Effects of oxytocin administration on the hydromineral balance of median eminence-lesioned rats.

Abstract

In the clinical setting, acute injuries in hypothalamic mediobasal regions, along with polydipsia and polyuria, have been observed in patients with cerebral salt wasting (CSW). CSW is also characterised by hypovolaemia and hyponatraemia as a result of an early increase in natriuretic peptide activity. Salt and additional amounts of fluid are the main treatment for this disorder. Similarly, experimental lesions to these brain regions, which include the median eminence (ME), produce a well-documented neurological model of polydipsia and polyuria in rats, which is preceded by an early sodium excretion of unknown cause. In the present study, oxytocin (OT) was used to increase the renal sodium loss and prolong the hydroelectrolyte abnormalities of ME-lesioned animals during the first few hours post-surgery. The objective was to determine whether OT-treated ME-lesioned animals increase their sodium appetite and water intake to restore the volume and composition of extracellular body fluid. Electrolytic lesion of the ME increased water intake, urinary volume and sodium excretion of food-deprived rats and also decreased urine osmolality and estimated plasma sodium concentration. OT administration at 8hours post-surgery reduced water intake, urine output and plasma sodium concentration and also increased urine osmolality and urine sodium excretion between 8 and 24hours post-lesion. From 24 to 30hours, more water and hypertonic NaCl was consumed by OT-treated ME-lesioned rats than by physiological saline-treated-ME-lesioned animals. Food availability from 30 to 48hours reduced the intake of hypertonic saline solution by ME/OT animals, which increased their water and food intake during this period. OT administration therefore appears to enhance the natriuretic effect of ME lesion, producing hydroelectrolyte changes that reduce the water intake of food-deprived animals. Conversely, the presence of hypertonic NaCl increases the fluid intake of these animals, possibly as a result of the plasma sodium depletion and hypovolaemic states previously generated. Finally, the subsequent increase in food intake by ME/OT animals reduces their need for hypertonic NaCl but not water, possibly in response to osmotic thirst. These results are discussed in relation to a possible transient activation of the ME with the consequent secretion of natriuretic peptides stored in terminal swellings, which would be augmented by OT administration. Electrolytic lesion of the ME may therefore represent a useful neurobiological model of CSW.