Heterogeneity of Renin Substrate in Human Plasma: Effect of Pregnancy and Oral Contraceptives

Summary

The electrophoretic mobility of renin substrate in human plasma was determined by electrophoresis of the plasma on a cylinder of polyacrylamide gel, followed by slicing the gel, incubation of each slice with human renin, EDTA, and BAL, and determination of the angiotensin formed by radioimmunoassay. In the plasma of normal males and females, a single large peak of renin substrate was found with an electrophoretic mobility somewhat less than that of albumin. In addition, a series of three or four very small peaks of renin substrate with lesser electrophoretic mobility were also observed, the second peak from the origin being the largest of the minor peaks. The peaks, in order of increasing mobility were labeled A through E, E being the large major peak of renin substrate. Occasionally, but not consistently, observed were two or three small peaks of renin substrate with electrophoretic mobilities greater than that of the major peak. Thus, there are five and possibly as many as eight electrophoretically distinguishable renin substrates present in normal human plasma.

In women taking oral contraceptives the pattern of renin substrates is different from that of women not taking such medication. Peaks A and B are significantly increased. In pregnant women a different pattern of renin substrates is found; the minor peaks being markedly increased, especially B, C, and D. Plasma of patients with cirrhosis of the liver and of patients subjected to bilateral nephrectomy were also examined. The pattern of renin substrates in these did not differ significantly from normal, except that the quantities of all the variants of renin substrate, including the major peak, were greatly reduced in some of the patients with cirrhosis.

We thank Drs. E. Haas and H. Goldblatt for the gift of renin and Dr. E. Clark for providing us with blood samples from pregnant and nonpregnant women.