Effects of alfacalcidol on the contractile properties of the gastrocnemius medialis muscle in adult and old rats.

Vitamin D deficiency is associated with muscle weakness. It is unknown, however, how supra-physiological levels of vitamin D affect skeletal muscle. To investigate the effects of increased serum vitamin D (1,25 (OH)2D3 or 1,25D) levels on the contractile properties of the medial gastrocnemius muscle, adult and old female Fischer344 x Brown Norway F1 rats were orally treated with vehicle or the vitamin D analogue alfacalcidol for 1 or 6 weeks. Alfacalcidol treatment resulted in elevated 1,25D serum levels. This was accompanied by hypercalcaemia and a reduction in body mass, the latter largely attributable to a reduced food intake. However, kidney function, as reflected by normal creatinine serum levels, as well as heart mass were unaffected. The 17% reduction in maximal isometric force and power was explicable by a similar loss of muscle mass. The force-frequency relationship of the 6-week-treated old rats was shifted to the left, but neither the shape of the force-velocity relationship nor the fatigability of the muscle were altered. Supra-physiological doses of vitamin D were accompanied by significant reductions in body and muscle mass, but not by an improvement in muscle functioning. Weight loss was largely due to a reduced food intake, while the left shift in the force-frequency relation may be due to increased 1,25D levels.

Oxisuran and immune reactions: mediation of oxisuran action by the adrenal glands.

Oxisuran was tested in a TAR system and for the DH on SRBC. Besides immunosuppressive properties in the TAR and DH also mentioned by other authors, stimulation was found after prolonged administration. No effect of oxisuran on the humoral response was observed. The action of oxisuran was suggested to be indirect, effected by stimulation of the PAG system. Adrenalectomy of mice made animals non-liable for oxisuran action measured in the TAR assay. Oxisuran caused an increase of the corticosterone plasma level with a peak after four daily injections. This was paralleled by a peak in adrenal gland weight and a minimum in thymus size. The reduction in these effects after five injections (tachyphylaxis) suggest that a feedback mechanism is involved. Comparison of thymus weights after oxisuran and corticosterone administration indicates that a daily dose of 100 mg oxisuran/kg corresponds with 1.5 mg corticosterone/kg. The effects of oxisuran in the TAR and on the DH and the feedback phenomenon could be imitated with 1.5 mg corticosterone/kg. The mononuclear phagocyte has been proposed as the main target cell of oxisuran action, mediated by the PAG system.