Physiological and Molecular Responses to Altered Sodium Intake in Rat Pregnancy

Background In pregnancy, a high plasma volume maintains uteroplacental perfusion and prevents placental ischemia, a condition linked to elevated maternal blood pressure ( BP ). Reducing BP by increasing Na⁺ intake via plasma volume expansion appears contra-intuitive. We hypothesize that an appropriate Na⁺ intake in pregnancy reduces maternal BP and adapts the renin-angiotensin system in a pregnancy-specific manner. Methods and Results BP was measured by implanted telemetry in Sprague-Dawley rats before and throughout pregnancy. Pregnant and nonpregnant animals received either a normal-salt (0.4%; NS ), high-salt (8%; HS ), or low-salt (0.01%; LS ) diet, or HS (days 1-14) followed by LS (days 14-20) diet ( HS / LS ). Before delivery (day 20), animals were euthanized and organs collected. Food, water, and Na⁺ intake were monitored in metabolic cages, and urinary creatinine and Na⁺ were analyzed. Na⁺ intake and retention increased in pregnancy ( NS , LS ), leading to a positive Na⁺ balance ( NS , LS ). BP was stable during LS , but reduced in HS conditions in pregnancy. The renin-angiotensin system was adapted as expected. Activating cleavage of α- and γ-subunits of the renal epithelial Na⁺ channel and expression of-full length medullary β-subunits, accentuated further in all LS conditions, were upregulated in pregnancy. Conclusions Pregnancy led to Na⁺ retention adapted to dietary changes. HS exposure paradoxically reduced BP . Na⁺ uptake while only modestly linked to the renin-angiotensin system is enhanced in the presence of posttranslational renal epithelial Na⁺ channel modifications. This suggests (1) storage of Na⁺ in pregnancy upon HS exposure, bridging periods of LS availability; and (2) that potentially non-renin-angiotensin-related mechanisms participate in EN aC activation and consecutive Na⁺ retention.