Physiological and Molecular Responses to Altered Sodium Intake in Rat Pregnancy

• Published in: Journal of the American Heart Association 2018-08, Vol.7 (15), p.e008363-e008363
• Main Authors: Eisele, Nicole, Klossner, Rahel, Escher, Geneviève, Rudloff, Stefan, Larionov, Alexey, Theilig, Franziska, Mohaupt, Markus G, Mistry, Hiten D, Gennari-Moser, Carine
• Format: Article
• Language: English
• Subjects: Angiotensins - drug effects; Angiotensins - genetics; Animals; Blood Pressure - drug effects; Diet, Sodium-Restricted; Drinking Behavior - drug effects; Eating - drug effects; Epithelial Sodium Channels - drug effects; Epithelial Sodium Channels - genetics; Female; ion transport; kidney; Kidney - drug effects; Kidney - metabolism; Original Research; Peptidyl-Dipeptidase A - drug effects; Peptidyl-Dipeptidase A - genetics; physiology; Pregnancy; Rats; Rats, Sprague-Dawley; Receptors, Angiotensin - drug effects; Receptors, Angiotensin - genetics; renin angiotensin system; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - genetics; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Sodium, Dietary - pharmacology; Telemetry; Water; Water-Electrolyte Balance - drug effects
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.117.008363

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.