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Increased serum angiotensin-converting enzyme activity and plasma angiotensin II levels during pregnancy and postpartum in the diabetic rat

Institute of Hypertension and Kidney Diseases

Geoffrey Boner

Institute of Hypertension and Kidney Diseases

Shaul Giler

Experimental Surgery Unit, Rabin Medical Center (Campus Beilinson) and Felsenstein Research Center, Petah Tikva and Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel

Arie Erman

Institute of Hypertension and Kidney Diseases, aerman@ clalit.org.il

Objective The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, electrolyte balance and renal function in normal human pregnancy. The present study was designed to assess various components of the RAS and renal function during pregnancy and immediately after pregnancy in the streptozotocin (STZ)-diabetic rat.

Methods Pregnant Wistar rats were allocated to three groups: I- control, non-diabetic rats (n=24), II- STZ-diabetic rats (STZ 55 mg/kg body weight, i.v. on day 10 of pregnancy, n=24), III- diabetic rats, as above, treated with insulin (4 units/day, s.c. n=21). On days 17—18 of pregnancy, or within 24 hours after delivery, the rats were sacrificed and the various components of the RAS were determined.

Results Urinary protein excretion (UP) and creatinine clearance (CCr) were greater in group II, four days after STZ, than in group I (UP: I-7.6±2.8, II-18.6±6.3 mg/24-hour, p<0.001, CCr: I-1.04±0.33, II-2.38±0.7 ml/minute, p<0.001). Mean (±SD) serum angiotensin-converting enzyme (ACE) activity and plasma angiotensin II (Ang II) levels at days 17—18 of pregnancy were greater in the untreated diabetic rats than in control pregnant rats (ACE: 163±18 vs . 111±21 nmol/ml/minute, p<0.001, Ang II: 115±45 vs. 43±10 pg/ml, p<0.005). Postpartum serum ACE activity and plasma Ang II levels were greater in group II (ACE: I-123±14, II-142±24, III-108±21 nmol/ml/minute, p<0.01, Ang II: I-56±38, II-148±62, III-38±17 pg/ml, p<0.001). ACE activity in the lung was greater, whereas the activity in the renal cortex was less, in group II than in group I. Kidney weight in untreated diabetic rats was greater than in the other two groups.

Conclusion Increased serum ACE activity during pregnancy and postpartum in the untreated diabetic rat is associated with enhanced serum Ang II levels, which may contribute to increased protein excretion and renal hypertrophy.

Key Words: angiotensin-converting enzyme • kininase II • angiotensin • diabetes mellitus • insulin • pregnancy

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 3, 193-198 (2001)
DOI: 10.3317/jraas.2001.027


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