High sodium intake stimulates endogenous sodium pump inhibitor, marinobufagenin, and increases blood pressure in pregnant rats

Abstract

Previous studies have implicated endogenous digitalis-like sodium pump ligands in pathogenesis of preeclampsia. Recently, we have shown that an endogenous bufadienolide, marinobufagenin (MBG), an inhibitor of ouabain resistant alpha-1 Na/K-ATPase, rather than endogenous ouabain (EO) becomes elevated and contributes to hypertension in patients with preeclampsia (Lopatin et al, J Hypertens 1999; 17: 1179-87) and in Dahl-S rats on a high NaCl intake (Fedorova et al, Circulation 2002; 105: 1122-27). We hypothesized that in pregnant rats on a high NaCl intake MBG increases and contributes to blood pressure (BP) elevation. Renal excretion of MBG, EO and sodium, systolic BP, and plasma renin activity (PRA) were compared in non-pregnant and pregnant Sprague-Dawley rats (225-250 g) during last week of pregnancy. Pregnant animal consumed either water or NaCl solution, 0.9% or 1.8%. As compared with non-pregnant rats, last week of pregnancy was associated with decreased systolic BP, increased PRA and moderate increases in renal excretion of MBG and EO. NaCl supplementation induced graded increases in renal Na excretion, in systolic BP and renal excretion of MBG and with concomitant decrease in PRA (Table). Supplementation with 1.8% NaCl was also associated with fetal growth retardation. Our results demonstrate that in rats NaCl supplementation during the last week of pregnancy induces preeclampsia-like symptoms including elevation of BP, proteinuria, suppression of PRA and fetal growth retardation. Elevations of BP are associated with enhanced excretion of MBG, which makes MBG a potential target for therapy. One-way ANOVA followed by Newman-Keuls test. -P<0.05, -P<0.01 vs. nonpregnant rats; -P<0.05, -P<0.01 vs. pregnant rats without NaCl supplementation. n=12–15 for each group. One-way ANOVA followed by Newman-Keuls test. -P<0.05, -P<0.01 vs. nonpregnant rats; -P<0.05, -P<0.01 vs. pregnant rats without NaCl supplementation. n=12–15 for each group.