Renal epithelial sodium channel (ENaC) is required for blood pressure (BP) maintenance in pregnant rat

Abstract

To define the molecular mechanisms responsible for Na retention, plasma volume expansion (PVE) and BP maintenance in pregnancy, we studied virgin (V), mid pregnant (MP, day 13/14) and late pregnant (LP, day 19/20) rats. We previously found αENaC (the rate limiting subunit for channel formation) is upregulated in MP and LP rats and in vivo ENaC activity (natriuretic response to ENaC blockade with benzamil (Bz), 0–3 hour urine collection) is increased in MP and LP vs V rats. To assess the importance of ENaC activity for these adaptations in pregnancy, P rats were placed on chronic Bz (iv via perfusion pump, 0.7 or 1.05 mg/kg adjusted to account for PVE as pregnancy progresses). This prevented the increase in in vivo ENaC activity in MP (MP=361±92; time control V=388±60 μM/hr, NS) and LP (LP=585±100; time‐control V=663±194 μM/hr, NS) rats. Compared to control rats, Bz reduced PV by 0.92±0.16 ml (p<0.05) in MP rats and by 0.697±0.13 ml in LP rats. Bz reduced BP (radio‐telemetry) in LP rats by 29.9±9.4 mmHg ( p<0.05) but not in V rats. LP rats receiving mineralocorticoid receptor (MR) blockade with eplerenone (epl) overnight, net UNaV was decreased to V levels (LP + epl=571±172, V=368±64, normal LP=985±118 * μM/hr, *=p<0.05 V vs normal LP). These data suggest that ENaC activity is required for PVE and BP maintenance in pregnancy and the mechanism of ENaC activation in pregnancy is via the MR. (Support: NIH K22 award and CHRB award)