The acute pressure natriuresis response blunted and the blood pressure response reset in the normal pregnant rat

doi:10.1016/S0002-9378(98)70384-9

American Journal of Obstetrics and Gynecology

Volume 179, Issue 2, August 1998, Pages 486-491

https://doi.org/10.1016/S0002-9378(98)70384-9 Get rights and content

Abstract

OBJECTIVES: Our purpose was to test the hypothesis that the acute pressure natriuresis curve was reset in pregnancy to facilitate the volume expansion.

STUDY DESIGN: Studies were done with 14- to 16-day pregnant (n = 8) and age-matched virgin female (n = 6) Sprague-Dawley rats that were under general anesthesia. The left kidney was denervated, and mechanical clamps were placed on the aorta above and below the renal arteries for manipulation of renal perfusion pressure. Rats received intravenous 0.9% sodium chloride (1.5% body weight/h) and a cocktail of vasoactive factors to suppress variation in endogenous hormones. Renal perfusion pressure was varied acutely from 125 to 95 mm Hg, and glomerular filtration rate, renal plasma flow, sodium excretion, and urine flow were measured in both kidneys at each renal perfusion pressure. Data were analyzed by unpaired t test and by homogeneity by slopes.

RESULTS: The acute pressure natriuresis curve was blunted in pregnant rats versus virgins, and the renal nerves were not responsible. The blunted natriuretic response in pregnancy was due to loss of tubular epithelial responsiveness to increased blood pressure.

CONCLUSION: The pressure natriuretic response is markedly blunted in pregnancy, permitting the cumulative plasma volume expansion to occur. Contrary to nongravid states, blunting of the acute pressure natriuresis curve in pregnancy is not associated with increased blood pressure because of the profound peripheral vasodilation. This suggests an alteration in the mechanism(s) normally linking blood pressure control to the acute pressure natriuresis relationship. (Am J Obstet Gynecol 1998;179:486-91.)

Section snippets

Methods

Experiments were conducted on 14 female Sprague-Dawley rats (3 to 5 months old) from Harlan Sprague Dawley, Inc, Indianapolis. Rats were maintained on standard rat food (~24% protein, ~1% sodium chloride) and free access to drinking water. Day 1 of pregnancy was determined by the presence of sperm in vaginal smears. Pressure-natriuresis experiments were conducted at 14 to 16 days of pregnancy (n = 8) and in age-matched virgins (n = 6).

We used an adaptation of the experimental model developed by

Results

Pregnant rats were heavier (284 ± 7 g) than virgins (250 ± 2 g; P < .005). Plasma volume expansion was indicated by a decline in hematocrit at days 14 to 16 of pregnancy (44 ± 1 vs 47 ± 1 vol%; P < .01 vs virgins). The usual gestational rise in glomerular filtration rate and renal plasma flow was not seen, probably because of the infusion of vasoactive hormones (Table I).

The relationship between urinary sodium excretion and renal perfusion pressure in innervated and denervated kidneys of

Comment

In this study we have described the acute pressure-natriuresis relationship in the pregnant rat. We had hypothesized that the cumulative sodium retention and plasma volume expansion of pregnancy could not coexist with a normally operating acute pressure natriuresis. Our study confirms this hypothesis because we found a marked decrease in the gain of the relationship between urinary sodium excretion and renal perfusion pressure in the pregnant rat. This suggests a diminished natriuretic response

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Cited by (24)

