Maternal Na⁺ intake induces renal function injury in rats prevented by a short‐term angiotensin converting enzyme inhibitor

Abstract

The Na -ATPase, a secondary pump in the proximal tubule, is only weakly responsive to angiotensin II in adult offspring exposed perinatally to high Na intake. We have investigated whether the offspring from mothers given 0.3 mol/L NaCl show an ineffective angiotensin II action to increase in blood pressure. It was hypothesized that functional alterations at adult life are associated with the number of angiotensin II-positive cells in the developing kidney, with increased oxidative stress in maternal/foetal organs, or with morphometrical changes in placentas. Wistar female rats were maintained on 0.3 mol/L NaCl in their drinking water from 20 days before conception until weaning. After weaning, some of the male offspring were treated with enalapril for 21 days. Glomerular filtration rate was recorded up to 210 days of age, when mean arterial pressure was measured after infusion of angiotensin II. To investigate the placenta and foetal kidneys, mothers on tap water or NaCl were also treated with alpha-tocopherol, pregnancy being interrupted on the 20th day. There were no changes in the number of cells positive for angiotensin II in the foetal kidney and unchanged lipid peroxidation in the placenta of offspring exposed to NaCl, but the intermediate trophoblast area in the junctional zone was increased, possibly reducing maternal-foetal exchange. Glomerular filtration rate was reduced and there was an attenuated effect of angiotensin II on elevation of blood pressure, which could be mediated by an elevated angiotensin II during early life, once these disturbances had been prevented by early and short-term treatment with enalapril.

Alpha‐Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring

“…With respect to oxidative stress (Figure ), saline decreased basal O 2 − production in the heart with no influence in kidneys, which matches with the lack of renal and tissular systemic oxidative lesions in the offspring whose mothers given saline overload during gestation . The observations regarding NADPH oxidase‐stimulated formation of O 2 − , stimulated by α‐Tocopherol in the heart but not in the kidney (regardless of the type of maternal liquid intake), suggest that the cardiac and renal actions of α‐Tocopherol do not involve the same mechanisms.…”

“…Modifications in the RAS for a short period just before or after weaning can change renal function in the longer term. Inhibition of RAS for short periods is sufficient to decrease blood pressure in SHR, as well as to the recovery of the normal activities of Na + ‐transporting ATPases in the renal proximal tubule and the control values of creatinine clearance (CrCl) in the offspring from mothers given salt overloading during gestation . A central role for RAS in the cardiovascular and renal effects of α‐Tocopherol received support in one of our studies, in which we demonstrated that maternal α‐Tocopherol during gestation programs retarded renal development in the pups (enlargement of the nephrogenic zone in kidneys of 1‐day‐old pups), as well as for altered expression of several components of the local renin/angiotensin system in both pups and juvenile rats (upregulation of Ang II receptors (AT 1 R and AT 2 R) and of several isoforms of PKC, a key element of AT 1 R‐linked signalling pathways) .…”

“…NaCl overload during gestation has been associated with the development of renal and cardiovascular dysfunctions . Of special interest is the observation that maternal high salt intake causes irreversible alterations in the geometry and composition of the central and peripheral vasculature before the onset of hypertension, even when the offspring are switched to a low NaCl intake after weaning …”