Abstract
The aim of this work was to study the effect of a high sodium (HS) diet on blood pressure and renal function in male adult rats that have been treated with a dual Endothelin receptor antagonist (ERA) during their early postnatal period (day 1 to 20 of life). Male Sprague-Dawley rats were divided in four groups: CNS: control rats with normosodic diet; ERANS: ERA-treated rats with normosodic diet; CHS: control rats with high sodium diet; ERAHS: ERA-treated rats with HS diet. Systolic blood pressure (SBP) was recorded before and after the diet and 24-hour metabolic cage studies were performed. AQP2 and α-ENac expressions were measured by western blot and real time PCR in the renal medulla. Vasopressin (AVP) pathway was evaluated by measuring V2 receptor and adenylyl cyclase 6 (AC6) expression and cAMP production in the renal medulla. Pre-pro ET-1mRNA was also evaluated in the renal medulla. Only rats that had been treated with an ERA during their postnatal period increased their SBP after consumption of a HS diet, showing an impaired capacity to excrete sodium and water, i.e. developing salt sensitivity. This salt sensitivity would be mediated by an increase in renomedullary expression and activity of AQP2 and α-ENaC as a consequence of increased AC6 expression and cAMP production and/or a decreased ET-1 production in the renal medulla. The knowledge of the molecular mechanisms underlying the perinatal programming of salt sensitive hypertension will allow the development of reprogramming strategies in order to avoid this pathology.
Highlights
The developing embryo and/or fetus is highly sensitive to perturbations of the maternal environment
There was a significant increase in renal weight expressed as g/100g of body weight in both CHS and ERAHS when compared with their respective normal sodium diet (NS) controls (p
Food intake, expressed per 100g b.w. was similar in all groups of rats, suggesting that the differences seen in blood pressure were not due to different sodium intakes
Summary
The developing embryo and/or fetus is highly sensitive to perturbations of the maternal environment. The developing organs can mount an adaptive response in order to ensure survival and the maintenance of critical functions of the tissues. These adaptive responses may represent an increased risk for diseases later in life; a process known as “Disease programming” [3]. Bearing in mind that renal development in rodents continues along the early postnatal period, the fetus is at a risk for developmental disease programming, and the neonate. We have shown previously that the inhibition of ET system in the rat with a dual ET receptor antagonist (ERA) during the early postnatal period affects both renal structure and function, decreasing the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increasing the proteinuria, being these effects more pronounced in male rats [9]. Brenner and colleagues postulated that reduced filtration surface area associated with a low nephron number would lead to sodium retention and development of systemic hypertension as a compensatory response to maintain sodium homeostasis [10, 13, 14]
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