Chronic vasodilation produces plasma volume expansion and hemodilution in rats: consequences of decreased effective arterial blood volume

Abstract

Fekete A, Sasser JM, Baylis C. Chronic vasodilation produces plasma volume expansion and hemodilution in rats: consequences of decreased effective arterial blood volume. Am J Physiol Renal Physiol 300: F113-F118, 2011. First published October 27, 2010 doi:10.1152/ajprenal.00478.2010 expansion is required for optimal pregnancy outcomes; however, the mechanisms responsible for sodium and water retention in pregnancy remain undefined. This study was designed to test the "arterial underfill hypothesis" of pregnancy which proposes that an enlarged vascular compartment (due to systemic vasodilation and shunting of blood to the placenta) results in renal sodium and water retention and PV expansion. We produced chronic vasodilation by 14 days administration of nifedipine (NIF; 10 mg·kg Ϫ1 ·day Ϫ1 ) or sodium nitrite (NaNO2; 70 mg·kg Ϫ1 ·day Ϫ1 ) to normal, nonpregnant female Sprague-Dawley rats. Mean arterial pressure, monitored by telemetry, was reduced by both NIF and NaNO2 but was unchanged in control rats. At day 14, vasodilator treatment lowered hematocrit and increased PV (determined by Evans blue dye dilution). Plasma osmolarity (Posm), sodium (PNa), and total protein concentrations all fell. These responses resemble the responses to normal pregnancy with hemodilution, marked PV expansion, and decreased P osm and PNa. Our previous work indicates a role of increased inner medullary phosphodiesterase-5 (PDE5) in the sodium retention of pregnancy. Here, we found that inner medullary PDE5A mRNA and protein expression were increased by both NIF and NaNO2 treatment vs. control; however, neither renal cortical nor aortic PDE5 expression was changed by vasodilator treatment. We suggest that a primary, persistent vasodilation drives increased inner medullary PDE5 expression which facilitates continual renal Na retention causing "refilling" of the vasculature and volume expansion. nifedipine; sodium nitrite; phosphodiesterase-5; sodium balance NORMAL PREGNANT WOMEN UNDERGO a progressive plasma volume expansion which begins in the first trimester, peaks near gestational week 32, and remains elevated until term (5,12,25). The demands of fetal development require this increased circulating volume, and suboptimal plasma volume expansion is associated with complications of pregnancy and "small for gestational age" (SGA) babies (6). Plasma volume expansion also occurs during pregnancy in the rat and is the result of net renal sodium and fluid retention (2). In the rat, metabolic cage studies demonstrated a positive sodium balance predominately during late pregnancy (7). Furthermore, inhibition of volume expansion by restricting sodium intake in the rat compromises pregnancy close to term (24).The mechanism of sodium and water retention in pregnancy remains a mystery. One hypothesis to explain this phenomenon suggests that pregnancy is an "underfill" state (30). During pregnancy, there is an early systemic vasodilation that is combined with later placental arteriovenous shunting resulting in an enlarged vascular compartment. Acc...

Chronic vasodilation increases renal medullary PDE5A and α-ENaC through independent renin-angiotensin-aldosterone system pathways

“…NIF increased PDE5A protein abundance in the renal IM (as reported previously) (10), and this increase persisted when SPR was also administered. No changes were observed in PDE5A protein abundance in the OM or CTX of NIF or NIF ϩ SPR-treated animals ( Fig.…”

“…*P Ͻ 0.05 vs. CON. the vasculature, as well as increased PDE5A protein abundance in medulla (10). The similarity in medullary responses to these two structurally and mechanistically diverse vasodilators suggests that it is vasodilation "per se" that initiates these renal changes.…”

“…The line was then flushed with 200 l of isotonic saline. Arterial blood collections (300 l) were taken at 5 and 10 min after dye infusion and used to calculate PV as described previously (10). At the end of the experiment, the kidneys were removed, separated into cortex (CTX), outer medulla (OM), and inner medulla (IM), snap-frozen in liquid nitrogen, and stored at Ϫ80°C.…”

“…Chronic (14-day) systemic vasodilation with the calcium channel blocker nifedipine (NIF) and the NO donor NaNO 2 produced PVE and hemodilution and increased medullary PDE5A (10). One aim of the present study was to analyze the response of the distal nephron apical sodium transporters, ␣-ENaC in particular, during chronic systemic vasodilation.…”

Salt-sensitive (Rapp) rats from Envigo spontaneously develop accelerated hypertension independent of ovariectomy on a low-sodium diet

“…In 4-mo-old rats, radio transmitters (no. HD-S10; Data Sciences International; St. Paul, MN) were implanted in the left femoral artery, as we previously described (12). Carprofen was administered subcutaneously for up to 2 days postsurgery.…”