Normal and Abnormal Volume Homeostasis
2009, Chesley's Hypertensive Disorders in Pregnancy
This chapter describes changes in volume, renin–angiotensin–aldosterone, and other mineralocorticoids in abnormal pregnancies such as preeclampsia. Pregnancy is a physiologic process where repeated adjustments occur in the steady state marked by changes in both intracellular and extracellular volume. Each new steady state value is then held within relatively narrow limits, that is, these changes are sensed as normal and “defended” in face of variations in fluid and sodium intake. There is a 30–50% increase in extracellular fluid (ECF), plasma, and blood volume (associated with 30–50% increases in cardiac output, glomerular filtration rate (GFR) and renal blood flow. Women who develop preeclampsia seem to fall into two subgroups: those who experience an abnormal shift of ECF from the vascular to the extravascular compartment, and those with a total reduction of ECF volume. This dichotomy may possibly reflect different disturbances in the normal volume homeostatic mechanisms of pregnancy. Women with preeclampsia/eclampsia have significantly reduced plasma volumes. The degree of contraction appears to be an index of severity, and in this respect the greatest decreases have been reported in nulliparas with eclampsia, the convulsive phase of the disease associated with extreme severity.
Renal interstitial hydrostatic pressure and natriuretic response to high doses of angiotensin II in pregnant rats
2006, American Journal of Hypertension
Administration of high doses of angiotensin II (Ang II) results in natriuretic and diuretic responses that are mediated by increases in renal perfusion pressure (RPP). Elevations in renal interstitial hydrostatic pressure (RIHP) caused by increases in mean arterial pressure (MAP) or RPP are associated with significant increases in urinary sodium excretion (U_NaV) and urine flow rate (V). In pregnant rats the renin-angiotensin system (RAS) is activated and basal RIHP is reduced. The exact relationship among MAP, RIHP, U_NaV, and V in response to a high pressor dose of Ang II during normal pregnancy is not known.
The objective of this study was to evaluate the relationship between MAP and RIHP, and determine the role of RIHP in the natriuretic and diuretic responses to administration of high dose of Ang II in midterm pregnant (MP) and nonpregnant (NP) Sprague-Dawley (SD) rats.
Intravenous infusion of Ang II (200 ng/kg/min) significantly increased MAP (ΔMAP), ΔU_NaV, and ΔV in anesthetized MP and NP rats. The ΔMAP, ΔU_NaV, and ΔV were 12 ± 2 mm Hg, 27.9 ± 2.7 μEq/min, and 197 ± 23 μL/min for MP rats and were similar (15 ± 3 mm Hg, 34.1 ± 4.3 μEq/min, and 242 ± 34 μL/min, respectively) for NP rats. The RIHP decreased significantly (P < .05) with Ang II infusion in NP (from 6.1 ± 0.2 to 3.9 ± 0.4 mm Hg) but not in MP (from 3.3 ± 0.3 to 4.1 ± 0.4 mm Hg) groups of rats. Acute renal decapsulation eliminated the change in RIHP mediated by high doses of Ang II infusion in the NP group, but did not affect MAP or the natriuretic and diuretic responses to Ang II in either the MP or NP groups of rats.
The natriuretic and diuretic responses to high doses of Ang II are not mediated by changes in RIHP in pregnant or nonpregnant rats.
Role of RIHP and renal tubular sodium transporters in volume retention of pregnant rats
2005, American Journal of Hypertension
Normal pregnancy is characterized by sodium and water conservation and an increase in plasma volume that is required for an uncomplicated pregnancy. Renal interstitial hydrostatic pressure (RIHP) is significantly decreased in pregnant rats. This decrease in RIHP may play an important role in the sodium and water retention that characterizes normal pregnancy. Paradoxically this enhanced renal sodium and water reabsorption appear to conflict with the consistent findings of a general decrease in abundance of renal tubular sodium transporters during normal pregnancy. The objective of this review is to examine the apparent discrepancy between the increases in renal tubular sodium and water reabsorption, facilitated by decreases in RIHP, and the seemingly discordant decreases in abundance of renal tubular transporters during normal pregnancy in rats.
Western blots and immunohistochemistry were used to evaluate abundance and localization of renal tubular transporters. RIHP was measured directly and continuously via a polyethylene (PE) matrix that was implanted in the left kidney of rats at the age of 11 to 16 weeks.
