The enigma of continual plasma volume expansion in pregnancy: critical role of the renin-angiotensin-aldosterone system

Abstract

Pregnancy is characterized by avid renal sodium retention and plasma volume expansion in the presence of decreased blood pressure. Decreased maternal blood pressure is a consequence of reduced systemic vascular tone, which results from an increased production of vasodilators [nitric oxide (NO), prostaglandins, and relaxin] and decreased vascular responsiveness to the potent vasoconstrictor (angiotensin II). The kidneys participate in this vasodilatory response, resulting in marked increases in renal plasma flow and glomerular filtration rate (GFR) during pregnancy. In women, sodium retention drives plasma volume expansion (∼40%) and is necessary for perfusion of the growing uterus and fetus. For there to be avid sodium retention in the presence of the potent natriuretic influences of increased NO and elevated GFR, there must be modifications of the tubules to prevent salt wasting. The purpose of this review is to summarize these adaptations.

Keywords: ENaC; PDE5; RAAS; kidney; nitric oxide.

Fig. 1.

Curve fit and observed mean values for mean blood pressure (A) and plasma volume (B) values throughout pregnancy in controls and pregnancies complicated by fetal growth restriction (FGR) or preeclampsia (PE). [From Salas et al. (74) with permission.]

Fig. 2.

Cartoon showing time course of change in plasma volume (PV; ○) and blood pressure (BP; ■) during normal rat pregnancy, expressed as %change compared with the virgin (nonpregnant) value. Figure is compiled from data in Refs. , , , , based on studies in normal pregnant Munich Wistar and Sprague-Dawley rats.

Fig. 3.

Scheme showing proposed adaptations in the renin-angiotensin-aldosterone system (RAAS) and nitric oxide (NO)/atrial natriuretic peptide (ANP) systems, to permit both plasma volume expansion (PVE) and reductions in total peripheral vascular resistance (TPVR) during normal pregnancy.

Fig. 4.

Cartoon describing transporter changes in the aldosterone-sensitive distal nephron that occur in normal pregnancy in the rat. Figure is compiled from data in Refs., , , .

Fig. 5.

Change in sodium excretion (UNaV) expressed as %change from control (baseline) to experimental condition in virgin (V; open bars) and pregnant (P; solid bars) rats. Data were obtained from intravenous infusion of atrial natriuretic peptide (IV ANP) in the conscious rat (52) and anesthetized rat (42), endogenous (End) ANP released by an acute infusion of isotonic NaCl (63), pressure natriuresis (Press Nat) (53), and intrarenal (IR) infusion of the nitric oxide donor NONOate (79). *P < 0.05 in the natriuretic response between virgin and pregnant rats.

Fig. 6.

A: sodium nitroprusside (NaNP)-dependent cGMP accumulation by isolated inner medullary collecting duct (IMCD) cells from kidneys of virgin, pregnant, and postpartum rats. *P < 0.05 vs. virgin. B: the NaNP (10-4 mol/l) stimulated cGMP accumulation in cells from both virgin and pregnant rats in the presence of the PDE5 inhibitor DMPPO (10-7 mol/l). [Reproduced from Ref. .]

Fig. 7.

Mean change in blood pressure (BP; A) and change in plasma volume (PV; B) expressed as %change from control in virgin female rats after 14 days of nifedepine (NIF), angiotensin converting enzyme inhibitor (ACEI), NIF + angiotensin receptor type 1 antagonist losartan (LOS), and NIF + mineralocorticoid receptor antagonist spironolactone (SPR). *P < 0.05 in the change from control. Data were derived from Ref. .