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 (Vo) 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 Vo, 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 MHC2B 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 cross-bridge turnover and thus increased Vo. We speculate that Nan in supraphysiological doses have the potential to offset or ameliorate conditions associated with enhanced proteolysis and disordered
protein turnover.