Physiological and molecular responses to altered sodium intake in rat pregnancy

Abstract

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 ENaC activation and consecutive Na+ retention.