gms | German Medical Science

Objectives: Mild hyponatremia (HypoNa) is a common electrolyte disorder in the clinical practice that is often not treated. However, it is associated with low muscle mass and physical function impairment. A common cause of HypoNa is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Estrogen deficiency following menopause in women is related to decreased muscle mass and strength. The effect of HypoNa on muscle was studied and compared with estrogen depletion in two respective rat models.

Methods: The SIADH rat model was applied to induce HypoNa (<135 mmol/L) in rats by treating them with desmopressin (5 ng/h, via s.c osmotic pumps). Ovariectomized rat was used as a postmenopausal model. Seven-month old female Sprague Dawley rats were divided into three groups (n=6): (1) intact normonatremic rats (NormoNa), (2) intact hyponatremic rats treated with desmopressin (HypoNa), (3) ovariectomized normonatremic rats (OVX). The pumps were replaced after 6 weeks. After 12 weeks of treatments, gastrocnemius (GM), soleus (SM) and longissimus (LM) muscles were analyzed by histological and enzyme analyses. Gene expression analysis was performed in GM. ANOVA and Tukey test were applied for statistical analyses (p<0.05).

Results and conclusion: After 12 weeks, OVX was confirmed by the reduced uterus weight (OVX: 0.17+0.04 g; other groups: 0.69+0.17 g) and HypoNa by low serum sodium levels (HypoNa: 110+3 mmol/L, other groups: 141+2 mmol/L). Body weight and muscle fiber size were increased in the OVX and HypoNa groups compared to the NormoNa group. A possible explanation for the increased body weight is that hormone deficiency after OVX increased abdominal fat and muscle fat content, and water retention in the HypoNa group increased heart, kidney, and SM weight. The HypoNa effect was stronger than OVX, enlarging cross-sectional areas of oxidative and intermediate fibers. Glycolytic fibers were not affected by OVX in LM or by both treatments in GM. Lactate dehydrogenase activity and nucleus density were elevated after OVX in GM. Desmopressin acts as a selective agonist at vasopressin receptors and in this study, it reduced the expression of vasopressin receptors. Angiogenic factor (VEGF-B) expression was decreased under HypoNa and increased under estrogen deficiency. Since overexpression of vasopressin receptors is known to improve atrophied muscle regeneration, their decreased expression along with low VEGF-B and enhanced myostatin expression could cause muscle impairment in the HypoNa rats. In conclusion, both OVX and desmopressin-induced HypoNa impaired muscle tissue. Ovx showed a known effect of hormone deficiency on muscle. HypoNa effect was presumably mediated directly through muscle vasopressin receptors and indirectly through low sodium levels. Further studies may reveal whether treatment against HypoNa help to improve muscle tissue.