Neuroadaptive Events In Adult Offspring Induced By Perinatal Chronic Stimulation Of The Renin-Angiotensin System (RAS).

ANTUNES-RODRIGUES, J; DADAM, FM; VIVAS, L.; MACCHIONE, AF

Chicago

Congreso; Experimental Biology Congress; 2017

Studies of last decades give evidence of the important role of the perinatal environment in the developing systems being able to result in permanent changes of the physiology and the metabolism of the new individual. Evidences from our and other laboratories indicate that mechanisms and circuits involved in the hydrosaline balance may be vulnerable to perinatal programming effects. This hydroelectrolytic-programming may be given by intrauterine and/or postnatal environment alterations. In this work, the programming model utilized was the chronic stimulation of RAS given by the partial aortic ligation (PAL) in dams before the matting and along the gestation and lactation. Water and sodium intake patterns and neuronal activity (Fos-ir, Fos-immunostaining) were investigated in adult offspring subject to a sodium depletion made with Furosemide (40mg/kg, sc) and low sodium diet [F/LSD]. Maternal fluid intake, plasma electrolyte levels and plasma renin activity (PRA) were also studied at weaning in mothers and female offspring. The perinatal programming groups (PP) were: i) PAL/hypertonic sodium solution/water [PAL]; ii) sham surgery/hypertonic sodium solution/water [Sh-Na] and iii) only water [Sh-W]. The PP started one week before mating and finished at weaning. PAL-dams showed an increased PRA levels and water and total fluid intakes, and a diminished in osmolality levels without being altered their natremia levels. The two last results probably were a consequence of the dipsogenic effect of the PAL model. In contrast, PAL-pups showed an increase in natremia and osmolality levels. Possibly, this plasma osmolyte accumulation in PAL pups may be origin by renal immaturity that leads to a deficient excretory function unable of eliminated the excess of circulating sodium. A decrease in water and sodium intake was observed in adult PAL-offspring subject to F/LSD. This behaviour was accompanied by an increase in the number of Fos-ir cells in the dorsal raphe nucleus. Because this nucleus is part of a circuit that tonically inhibits fluid intake, it is possible to assume that the decreased fluid intake in PAL-offspring may be due to a desensitization of this nucleus, preventing the normal triggering of the fluid ingestion response induced by F/LSD. These data shown neuroadaptive events, probably such as a consequence of long-term perinatal programming processes that affect reception of signals and activity of brain circuits involved in hydrosaline homeostasis and in fluid intake regulation.