Abstract-To test the hypothesis that normal volume expansion during pregnancy is impaired during chronic renal failure, we evaluated the effects of 5/6 nephrectomy (Nx) in Sprague-Dawley rats. Partial Nx was produced by ligation of 2/3 renal arteries and contralateral Nx. Control rats had a sham operation. Four weeks later, rats were assigned to nonpregnant (nϭ6/each) or pregnant groups (nϭ11 to 12/each). At day 21, blood pressure, plasma volume, renal function, hormonal levels, and reproductive outcome were determined. Statistical analysis was performed by ANOVA, and values were expressed as meanϮSEM. Rats with 5/6 Nx had proteinuria and lower creatinine clearance; pregnancy did not affect these parameters. Blood pressure increased in 5/6 Nx rats and was reduced by pregnancy. Key Words: pregnancy Ⅲ kidney failure Ⅲ plasma volume Ⅲ renin Ⅲ kallikrein Ⅲ aldosterone N ormal pregnancy is characterized by an initial reduction in peripheral vascular resistance that leads to several consequences such as decreased blood pressure, higher cardiac output, stimulation of the renin-angiotensin-aldosterone axis, and renal sodium and water retention, with expansion of plasma volume. 1-4 These changes allow an adequate supply of blood to the placenta and the developing fetus, and their absence is associated with pregnancy complications such as preeclampsia and fetal growth restriction. 5,6 To achieve positive sodium balance and cumulative plasma volume expansion, important changes in renal function also occur during pregnancy. There is a rise in glomerular filtration rate (GFR) and in renal plasma flow, the pressure natriuretic response is markedly blunted, 7,8 and vasoactive hormones from renal origin, such as kallikrein and renin, are increased during pregnancy. 9 On the basis of these observations, we have speculated that normal renal function and the ability of the kidney to increase the production of vasoactive hormones are important for adequate plasma volume expansion during pregnancy. To test this hypothesis, in the present study we evaluated the maternal and fetal effects of 5/6 nephrectomy (5/6 Nx) in SpragueDawley rats. In addition to the abnormalities characteristic of chronic renal failure, such as decreased GFR, moderate hypertension, and glomerular disease, 10 5/6 Nx is associated with alterations in the renin-angiotensin-aldosterone and kallikrein-kinin systems. 11-13
Methods
Experimental DesignFemale Sprague-Dawley rats (160 to 190 g initial weight) were maintained at the Center for Medical Research animal care facilities in a controlled environment (22°to 24°C and a 12-hour light/dark cycle). The protocols met international guidelines for animal welfare and were reviewed and approved by the Institutional Review Board of the School of Medicine.Partial Nx was accomplished by means of a 2-stage operation, as previously described. 10 Two of three branches of the left renal artery were ligated to produce renal infarction, and contralateral nephrectomy was done 1 week later. Control animals had a sham operation. Fo...