules. Isometric contractile properties of the Dia were determined in vitro after 4 wk. The maximum velocity of unloaded shortening (V0) was determined in vitro by means of the slack test. Dia fibers were classified histochemically on the basis of myofibrillar ATPase staining and fiber cross-sectional area (CSA), and the relative interstitial space was quantitated. Ca2+-activated myosin ATPase activity was determined by quantitative histochemistry in individual diaphragm fibers. Myosin heavy chain (MHC) isoforms were identified electrophoretically, and their proportions were determined by using scanning densitometry. Peak twitch and tetanic forces, as well as V0, were significantly greater in Nan animals compared with Ctl. The proportion of type IIa Dia fibers was significantly increased in Nan animals. Nan increased the CSA of all fiber types (26-47%), whereas the relative interstitial space decreased. The relative contribution of fiber types to total costal Dia area was preserved between the groups. Proportions of MHC isoforms were similar between the groups. There was a tendency for increased expression of MHC(2B) with Nan. Ca2+-activated myosin ATPase activity was increased 35-39% in all fiber types in Nan animals. We conclude that, after Nan administration, the increase in Dia specific force results from the relatively greater Dia CSA occupied by hypertrophied muscle fibers, whereas the increased ATPase activity promotes a higher rate of crossbridge turnover and thus increased V0. We speculate that Nan in supraphysiological doses have the potential to offset or ameliorate conditions associated with enhanced proteolysis and disordered protein turnover.
AB - The aim of this study was to evaluate the potential mechanisms underlying the improved contractility of the diaphragm (Dia) in adult intact male hamsters after nandrolone (Nan) administration, given subcutaneously over 4 wk via a controlled-release capsule (initial dose: 4.5 mg · kg-1 · day-1; with weight gain, final dose: 2.7 mg · kg-1 · day-1). Control (Ctl) animals received blank capsules. Isometric contractile properties of the Dia were determined in vitro after 4 wk. The maximum velocity of unloaded shortening (V0) was determined in vitro by means of the slack test. Dia fibers were classified histochemically on the basis of myofibrillar ATPase staining and fiber cross-sectional area (CSA), and the relative interstitial space was quantitated. Ca2+-activated myosin ATPase activity was determined by quantitative histochemistry in individual diaphragm fibers. Myosin heavy chain (MHC) isoforms were identified electrophoretically, and their proportions were determined by using scanning densitometry. Peak twitch and tetanic forces, as well as V0, were significantly greater in Nan animals compared with Ctl. The proportion of type IIa Dia fibers was significantly increased in Nan animals. Nan increased the CSA of all fiber types (26-47%), whereas the relative interstitial space decreased. The relative contribution of fiber types to total costal Dia area was preserved between the groups. Proportions of MHC isoforms were similar between the groups. There was a tendency for increased expression of MHC(2B) with Nan. Ca2+-activated myosin ATPase activity was increased 35-39% in all fiber types in Nan animals. We conclude that, after Nan administration, the increase in Dia specific force results from the relatively greater Dia CSA occupied by hypertrophied muscle fibers, whereas the increased ATPase activity promotes a higher rate of crossbridge turnover and thus increased V0. We speculate that Nan in supraphysiological doses have the potential to offset or ameliorate conditions associated with enhanced proteolysis and disordered protein turnover.
KW - Anabolic-androgenic steroids
KW - Calcium activated- myosin adenosinetriphosphatase
KW - Muscle fiber size
KW - Muscle specific force
KW - Muscle velocity of shortening
KW - Myosin heavy chains
KW - Respiratory muscles
UR - http://www.scopus.com/inward/record.url?scp=0032983064&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032983064&partnerID=8YFLogxK
M3 - Article
C2 - 10066714
AN - SCOPUS:0032983064
VL - 86
SP - 985
EP - 992
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 8750-7587
IS - 3
ER -