Differential roles of VPS and RAAS in water homeostasis and a risk for kidney dysfunction in rats undergoing rapid fasting/dehydration with regular exercise

PURPOSE We examined the effects of rapid restriction of food and fluid intake on the pathways of water homeostasis, the vasopressinergic system (VPS), and the renin-angiotensin-aldosterone system (RAAS), in rats with or without regular exercise. METHODS Sprague Dawley rats were divided into the following groups: no intervention, rapid restriction, regular exercise, and rapid restriction combined with regular exercise. Rats in the exercise group performed climbing exercise for 4 weeks. All rats consumed food ad libitum, and those in the rapid restriction group fasted for the last 3 days with no water on the last 1 day. RESULTS Despite no significant differences in body weight among the groups, the kidney weight was decreased when rapid restriction and regular exercise were combined. Rapid restriction reduced the urine volume and increased the urine osmolality, whereas regular exercise did not. Rapid restriction but not regular exercise increased the levels of circulating aldosterone and the renal expression levels of the ion channel SGK-1 compared to those without rapid restriction, indicating the stimulation of RAAS. Conversely, VPS showed no significant response to these interventions. Moreover, rapid restriction combined with regular exercise induced the renal expression levels of proinflammatory cytokines and increased the active forms of apoptotic effector caspase-3 compared with the no intervention group. CONCLUSIONS Functional significance may differ between VPS and RAAS in water homeostasis in response to rapid restriction. Moreover, the combination of rapid restriction and regular exercise has potentially deleterious effects on the kidney.