Prior Exposure to Preeclampsia Causes Increased Salt Sensitivity of Blood Pressure at Postpartum through Vasopressin Production and Secretion

Background Women with a history of preeclampsia exhibit increased salt sensitivity of blood pressure in postpartum period, which might be responsible for their increased risk of future cardiovascular diseases. However, it is unclear whether preeclampsia can cause the increased salt sensitivity at postpartum. Vasopressin may play a role in the pathogenesis of both preeclampsia and salt‐sensitive hypertension. Therefore, the aim of this study was to determine whether the exposure to preeclampsia causes the increased salt sensitivity of blood pressure at postpartum, and if so, whether vasopressin is involved in its process. Methods and Results We used a reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. Pregnant Sprague–Dawley rats were divided into two groups; RUPP‐operated and sham‐operated (SHAM) control groups. A 1‐week‐long high‐salt diet was initiated at 3 weeks postpartum and the rats were sacrificed at 4 weeks postpartum. The high‐salt diet‐induced increase in mean arterial pressure (MAP) was significantly greater in the RUPP group than in the SHAM group (14.9 ± 2.5 vs 6.5 ± 1.6 mmHg, n=8 and 9, P<0.05). Further, plasma levels of copeptin, a substitute for vasopressin, were increased (150.1 ± 20.3 vs 87.9 ± 19.1 pg/mL, n=7 and 8, P<0.05) and serum osmolality was decreased (299.0 ± 1.4 vs 304.4 ± 1.3 mOsm/L, n=9 and 10, P<0.05) in the RUPP group. The baseline MAP and urine copeptin before salt loading were not different between groups. Immunostaining of hypothalamic paraventricular nucleus revealed that expression of c‐Fos, a marker of neural activity, was significantly increased in vasopressin‐producing neurons within the magnocellular region and presympathetic neurons within the parvocellular region in the RUPP group. The ratio of low frequency/high frequency components (LF/HF) from power spectrum analysis of heart rate variability, an index of sympathetic activity, significantly increased after salt loading in the RUPP group (after salt loading vs baseline, 1.01 ± 0.15 vs 0.40 ± 0.04, n=8, P<0.05), but not in the SHAM. Renal cortex norepinephrine levels also tended to be higher in the RUPP group than in the SHAM (5.50 ± 0.53 vs 4.21 ± 0.49 ng/mg, n=8 and 9, P=0.09). There was no significant difference in urine protein and creatinine clearance between the RUPP and SHAM groups. Renal histological staining revealed normal kidney structure in both groups. Plasma renin activity and plasma aldosterone levels were not significantly different between groups after salt loading. The oral administration of conivaptan (1.0 mg/kg/day), the dual V1a/V2 vasopressin receptor antagonist, during high‐salt diet abolished the enhanced increase in MAP, c‐Fos expression within the parvocellular region of paraventricular nucleus, LF/HF from power spectrum analysis, and kidney norepinephrine levels in the RUPP rats. Conclusion Prior exposure to preeclampsia causes increased salt sensitivity of blood pressure at postpartum probably due to enhanced vasopressin secretion and sympathoexcitation in response to salt loading. Support or Funding Information Kanae Foundation for the Promotion of Medical Science, Takeda Science Foundation This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .