Abstract-A successful pregnancy requires an accommodating environment. Salt and water availability are critical for plasma volume expansion. Any changes in sodium intake would alter aldosterone, a hormone previously described beneficial in pregnancy. To date, it remains ambiguous whether high aldosterone or high salt intake is preferable. We hypothesized that increased aldosterone is a rescue mechanism and appropriate salt availability is equally effective in maintaining a normotensive blood pressure (BP) phenotype in pregnancy. We compared normotensive pregnant women (n=31) throughout pregnancy with young healthy female individuals (n=31-62) and performed salt sensitivity testing within the first trimester. Suppression of urinary tetrahydro-aldosterone levels by salt intake as measured by gas chromatography-mass spectrometry and urinary sodium excretion corrected for creatinine, respectively, was shifted toward a higher salt intake in pregnancy (P<0.0001). In pregnancy, neither high urinary tetrahydro-aldosterone nor sodium excretion was correlated with higher BP. In contrast, in nonpregnant women, systolic BP rose with aldosterone (P<0.05). Testing the impact of salt on BP, we performed salt sensitivity testing in a final cohort of 19 pregnant and 24 nonpregnant women. On salt loading, 24-hour mean arterial pressure rose by 3.6±1.5 and dropped by -2.8±1.5 mm Hg favoring pregnant women (P<0.01; χ 2 =6.04; P<0.02). Our data suggest first that salt responsiveness of aldosterone is alleviated in conditions of pregnancy without causing aldosterone-induced hypertension. Second, salt seems to aid in BP lowering in pregnancy for reasons incompletely elucidated, yet involving renin suppression and potentially placental sensing mechanisms. and Blood Pressure in Pregnancy 363a homozygous loss-of-function mutation of the CYP11B2 on salt supplementation. 13To date, it remains uncertain whether high aldosterone levels and high salt intake are preferable in pregnancy. Given the current evidence, we hypothesized first that increased aldosterone is a rescue mechanism to maintain a BP reasonable for pregnancy, and second that appropriate salt availability is required to maintain a normotensive BP phenotype in pregnancy. As a corollary, inappropriately low aldosterone levels for a given gestational age might be counterbalanced by increased salt availability, thus substituting for the missing aldosterone effect. To verify our hypothesis, we have first studied the BP in women along pregnancy as related to salt intake and aldosterone levels and then compared first trimester salt sensitivity in pregnant women with young female nonpregnant individuals. Methods PatientsA first set of pregnant women from the Bernese pregnancy registry and nonpregnant women matched for age with a complete prospective sampling of serum and urine was used for the study. Clinical data were collected prospectively including standardized measurement of office BP and pregnancy outcome. Only normotensive pregnant women were included in the analysis. Visits we...

Glucagon-like peptide 1 (GLP-1) and oxyntomodulin (OXM) are structurally related gastrointestinal hormones that are secreted in response to food intake. They reduce food intake and body weight and exert partly overlapping actions on glucose homeostasis and gastrointestinal function. The hypothalamic arcuate (ARC) nucleus is among the central structures expressing a high density of GLP-1 receptors (GLP-1R), which are known to be activated by both peptides. It was the aim of our electrophysiological studies to characterize the effects of GLP-1 and OXM on functionally defined ghrelin-sensitive ARC neurons. GLP-1 and OXM (10(-7) M) exerted excitatory effects in about two-thirds of ghrelin-inhibited neurons and in approximately one-third of ghrelin-excited cells. In addition, a minor fraction of the ghrelin-excited cells was inhibited by both peptides. There was a high degree of cosensitivity to GLP-1 and OXM, and the effects of both hormones were blocked by the GLP-1R antagonist exendin(9-39). The GLP-1R-mediated excitations and inhibitions persisted under synaptic blockade, indicating a direct postsynaptic mode of action. Our results demonstrate that GLP-1 and OXM directly and similarly alter neuronal activity in the ARC, probably via a common GLP-1R-mediated mechanism. Ghrelin-antagonistic effects on neuronal activity, which might be implicated in ghrelin-antagonistic in vivo actions, resulting from GLP-1R stimulation (e.g., GLP-1R dependent supression of food intake), predominated in ghrelin-inhibited ARC neurons. However, a subset of ghrelin-excited ARC neurons showed responses to OXM or GLP-1, suggesting the existence of a common mode of action for these hormones; the functional relevance of this effect remains to be elucidated.

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BackgroundNormal pregnancy depends on pronounced adaptations in steroid hormone concentrations. Although in recent years, the understanding of these hormones in pregnancy has improved, the interpretation is hampered by insufficient reference values. Our aim was to establish gestation-specific reference intervals for spot urinary steroid hormone levels in normal singleton pregnancies and 6 weeks postpartum.MethodsCross-sectional multicentre observational study. Women recruited between 2008 and 2013 at 3 University Hospitals in Switzerland (Bern), Scotland (Glasgow) and Austria (Graz). Spot urine was collected from healthy women undergoing a normal pregnancy (age, 16–45 years; mean, 31 years) attending routine antenatal clinics at gestation weeks 11, 20, and 28 and approximately 6 weeks postpartum. Urine steroid hormone levels were analysed using gas-chromatography mass spectrometry. Creatinine was also measured by routine analysis and used for normalisation.ResultsFrom the results, a reference interval was calculated for each hormone metabolite at each trimester and 6 weeks postpartum. Changes in these concentrations between trimesters and postpartum were also observed for several steroid hormones and followed changes proposed for index steroid hormones.ConclusionsNormal gestation-specific reference values for spot urinary steroid hormones throughout pregnancy and early postpartum are now available to facilitate clinical management and research approaches to steroid hormone metabolism in pregnancy and the early postpartum period.

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BackgroundIn 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.ConclusionsPregnancy 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.