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INTRODUCTION AND AIMS: Pregnancy associates with hormonal alterations including prolactin rise, which influence maternal kidney functions. Cholestasis of pregnancy is the most common pregnancy disorder, which induces additional elevation of prolactin level. Under condition of hyperprolactinemia evolutionally ancient prolactin functions such as water-salt balance regulation can be manifested. Kidneys play a key role in the maintenance of systemic acid-base balance including bicarbonate biodynamics. Our aim was to study prolactin participation in the bicarbonate balance regulation in the rat model of cholestasis of pregnancy. METHODS: The follows groups of female rats were used: intact, pseudopregnant due to hyperprolactinemia induced by pituitary transplantation under renal capsule; rats with cholestasis induced by common bile duct ligation; pseudopregnant with cholestasis (the model of cholestasis of pregnancy). Water consumption, diuresis, GFR, and bicarbonate concentration in urine, blood and bile as well as bicarbonate excretion and reabsorption were determined. RESULTS: Daily diuresis and compensatory water consumption were elevated in the model of cholestasis of pregnancy. Diuresis elevation was not due to GFR increase since creatinine clearance was not changed. Cholestasis induced two fold elevation of dairy bicarbonate excretion as compared with intact females (p<0.05). In the model of cholestasis of pregnancy additional 2.4 fold increase of bicarbonate excretion was observed (p<0.05). Daily clearance of bicarbonates was also elevated both under hyperprolactinemia and cholestasis conditions as compared with intact rats (p<0.05). Combination of these conditions in the model of cholestasis of pregnancy leads to additional two fold rise of bicarbonate clearance related to control groups. Calculation of bicarbonate reabsorption demonstrated its decrease to similar level under condition of hyperprolactinemia and cholestasis and additional decline in the model of cholestasis of pregnancy (p<0.05). Serum bicarbonate concentration was decreased by nearly 25% under hyperprolactinemia conditions. We can’t find any alterations in bile bicarbonate concentration in all investigated groups. In the model of cholestasis of pregnancy prolactin exerts natriuretic action [1, 2]. Under hyperprolactinemia conditions bicarbonate clearance significantly correlated with sodium ion clearance. CONCLUSIONS: Hyperprolactinemia in the model of cholestasis of pregnancy stimulates both bicarbonate and sodium excretion, suggesting its interconnection. Effect of prolactin may be direct and release though renal prolactin receptor or may be indirect and due to prolactin regulation of other hormones, controlling water-salt balance. Thus, under conditions of physiological and pathological hyperprolactinemia prolactin participation in renal water-salt balance regulation becomes much more evident. 1. Crambert S., Sjöberg A., Eklöf A.-C. et al. Am. J. Physiol. Renal Physiol. 2010. V. 299. № 1. P. F49-54. 2. Fidchenko Yu. M., Kushnareva N. S., and Smirnova O. V. Byulleten’ Eksperimental’noi Biologii I Meditsiny, Vol. 156, No. 12, pp. 767-770, 2013.