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.