Renal interstitial hydrostatic pressure and natriuretic responses to volume expansion in pregnant rats

2002 ◽  
Vol 282 (5) ◽  
pp. F821-F825 ◽  
Author(s):  
Ali A. Khraibi ◽  
Michael J. Solhaug ◽  
Anca D. Dobrian ◽  
Theresa J. Berndt
Keyword(s):  
Hydrostatic Pressure ◽  
Plasma Volume ◽  
Volume Expansion ◽  
Maximum Level ◽  
Fractional Excretion ◽  
Normal Pregnancy ◽  
Sprague Dawley ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Fractional Excretion Of Sodium

During normal pregnancy, a gradual plasma volume expansion (VE) occurs and reaches a maximum level at late term. Pressure natriuresis and renal interstitial hydrostatic pressure (RIHP) responses are attenuated in pregnant rats. Also, basal RIHP is lower in pregnant rats, suggesting an increase in renal interstitial compliance during pregnancy. This adaptation may contribute to the increase in plasma volume that is required for a normal pregnancy, because increases in RIHP have been consistently shown to produce natriuresis and diuresis. Acute saline VE (5% body wt/30 min) has been shown to increase RIHP in normal nonpregnant rats. Therefore, the objective of this study was to determine RIHP, natriuretic, and diuretic responses to VE in nonpregnant ( n = 7), midterm pregnant ( n = 8), and late-term pregnant ( n = 8) Sprague-Dawley rats. Although VE significantly increased RIHP, fractional excretion of sodium (FENa), and urine flow rate (V˙) in all groups, ΔRIHP was highest for nonpregnant (3.0 ± 0.3 mmHg) compared with midterm pregnant (1.6 ± 0.1 mmHg; P < 0.05 vs. nonpregnant) and late-term pregnant rats (1.2 ± 0.1 mmHg; P < 0.05 vs. both midterm pregnant and nonpregnant rats). ΔFENa and ΔV˙ were similar in all groups: 5.8 ± 1.0% and 231 ± 27 μl/min for nonpregnant, 6.8 ± 1.3% and 173 ± 16 μl/min for midterm pregnant, and 7.6 ± 1.2% and 203 ± 10 μl/min for late-term pregnant rats, respectively. In conclusion, basal RIHP and the increase in RIHP during VE were attenuated during pregnancy; however, the natriuretic and diuretic responses to VE remain intact during the course of pregnancy.

Renal interstitial hydrostatic pressure and pressure natriuresis in pregnant rats

2000 ◽  
Vol 279 (2) ◽  
pp. F353-F357 ◽  
Author(s):  
Ali A. Khraibi
Keyword(s):  
Hydrostatic Pressure ◽  
Perfusion Pressure ◽  
Fractional Excretion ◽  
Normal Pregnancy ◽  
Renal Perfusion ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Fractional Excretion Of Sodium ◽  
Pressure Natriuresis

The objective of this study was to test the hypothesis that a decrease in renal interstitial hydrostatic pressure (RIHP) accounts for the blunted pressure natriuresis during pregnancy. RIHP was measured in nonpregnant (NP; n = 9), midterm pregnant (MP; 12–14 days after conception; n = 10), and late-term pregnant (LP; 18–21 days after conception; n = 12) female Sprague-Dawley rats at two renal perfusion pressure (RPP) levels (99 and 120 mmHg). At the lower RPP level, RIHP was 5.9 ± 0.3 mmHg for NP, 3.4 ± 0.4 mmHg for MP ( P < 0.05 vs. NP), and 2.9 ± 0.1 mmHg for LP ( P < 0.05 vs. NP) rats. The increase in RPP from 99 to 120 mmHg resulted in pressure natriuretic and diuretic responses in all groups; however, the increases in fractional excretion of sodium (ΔFENa), urine flow rate (ΔV), and ΔRIHP were significantly greater ( P < 0.05) in NP compared with both MP and LP rats. ΔFENa, ΔV, and ΔRIHP were 2.06 ± 0.28%, 81.44 ± 14.10 μl/min, and 3.0 ± 0.5 mmHg for NP; 0.67 ± 0.13%, 28.03 ± 5.28 μl/min, and 0.5 ± 0.2 mmHg for MP; and 0.48 ± 0.12%, 18.14 ± 4.70 μl/min, and 0.4 ± 0.1 mmHg for LP rats. In conclusion, RIHP is significantly lower in pregnant compared with nonpregnant rats at similar RPP levels. Also, the ability of pregnant rats to increase RIHP in response to an increase in RPP is blunted. These changes in RIHP may play an important role in the blunted pressure natriuresis and contribute to the conservation of sodium and water that is critical for fetal growth and development during normal pregnancy.

Role of nitric oxide in the natriuretic and diuretic responses in pregnant rats

2003 ◽  
Vol 285 (5) ◽  
pp. F938-F944 ◽  
Author(s):  
Ali A. Khraibi ◽  
Tianzheng Yu ◽  
Daiyi Tang
Keyword(s):  
Nitric Oxide ◽  
Control Period ◽  
Fractional Excretion ◽  
Normal Pregnancy ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sd Rats ◽  
Fractional Excretion Of Sodium ◽  
Lower Ability

Normal pregnancy is characterized by sodium conservation and increase in plasma volume, yet the natriuretic response to acute saline volume expansion (VE) is intact in pregnant rats. Nitric oxide (NO) has been suggested to play a role in renal and cardiovascular adaptations to normal pregnancy. The objective of this study was to determine the role of NO in the natriuretic and diuretic responses to VE during pregnancy. Infusion of NG-monomethyl-l-arginine (l-NMMA) was used to inhibit NO synthesis. Nine groups of Sprague-Dawley (SD) rats were studied: nonpregnant (NP-VE, n = 7), midterm pregnant (MP-VE, n = 8), and late-term pregnant (LP-VE, n = 7) SD groups that underwent VE alone after a control period; NP-l-NMMA ( n = 7), MP-l-NMMA ( n = 8), and LP-l-NMMA ( n = 7) SD groups that were infused with l-NMMA after a control period; and another three groups of SD rats (NP-VE-l-NMMA, n = 8; MP-VE-l-NMMA, n = 7; and LP-VE-l-NMMA, n = 12) that underwent simultaneous VE and l-NMMA infusion after a control period. The change in fractional excretion of sodium was 7.22 ± 1.03% for NPVE, 9.89 ± 1.85% for NP-l-NMMA, and 17.66 ± 1.85% for NP-VE-l-NMMA ( P < 0.05 vs. NP-VE and NP-l-NMMA); 6.61 ± 1.07% for MP-VE, 7.99 ± 1.92% for MP-l-NMMA, and 10.24 ± 1.91% for MP-VE-l-NMMA [not significant (NS) vs. MP-VE and MP-l-NMMA]; 8.20 ± 1.92% for LP-VE, 8.09 ± 0.70% for LP-l-NMMA, and 7.57 ± 1.11% for LP-VE-l-NMMA (both NS vs. LP-VE and LP-l-NMMA). The increase in renal interstitial hydrostatic pressure was significantly greater in all NP compared with pregnant groups with similar experimental intervention (i.e., VE, l-NMMA, or VE-l-NMMA). In conclusion, the natriuretic and diuretic responses to VE and l-NMMA infusion were additive in NP but not in pregnant rats, indicating a possible lower ability of pregnant rats to respond to combined significant natriuretic and diuretic stimuli.

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

2011 ◽  
Vol 300 (1) ◽  
pp. F113-F118 ◽  
Author(s):  
Andrea Fekete ◽  
Jennifer M. Sasser ◽  
Chris Baylis
Keyword(s):  
Plasma Volume ◽  
Volume Expansion ◽  
Water Retention ◽  
Normal Pregnancy ◽  
Blue Dye ◽  
Sprague Dawley ◽  
Plasma Volume Expansion ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Vasodilator Treatment

Plasma volume (PV) 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−1·day−1) or sodium nitrite (NaNO2; 70 mg·kg−1·day−1) 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 Posm 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.

scholarly journals Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to ANP in the pregnant rat

