Abstract 548: Reduced Urinary Angiotensinogen Excretion in Preeclampsia

Abstract

Objective: Preeclampsia (preE) is a hypertensive disorder of pregnancy. We reported the suppression of circulatory renin-angiotensin system (RAS) in a rat model of preE. Urinary angiotensinogen has been considered as an indicator of intrarenal angiotensin status in hypertension. Little is known about the urinary angiotensinogen in preE. This study evaluates the level of urinary excretion of angiotensinogen in preE to assess the RAS status. Methods: Normal pregnant (n=57) and preE (n=32) patients were recruited from Scott & White Hospital and had their blood drawn between 21 to 40 weeks of pregnancy. Criteria for diagnosis of preE included blood pressure >140/90 mm Hg and proteinuria >300 mg of protein/24h. Two groups of rats were used: normal pregnant (n=10) and preE rats (n=10) which were given weekly injections of desoxycorticosterone acetate and 0.9% saline to drink. Urinary angiotensinogen levels and the plasma AngII levels were assayed by ELISA. The kidney expression of (pro)renin receptor, AT 1 receptor, AT 2 receptor, and renin for the two groups of rats was measured by western blot. Results are expressed as means with SD and comparisons made using Student’s t test with p<0.05 considered significant. Results: In preE patients, the mean urinary excretion of angiotensinogen (2.0 ± 1.1 ng/mg creatinine) differed (p<0.05) from that in patients with normal pregnancy (2.7 ± 1.5 ng/mg creatinine). The urinary excretion of angiotensinogen (PreE: 1.5 ± 0.3, NP: 2. 3 ± 0.4 nmol/day) also differed (p<0.05) in preE rats compared to NP. The plasma concentration of Ang II for preE rats (25 ± 3 fmol/ml) differed (p<0.05) compared to NP rats (39 ± 5 fmol/ml). The kidney expression of (pro)renin receptor was downregulated (p=0.008), while the AT 1 receptor was upregulated (p=0.01) in preE rats compared to NP. However, the kidney expression of AT 2 receptor (1.0 vs 1.1) and renin (1.0 vs 1.4) were similar in NP and PDS rats (p=0.63 and p=0.12, respectively). Conclusions: We demonstrated that urinary excretion of angiotensinogen is reduced in both patients with preE and in a rat model of preE. The kidney expression of RAS components was either downregulated or remained unchanged in preE rats. This finding indicates that preE is an Ang-II independent form of systemic hypertension.