Abstract P232: Pregnancy Induced Changes In Urinary Uromodulin Excretion In Normotensive And Chronic Hypertensive Rodent Models

Abstract

Hypertensive disorders complicate 1-4% of pregnancies and are the leading cause of maternal death. Pregnancy involves major adaptions in renal hemodynamics, tubular and endocrine functions. Uromodulin (UMOD) is a renal protein that plays a role in renal sodium and divalent cation transport and is associated with hypertension and kidney diseases. We aimed to understand the role of blood pressure (BP) in urinary UMOD excretion during pregnancy. Pregnant Wistar Kyoto (WKY) and Stroke Prone Spontaneously Hypertensive (SHRSP) rats (n=8) were studied for 18.5 gestational days (GD). A group of pregnant SHRSP were treated with the beta-blocker propranolol (100mg/kgBW/day; n=8) and the calcium channel blocker nifedipine (25mg/kgBW/day; n=7) from GD 0.5. Systolic BP (SBP; tail cuff plethysmography), urine and plasma characteristic were monitored at baseline, GD3.5, GD12.5 and GD 18.5. UMOD concentration were measured in 24hr urine with ELISA. Pregnant SHRSP were hypertensive throughout the gestation compared to WKY (delta SBP 22.6 ± 3.6 mmHg, p<0.0001). At baseline (pre-pregnancy), urinary UMOD levels were 2-fold higher in WKY compared to SHRSP (p<0.05). During pregnancy, the urinary UMOD gradually decreased in WKY (2-fold decrease, p<0.05), whereas a 1.5-fold increase (p<0.05) was observed in hypertensive SHRSP compared to pre-pregnancy. The changes observed in urinary levels corresponded to total kidney UMOD levels at GD18.5, wherein SHRSP kidney shows 1.3-fold (p<0.01) greater expression of UMOD compared to WKY. Nifedipine reduced BP in pregnant SHRSP (delta SBP between GD18.5 and baseline: 44.3 ± 7.4 mmHg, p<0.0001) while propranolol did not affect BP. However, neither nifedipine nor propranolol changed urinary UMOD excretion in pregnant SHRSP. BP was not significantly correlated with urinary uromodulin levels in pregnant WKY (Pearson, r=-0.01, p 0.95) and SHRSP without (r=-0.16, p 0.46) or with (nifedipine r=0.26, p 0.31; propranolol r=0.17, p 0.45) antihypertensive treatment. We demonstrate differences in UMOD excretion between hypertensive and normotensive pregnancy and changes during pregnancy that are at least in part BP independent. Our data provide novel insights into molecular changes associated with hypertensive pregnancy.