Reduction of Urea Generation and Muscle Protein Degradation by Adrenalectomy in Acutely Uremic Rats

The effect of adrenalectomy on the enhanced protein degradation in acute uremia was investigated. Therefore, serum urea nitrogen, urea N appearance and Nt-methylhistidine were followed in bilaterally nephrectomized rats. At 48 h after induction of uremia the animals displayed serum urea nitrogen levels of 223 ± 9.5 mg/dl as compared to 26.0 ± 1.0 mg/dl in sham-treated rats. This increment was significantly attenuated in acutely uremic, adrenalectomized animals (176 ± 6.0 mg/dl). When these rats were substituted with corticosterone (5 mg/kg body weight), serum urea nitrogen readily increased to levels of acutely uremic animals with intact adrenal glands (225 ± 6.0 mg/dl). The net generation of urea, as determined by the urea N appearance, was significantly increased during acute uremia (370 ± 26 mg/48 h) as compared to SHAM animals (220 ± 15 mg/48 h). This increment of urea formation could almost be completely reversed by simultaneous adrenalectomy (238 ± 20 mg/48 h). When these rats were substituted with corticosterone, the urea N appearance rebounded to values quite comparable to acutely uremic rats with intact adrenal glands (363 ± 30 mg/48 h). To determine whether skeletal muscle proteins might serve as a source for the enhanced protein degradation in acute uremia, plasma levels of N’-methylhistidine were measured. Bilaterally nephrectomized rats had Nt-methylhistidine values of 9.6 ± 1.0 μg/ml. In acutely uremic rats without adrenal glands, Nt-methylhistidine levels were found to be significantly decreased (6.0 ± 0.4 μg/ml). Substitution of corticosterone in these animals caused a remarkable rebound of Nt-methylhistidine values (9.2 ± 0.9 μg/ml). These results establish the capability of glucocorticoids to enhance protein degradation in acutely uremic rats. Moreover, this seems to be primarily brought about by an increment in myofibrillar protein breakdown.