Effects of dehydration on endocrine regulation of the electrolyte and fluid balance and atrial natriuretic peptide-binding sites in perinatally malnourished adult male rats.

OBJECTIVE The first aim of this work was to investigate, under basal conditions in adult male rats, the long-term consequences of perinatal maternal food restriction on the plasma concentrations of vasopressin (VP), aldosterone and atrial natriuretic peptide (ANP) and on plasma renin activity (PRA). Furthermore, under these same conditions, the hypothalamic VP gene expression as well as the density (B(max)), affinity (K(d)) and gene expression of ANP receptors were determined in kidneys and adrenals. The second aim of this work was to examine the responsiveness to dehydration in perinatally malnourished rats. Thus, the latter parameters were studied in these rats after 72 h water deprivation. METHODS This study was conducted on 4-Month-old male rats from mothers exposed to 50% food restriction (FR50) during the last week of gestation and lactation and on age-matched control animals (C). At this stage, both C and FR50 rats were killed by decapitation between 0900 h and 1000 h in order to determine parameters under basal conditions or after 72 h water deprivation. Plasma VP, ANP and aldosterone levels and PRA were determined by radioimmunoassay. Hypothalamic VP gene expression was determined in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by in situ hybridization. The B(max) and K(d) values of ANP receptors were evaluated from Scatchard plots. ANP receptor gene expression was determined by Northern blot analysis. RESULTS Under basal conditions, perinatal malnutrition reduced body weight, absolute weight of kidneys and adrenals, and haematocrit. Compared with control rats, FR50 rats had significantly greater plasma VP and aldosterone levels but PRA, plasma ANP levels, plasma osmolality and hypothalamic VP gene expression were not significantly different. Perinatal malnutrition did not significantly affect glomerular ANP receptor density, but in adrenals it decreased both B(max) and K(d) values of ANP-B receptors (biological receptors) and increased B(max) of ANP-C receptors (clearance receptors). ANP-B(A) (receptor subtype A of ANP-B receptors) receptor gene expression was not significantly affected, whereas ANP-C receptor gene expression was enhanced in both adrenals and kidneys in FR50 rats. After 72 h dehydration, control rats showed a significant rise in haematocrit, plasma osmolality, PRA, circulating levels of VP and aldosterone and VP gene expression in both PVN and SON but showed a decrease in plasma ANP levels. B(max) of ANP-B receptors was decreased whereas B(max) of ANP-C receptors was enhanced in both adrenals and kidneys. ANP-B(A) receptor gene expression was not significantly affected in either kidneys or adrenals in dehydrated control rats. Similarly, ANP-C receptor gene expression was unaffected in kidneys whereas it was significantly enhanced in adrenals. In FR50 rats, the effects of water deprivation were qualitatively similar to those reported in controls concerning plasma parameters except for plasma VP levels which tended to rise (not significant) but this increase was only very slight compared with controls. Moreover, unlike controls, VP gene expression in both PVN and SON was not enhanced after dehydration in FR50 rats. In kidneys, dehydrated FR50 rats, like controls, upregulated ANP-C receptors, but they were unable to downregulate ANP-B receptors. In adrenals, unlike controls, FR50 rats enhanced ANP-B receptor density whereas they decreased both ANP-C receptor density and expression after 72 h dehydration. Similar to controls, the expression of ANP-B(A) receptors in both kidneys and adrenals as well as the expression of ANP-C receptors in kidneys, were unaffected in dehydrated FR50 rats. CONCLUSION Perinatal malnutrition had long-lasting effects on regulation of the fluid and electrolyte balance under basal conditions. The main effects were a significant rise in circulating levels of VP and aldosterone, and changes in density of adrenal ANP-binding sites and ANP-C receptor gene expression in both adrenals and kidneys. Perinatal malnutrition also affects the responsiveness to water deprivation with alterations in both hypothalamic VP gene expression and regulation of ANP-binding sites.