Average basal RIHP and fractional excretion of sodium (FE_Na) were found to be significantly lower (P < .05) in midterm pregnant (MP; n = 18) and late-term pregnant (LP; n = 20) rats compared with nonpregnant (NP; n = 16) rats (3.5 ± 0.3 mm Hg and 1.46 ± 0.24% for MP; 3.3 ± 0.1 mm Hg and 1.41 ± 0.21% for LP; and 7.6 ± 0.6 mm Hg and 3.67 ± 0.24% for NP). Cortical Na⁺-K⁺-ATPase and Na-Pi2a cotransporter (Na-Pi) protein expression tend to decline with pregnancy. Also cortical Na⁺-H⁺ exchanger–1 (NHE-1) protein expression declines steadily during the course of pregnancy from MP to LP compared with that in NP rats, and cortical Na⁺-H⁺ exchanger–3 (NHE-3) protein expression is significantly lower in MP and LP compared with NP rats.
We propose that during normal uncomplicated pregnancy, simultaneous decreases in RIHP and in net abundance of renal tubular sodium transporters occur. The effects of decreased RIHP exceed those of the reduction in net abundance, and presumably activity, of renal tubular transporters resulting in an enhanced net sodium and water retention during pregnancy.
Natriuretic response to direct renal interstitial volume expansion (DRIVE) in pregnant rats
2005, American Journal of Hypertension
Basal renal interstitial hydrostatic pressure (RIHP) is lower in pregnant rats, suggesting an increase in renal interstitial compliance during pregnancy. The RIHP responses to increases in renal perfusion pressure (RPP) and acute saline volume expansion (VE) are attenuated in pregnant rats. Pressure natriuresis and diuresis responses are significantly attenuated during normal pregnancy, whereas the natriuretic and diuretic responses to VE remain intact.
The objectives of this study were to use direct renal interstitial volume expansion (DRIVE) to selectively increase RIHP and determine the renal interstitial compliance and the relationship between RIHP, natriuretic, and diuretic responses in nonpregnant (NP; n = 8), midterm pregnant (MP; n = 8), and late-term pregnant (LP; n = 8) Sprague-Dawley (SD) rats.
DRIVE resulted in significant increases in RIHP, fractional excretion of sodium (FE_Na), and urine flow rate (V) in all groups of rats. The increase in RIHP (ΔIHP) was greatest for NP (3.3 ± 0.2 mm Hg) as compared to MP (1.3 ± 0.1 mm Hg; P < .05 v NP) and LP (1.4 ± 0.2 mm Hg; P < .05 v NP) in response to DRIVE showing that renal interstitial compliance was greater in MP and LP as compared to the NP group of rats. The increase in fractional excretion of sodium (ΔFE_Na) was similar in NP (3.1% ± 0.3%) and LP (3.6% ± 0.8%), but was significantly lower in MP (1.5% ± 0.4%; P < .05 v NP and LP) in response to DRIVE.
These data suggest that the blunted increase in RIHP and natriuresis in response to DRIVE in midterm pregnant rats may play an important role in the gradual plasma volume expansion that is occurring during this stage of pregnancy.
Mechanisms of altered renal sodium handling in age-related hypertension
2018, American Journal of Physiology - Renal Physiology
The enigma of continual plasma volume expansion in pregnancy: Critical role of the renin-angiotensin-aldosterone system
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^☆: From the Departments of Physiology and Statistics and Computer Science, West Virginia University.

^☆☆: Funded by National Institutes of Health grant No. HL 31933.

^★: Reprints not available from the authors.

^★★: 0002-9378/98 $5.00 + 0 6/1/89332

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The acute pressure natriuresis response blunted and the blood pressure response reset in the normal pregnant rat☆,☆☆,★,★★

Abstract

Section snippets

Methods

Results

Comment

Am J Obstet Gynecol

Kidney Int

The physiology of normal pregnancy. In Handbook of hypertension

Sodium balance during pregnancy in the rat

Am J Physiol

Renal physiology and disease in pregnancy

Body fluid volume regulation in health and disease: a unifying hypothesis

Ann Intern Med

Pregnant rats are refractory to the natriuretic actions of ANP

Am J Physiol

Urinary excretion of water, sodium and total solutes by the pregnant rat

Am J Physiol

Renal handling of acute sodium loads in pregnancy

Am J Physiol

The surprising kidney-fluid mechanism for pressure control: its infinite gain!

Hypertension

Characterization of a new model for the study of pressure-natriuresis in the rat

Am J Physiol