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Departments of Internal Medicine I, Anatomy, and Gynecology and Obstetrics, Erasmus University Rotterdam; Department of Physiology, University of Utrecht Utrecht, The Netherlands
Address requests for reprints to: Dr. M. A. D. H. Schalekamp, Department of Internal Medicine I, University Hospital Dykzigt, Room L 253, DT Molewaterplein, 40 3015 GD Rotterdam, The Netherlands.
Direct RIA of renin with monoclonal renin antibodies and indirect RIA with angiotensin I antibodies were performed in plasma of 44 pregnant women, 44 women taking an oral contraceptive (OC), and 54 normal women. The following parameters were measured: immunoreactive renin, naturally occurring enzymatically active renin (active renin), trypsinactivatable inactive renin (prorenin), PRA, and renin substrate.
Immunoreactive renin (mean, 95% confidence interval) was significantly higher in pregnant women (1090; 420–2800 pg/ml; third trimester) than in normal women (248; 101–562 pg/ml; P <0.001) and was lower in OC-treated women (131; 41–415 pg/ ml; P <0.001). Prorenin and active renin also were increased in pregnant women and decreased in OC-treated women. The fraction of renin that was in the active form was lower in pregnant women (4.8; 1.4-18%) than in OC-treated women (8.8; 3.0–25%; P <0.001) and normal women (9.1; 2.9–29%; P <0.001). Renin substrate was increased to comparable levels in pregnant women and OC-treated women, but PRA was increased in pregnant women and normal in OC-treated women.
The maximum velocity per unit weight of renin was the same for active renal renin as for active plasma renin and trypsinactivated plasma prorenin. Maximum velocity and Kmvalues measured in mixtures of purified active renin and renin substrate and the concentrations of active renin and renin substrate measured in whole plasma were entered into the Michaelis- Menten equation for calculating PRA. The calculated values were similar to the measured results in all three groups, indicating that PRA was determined by the molar concentrations of enzyme and substrate. Thus, we found no evidence of unknown substances in plasma interfering with the enzyme-substrate reaction. The percentage of circulating renin in the active form was much lower during pregnancy than in other conditions where the renal release of active renin is stimulated and prorenin is as high as during pregnancy. This suggests that a smaller fraction of prorenin is intrarenally converted into active renin before its release into the circulation or that a larger fraction of circulating prorenin is of extrarenal origin. The finding that PRA is normal during OC treatment suggests that the estrogen-induced increase in renin substrate is compensated for by suppressed renal release of active renin.
* This work was supported by a grant from the Organization of Health Research (Fungo), The Netherlands.
Received January 24, 1986.
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