2007 ◽  
Vol 292 (2) ◽  
pp. F655-F659 ◽  
Author(s):  
Sarah Knight ◽  
Harold Snellen ◽  
Michael Humphreys ◽  
Chris Baylis
Keyword(s):  
Volume Expansion ◽  
Fractional Excretion ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Contralateral Kidney ◽  
Fractional Excretion Of Sodium ◽  
Normal Rat ◽  
Renal Clearances ◽  
Natriuretic Effect

Normal rat pregnancy is characterized by plasma volume expansion due to renal sodium retention and is associated with a blunted response to natriuretic stimuli, such as atrial natriuretic peptide (ANP). ANP signals via cGMP, and phosphodiesterases (PDE) inactivate cGMP and terminate the natriuretic response. We previously reported that increased medullary PDE-5 activity occurs in rat pregnancy, which may be the mechanism of the blunted natriuretic effect of ANP. Here, we used anesthetized 16-day pregnant and virgin rats to investigate whether intrarenal infusion of a selective PDE-5 inhibitor, sildenafil, would reverse the blunted response to ANP in pregnancy. We measured blood pressure, renal clearances using inulin and p-aminohippuric acid, and electrolyte excretion at baseline and during an ANP infusion. ANP caused a fall in mean arterial pressure in all groups, and sildenafil induced a further reduction. We observed an increase in sodium excretion with ANP in all rats, but this was blunted in the vehicle-infused pregnant rats. This could not be explained by differences in renal hemodynamics and was of tubular origin, as reflected by the reduced rise in fractional excretion of sodium with ANP in the pregnant rat given vehicle (45 ± 11 vs. 204 ± 49%; P < 0.05). However, intrarenal sildenafil increased the natriuretic response and the rise in fractional excretion of sodium to the virgin value (226 ± 23 vs. 245 ± 73%; not significant), whereas the blunting persisted in the contralateral kidney. This demonstrates that increased intrarenal PDE-5 mediates the blunted natriuretic response to ANP during pregnancy and may contribute to the physiological volume expansion.

scholarly journals The natriuretic and diuretic response to dopamine is maintained during rat pregnancy

2008 ◽  
Vol 294 (6) ◽  
pp. F1342-F1344 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Chris Baylis
Keyword(s):  
Blood Pressure ◽  
Collecting Duct ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Fractional Excretion ◽  
Sprague Dawley ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Dopamine Infusion ◽  
Fractional Excretion Of Sodium

During pregnancy, there is a marked plasma volume expansion due to renal sodium retention. Pregnant rats exhibit a blunted response to natriuretic stimuli that signal via cGMP, and expression and activity of the cGMP phosphodiesterase PDE-5 are upregulated in the inner medullary collecting duct during pregnancy. Here, we tested the hypothesis that the natriuretic response to a cAMP agonist, dopamine, is maintained during pregnancy. Anesthetized pregnant ( day 16) and age-matched virgin Sprague-Dawley rats were used to determine whether dopamine-cAMP-mediated natriuresis remains intact in pregnant rats. Blood pressure, renal clearances of inulin and p-aminohippuric acid, and excretion of sodium were measured during baseline and dopamine infusion periods. Pregnant rats had a lower blood pressure and hematocrit at baseline than their age-matched virgin counterparts. Dopamine infusion decreased blood pressure and increased glomerular filtration rate and renal plasma flow in virgin but not pregnant rats. Dopamine infusion also increased urine volume, sodium excretion, and the fractional excretion of sodium to a similar extent in virgin and pregnant rats. These results indicate that a cAMP-mediated natriuresis and diuresis (stimulated by dopamine) persists in pregnant rats.

Role of renal interstitial hydrostatic pressure in natriuresis of systemic nitric oxide inhibition

1993 ◽  
Vol 264 (3) ◽  
pp. F411-F414 ◽  
Author(s):  
J. A. Haas ◽  
A. A. Khraibi ◽  
M. A. Perrella ◽  
F. G. Knox
Keyword(s):  
Nitric Oxide ◽  
Hydrostatic Pressure ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Renal Perfusion ◽  
Significant Rise ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Suprarenal Aorta ◽  
Fractional Excretion Of Sodium

