|
Sign In to gain access to subscriptions and/or personal tools.
|
Increased serum angiotensin-converting enzyme activity and plasma angiotensin II levels during pregnancy and postpartum in the diabetic rat
David Jonathan van Dijk
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
References
- August P., Sealy JE The renin-angiotensin system in normal and hypertensive pregnancy and in ovarian function. In: Laragh JH and Brenner BM (eds.). Hypertension: Pathology, Diagnosis and Management. New York: Raven Press, 1990; 1761-78.
- Skinner S. The renin system in fertility and normal human pregnancy. In:Robertson JIS and Nicolls MG (eds.). The Renin-Angiotensin System. London: Gower Medical Publishing, 1993;1-16.
- Derkx FHM, Stuenk C., Schalekamp MPA, Visser W., Huisveld IH, Schalekamp Madh. Immunoreactive renin, prorenin, and enzymatically active renin in plasma during pregnancy and in women taking oral contraceptives J Clin Endocrinol Metabolism 1986;63:1008-15.[Abstract/Free Full Text]
- Reece EA, Coustan ER, Hayslett JP Diabetic nephropathy: pregnancy performance and fetomaternal outcome. Am J Obstet Gynecol 1988;59:56-66.
- van Dyk DJ, Erman A., Erman T., Chen-Gal B., Sulkes J., Boner G. Increased serum angiotensin converting enzyme activity in type I insulin dependent diabetes mellitus: Its relation to metabolic control and diabetic complications. Eur J Clin Invest 1994;24:463-7.[Web of Science][Medline]
[Order article via Infotrieve]
- Erman A., van Dyk DJ, Chen-Gal B. et al. Angiotensin converting enzyme activity in the serum, lung and kidney of diabetic rats. Eur J Clin Invest 1993;23:615-20.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Hod M., van Dijk DJ, Karp M. et al. Diabetic nephropathy and pregnancy: the effect of ACE inhibitors prior to pregnancy on fetomaternal outcome. Nephrol Dial Transplant 1995;10:2328-33.[Abstract/Free Full Text]
- Leehy DJ, SignhAK,Alavi N., Singh R. Role of angiotensin II in diabetic nephropathy. Kidney Int 2000; 58 (suppl 77): S93-S98.[CrossRef][Web of Science]
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ Protein measurement with the folin reagent. J Biol Chem 1951;193: 265-75.[Free Full Text]
- Bradford MM A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing of protein-dye binding. Anal Biochem 1976;72:248-54.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Chirstiansen T., Stodklide-Jorgensen H., Klebe JB, Flyvberg A. Changes in kidney volume during pregnancy in non-diabetic and diabetic rats measured by magnetic resonance imaging. Exp Nephrol 1998;6:302-6.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Valentovic MA, Elliott CW, Ball JBThe effect of streptozotocin-induced diabetes and insulin treatment on angiotensin converting enzyme activity. Res Comm Chem Pathol Pharmacol 1987; 58:27-38.[Web of Science][Medline]
[Order article via Infotrieve]
- Lieberman J., Sastre A. Serum angiotensin-converting enzyme: elevation in diabetes mellitus. Ann Int Med 1980; 93:825-6.[Abstract/Free Full Text]
- Parente JV, Frances JG, Greene LJ Angiotensin converting enzyme: serum levels during normal pregnancy. Am J Obstet Gynecol 1979;135:586-91.[Web of Science][Medline]
[Order article via Infotrieve]
- Dux S., Yaron A., Carmel A., Rosenfeld JB Renin, aldosterone, and serum-converting enzyme activity during normal and hypertensive pregnancy. Gynecol Obstet Invest 1984;17: 252-4.[Web of Science][Medline]
[Order article via Infotrieve]
- Brown L., Wall D., Marchant C., Sernia C. Tissue-specific changes in angiotensin II receptors in streptozotocin-diabetic rats. J Endocrinol 1997;154:355-62.[Abstract/Free Full Text]
- Erdos EG Angiotensin I converting enzyme and the changes in our concepts through the years. Hypertension 1990;16:363-70.[Abstract/Free Full Text]
- Campbell DJ Circulating and tissue angiotensin systems. J Clin Invest 1987; 79:1-7.[Web of Science][Medline]
[Order article via Infotrieve]
- Erman A., Winkler J., Chen-Gal B. et al. Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man. J Hypertens 1991;9:1057-62.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Anderson S., Jung FF, Ingelfinger JR Renal renin-angiotensin system in diabetes:functional, immunohistochemical, and molecular biological correlation. Am J Physiol 1993; 265:F477-86.[Web of Science][Medline]
[Order article via Infotrieve]
- Ziyadeh FN, Goldfarb S., Kern EFO. Contemporary issues in nephrology. In: Brenner BM and Stein JH (eds). The Kidney in Diabetes Mellitus. New York: Churchill Livingstone, 1989;87-113.
- Rabkin R., Shecter P., Dong Shi J., Boner G. Protein turnover in the hypertrophying kidney. Miner Electrolyte Metab 1996; 22:153-6.[Web of Science][Medline]
[Order article via Infotrieve]
- Defendini R., Zimmerman EA, Weare JA, Alhenc-Glas F., Erdos EA Angiotensin-converting enzyme in epithelial and neuroepithelial cells. Neuroendocrinol 1983; 37: 32-40.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Bakris GL,Akerstrom V., Re RN Insulin, angiotensin II antagonist and converting enzyme inhibition: effect on human mesangial mitogenicity and endothelin. Hypertension 1991; 3:326-31.
Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 3,
193-198 (2001)
DOI: 10.3317/jraas.2001.027
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
H. J. Han, S. H. Park, and Y. J. Lee
Signaling cascade of ANG II-induced inhibition of {alpha}-MG uptake in renal proximal tubule cells
Am J Physiol Renal Physiol,
April 1, 2004;
286(4):
F634 - F642.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
