The modulatory effect of adrenaline on development of steroid myopathy induced by chronic administration of hydrocortisone in white rats

Abstract

Based on the beneficial effect of chronic adrenergic stimulation on the neuromuscular apparatus function, the aim of this study was to evaluate efficacy of adrenaline at therapeutic doses in compensation for adverse effects of chronically administered hydrocortisone on mixed-fiber type skeletal muscles (m. tibialis anterior). Method. Experiments were performed on sexually mature female rats (190—220 g) divided into 3 groups: control (n = 10), experimental group 1 (H group, n = 10, hydrocortisone acetate, for 30 days daily), and experimental group 2 (H+A group, n = 10, hydrocortisone acetate in combination with adrenaline hydrochloride, for 30 days daily). Hydrocortisone acetate (Farmak, Ukraine) was injected i.p. at a dose of 0.2 mg/kg, which was equivalent to the human therapeutic dose of 3 mg/kg. Adrenaline hydrochloride (Zdorovje, Ukraine) was injected s.c. at a dose of 0.2 mg/kg. Parameters of the tibialis anterior muscle function were studied on anesthetized animals (sodium thiopental, 100 mg/kg) using electromyography and myography methods. Muscle contractions were induced by suprathreshold electrical stimulation of the fibular nerve. Results. Chronic administration (30 days) of hydrocortisone caused symptoms of steroid myopathy evident as low-amplitude M-waves of normal duration, increased frequency of polyphase potentials (by 30%), decreased quantity of activated motor units (by 33%), and decreased muscle mass (by 14%). Hydrocortisone-induced hypercorticoidism was associated with prolonged latent period (by 37%) and shortening phase (by 20%) and decreased amplitude (by 32%), amount of muscular external work (by 40%) in a single tibialis anterior muscle contraction, and decreased muscular power (by 41%) developed in a tetanic contraction. Following repeated hydrocortisone injections, the overall process of neuromuscular transmission was disturbed, which was evident as its impaired reliability (30% of rats) and pronounced facilitation (>85% in 50% of rats) or depression (<-42% in 40% of rats) at an optimum stimulation frequency (30 imp/s). Adrenaline administered in combination with hydrocortisone prevented formation of myopathy symptoms, such as decreases in the M-wave amplitude, number of activated motor units, muscle weight, external work and power, and it also decreased the frequency of polyphase M-waves (from 30% to 10%). In addition, adrenaline attenuated the adverse effect of hydrocortisone on the synaptic apparatus by decreasing the incidence of reduced reliability of synaptic transmission (from 30% to 10%), facilitation (from 50% to 20%), and depression (from 40% to 10%) in the H+A-group compared to the H group. Conclusion. The experimental data obtained in model experiments on animals in situ support the adrenaline ability to effectively compensate for a number of adverse effects of chronic hydrocortisone treatment on the skeletal muscle.