Systemic inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) increases renal perfusion pressure (RPP) and urinary sodium excretion. Increased RPP has been proposed as one of the mechanisms for the natriuresis caused by intravenous infusion of L-NMMA. We tested the hypothesis that increases in renal interstitial hydrostatic pressure (RIHP) are required for the natriuresis of L-NMMA infusion. Experiments were performed in four groups of Sprague-Dawley rats in which partial aortic clamping and/or bilateral renal decapsulation was performed to control RPP and RIHP. Infusion of L-NMMA (15 mg/kg bolus + 500 micrograms.kg-1 x min-1 continuous infusion) increased RPP (delta+ 14 +/- 1 mmHg), RIHP (delta+ 3.6 +/- 0.7 mmHg), and fractional excretion of sodium (FENa; delta 2.4 +/- 0.6%, P < 0.005). When RPP was prevented from increasing by controlling RPP with an adjustable clamp around the suprarenal aorta, RIHP and FENa did not significantly change. When only RIHP was held constant by bilateral renal decapsulation, FENa was not significantly increased (delta+ 0.68 +/- 0.36%, not significant), despite a significant rise in RPP (delta+ 18 +/- 2 mmHg, P < 0.001). Control of both RPP and RIHP prevented the increase in FENa. Thus, when renal interstitial pressure was controlled, the infusion of L-NMMA did not result in an increase in FENa. These results demonstrate that an increase in RIHP is a necessary component in the natriuresis due to systemic infusion of L-NMMA.

ANF secretion and renal responses to volume expansion with equilibrated blood

1988 ◽  
Vol 255 (5) ◽  
pp. F936-F943 ◽  
Author(s):  
R. V. Paul ◽  
T. Ferguson ◽  
L. G. Navar
Keyword(s):  
Blood Volume ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Fractional Excretion ◽  
High Dose ◽  
Sprague Dawley ◽  
Blood Volume Expansion ◽  
Step Procedure ◽  
Sprague Dawley Rats ◽  
Fractional Excretion Of Sodium

To evaluate the role of atrial natriuretic factor (ANF) in the renal response to acute blood volume expansion without hemodilution, a reservoir syringe filled with donor rat blood was connected to the femoral artery and vein of anesthetized Sprague-Dawley rats to allow rapid equilibration of the reservoir with the intravascular blood. Volume expansion with blood from the reservoir in two steps (of 1 and 1.5% body wt, separated by 1 h, n = 5 rats) produced a mean peak increase in plasma immunoreactive ANF from 99 +/- 21 to 1,310 +/- 230 pg/ml (P less than 0.001); plasma ANF levels throughout these experiments correlated significantly with simultaneously measured urine flow (r = 0.74, P less than 0.005) and sodium excretion (r = 0.65, P less than 0.005). Another group (n = 7) underwent the same two-step procedure; after the second volume expansion, high-dose atriopeptin III infusion (0.4 microgram.kg-1.min-1 did not further increase fractional excretion of sodium (3.17 +/- 0.27 to 2.50 + 0.39%, P = NS). In another group (n = 9 rats), the same dose of atriopeptin III was started before any blood volume expansion. After the resulting hypotension was corrected by restoration of blood volume, an additional 1.5% body weight blood volume expansion did not further augment sodium excretion. We conclude that the diuresis and natriuresis, which occur in response to volume expansion without hemodilution, rise and fall in parallel with immunoreactive ANF in the plasma, and that ANF and acute blood volume expansion act on the kidney through a similar, saturable mechanism.

scholarly journals Increased renal α-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy

2010 ◽  
Vol 299 (5) ◽  
pp. R1326-R1332 ◽  
Author(s):  
Crystal West ◽  
Zheng Zhang ◽  
Geoffrey Ecker ◽  
Shyama M. E. Masilamani
Keyword(s):  
Plasma Volume ◽  
Late Pregnancy ◽  
Normal Pregnancy ◽  
In Vivo Studies ◽  
Volume Status ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Mineralocorticoid Receptor Antagonist ◽  
The Difference

Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na+/H+ exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy ( days 18–20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (UNaV postbenzamil-UNaV postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

Effects of insulin on renal interstitial hydrostatic pressure and natriuretic response to volume expansion in diabetic rats

