Preeclampsia induces the acquired salt‐sensitivity characteristics via increased vasopressin secretion in the postpartum stage

Abstract

BackgroundWomen with a history of preeclampsia exhibit increased salt‐sensitivity in the postpartum stage, which might account for their increased risk of future cardiovascular disease. However, it is unclear whether the increased salt‐sensitivity is a cause or effect of preeclampsia. Various factors, such as kidney injury and renin‐angiotensin system, are associated with salt‐sensitive hypertension. Vasopressin may also play a role in the pathogenesis of both preeclampsia and salt‐sensitive hypertension.PurposeThe aim of the present study was to investigate whether the onset of preeclampsia in subjects with originally normal salt‐sensitivity induces increased salt‐sensitivity in the postpartum stage, and to elucidate the possible mechanisms.Methods and ResultsWe used the reduced uterine perfusion pressure (RUPP) rat model, which is widely used as an acquired model of preeclampsia. Pregnant Sprague‐Dawley rats at day 14 of gestation were divided into two groups: RUPP‐operated (n=7) and sham‐operated (SHAM) controls (n=8). At 3 weeks postpartum, a high‐salt diet was initiated for 1 week. The high‐salt diet‐induced changes in mean arterial pressure (MAP) and the sodium sensitive index (SSI=ΔMAP/Δurine sodium) were significantly greater in the RUPP group than in the SHAM group (ΔMAP: 19.8±2.7 vs. 9.3±1.7 mmHg, SSI: 801±140 vs. 421±95.3 mmHg/mmol, both p<0.05). Creatinine clearance was not significantly different between groups, and histological studies revealed that both groups had normal kidney structures. Plasma renin activity and plasma aldosterone levels did not differ between groups. Levels of plasma copeptin, a substitute for plasma vasopressin, were significantly increased in the RUPP group compared with the SHAM group (150±20.3 vs. 98±18.6 pg/ml, p<0.05). Double immunofluorescence staining also revealed that expression of c‐Fos, a marker of neural activity, in vasopressin‐producing neurons was significantly increased in the hypothalamic paraventricular nucleus in the RUPP group compared with the SHAM group (% of c‐Fos positive neurons in vasopressin neurons: 45.8±7.1% vs. 23.1±2.0%, p<0.05). Gavage administration of the dual V1a/V2 vasopressin receptor antagonist conivaptan (1.0 mg/kg/day) while on the high‐salt diet attenuated the increase in MAP and decreased SSI in the RUPP rats (ΔMAP: 9.5±2.1 mmHg, SSI: 437±76.9 mmHg/mmol, n=4), but not in the SHAM rats (ΔMAP: 14.5±2.8 mmHg, SSI: 574±106 mmHg/mmol, n=5).ConclusionPreeclampsia caused salt‐sensitivity of blood pressure in the postpartum stage, probably due to increased vasopressin secretion.Support or Funding InformationKanae Foundation for the Promotion of Medical ScienceThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.