2004 ◽  
Vol 286 (4) ◽  
pp. R751-R755 ◽  
Author(s):  
Daiyi Tang ◽  
Tianzheng Yu ◽  
Ali A. Khraibi
Keyword(s):  
Hydrostatic Pressure ◽  
Volume Expansion ◽  
Insulin Treatment ◽  
Critical Role ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Water Excretion ◽  
Fractional Excretion Of Sodium

Diabetes mellitus (DM) is characterized by alterations in fluid balance and blood volume homeostasis. Renal interstitial hydrostatic pressure (RIHP) has been shown to play a critical role in mediating sodium and water excretion under various conditions. The objective of this study was to determine the effects of immediate and delayed initiation of insulin treatment on the restoration of the relationship between RIHP, natriuretic, and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body wt). Four groups of female Sprague-Dawley rats were studied: normal control group (C), untreated diabetic group (D), immediate insulin-treated diabetic group (DI; treatment with insulin for 2 wk was initiated immediately when diabetes was confirmed, which was 2 days after STZ injection), and delayed insulin-treated diabetic group (DDI; treatment with insulin for 2 wk was initiated 2 wk after STZ injection). RIHP and sodium and water excretions were measured before and during VE (5% body wt/30 min) in the four groups of anesthetized rats. VE significantly increased RIHP, fractional excretion of sodium (FENa), and urine flow rate (V) in all groups of rats. Basal RIHP, RIHP response to VE (ΔRIHP), and FENa and V responses to VE (ΔFENa and ΔV) were significantly lower in the D group compared with the C group of rats. ΔRIHP was significantly higher in both DI and DDI groups compared with D group but was similar to that of the C group of rats. While in the DI group the ΔFENa response to VE was restored, ΔFENa was significantly increased in DDI compared with D group, but it remained lower than that of the C group. In conclusion, insulin treatment initiated immediately after the onset of diabetes restores basal RIHP and RIHP, natriuretic, and diuretic responses to VE; however, delayed insulin treatment restores the basal RIHP and RIHP response to VE but does not fully restore the natriuretic response to VE.

scholarly journals Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat

2010 ◽  
Vol 299 (4) ◽  
pp. F810-F814 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Xi-Ping Ni ◽  
Michael H. Humphreys ◽  
Chris Baylis
Keyword(s):  
Nitric Oxide ◽  
Volume Expansion ◽  
Collecting Duct ◽  
Pde5 Inhibitor ◽  
Nitric Oxide Donor ◽  
Plasma Volume Expansion ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Fractional Excretion Of Sodium ◽  
Phosphodiesterase 5

Pregnancy is characterized by plasma volume expansion and renal sodium retention with loss of natriuretic response to atrial natriuretic peptide due to increased medullary phosphodiesterase-5 (PDE5). Here, we determined whether natriuretic responses to nitric oxide (NO) are also blunted in pregnancy due to increased PDE5. Anesthetized 16-day pregnant and virgin rats were studied at baseline and during intrarenal infusion of the NO donor spermine NONOate (2.5 nmol/min), the PDE5 inhibitor sildenafil (SILD; 0.5 μg/min), or a combination. The right (noninfused) kidney served as a control. Intrarenal NONOate had no effect on mean arterial pressure (MAP); however, SILD reduced MAP in virgin rats, and the combination of NONOate+SILD reduced MAP in both virgin and pregnant rats. Neither NONOate nor SILD altered glomerular filtration rate. NONOate and SILD each stimulated sodium excretion (UNaV) and fractional excretion of sodium (FENa) in virgin rats, but the combination did not result in an additional natriuretic response. However, NONOate infusion did not increase UNaV or FENa in pregnant rats, but the natriuretic response to NONOate was restored with SILD, and SILD alone produced a natriuresis during pregnancy. Sodium nitroprusside (10−4 mol/l)-stimulated cGMP accumulation from inner medullary collecting duct cells was blunted in cells from pregnant vs. virgin or postpartum rats and was restored by treatment with the PDE5 inhibitor DMPPO (10−7 mol/l). Therefore, increased intrarenal PDE5 mediates the blunted natriuretic response to NO, and loss of responsiveness to the cGMP-dependent, natriuretic agents may contribute to volume expansion during pregnancy.

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