More on Renin

In an editorial comment (1) on our paper (2), Sealey and Laragh erroneously conclude that the IRMA is a step backward from the traditional enzyme-kinetic plasma renin activity (PRA) assay, and that the new IRMA is not suitable for measuring renin because it comeasures 1–2% of prorenin. They regard the traditional PRA assay as an accurate measure of the in vivo production of angiotensin (Ang) II, the physiologically relevant end product of the renin–angiotensin cascade. In fact, the PRA assay measures the concentration of Ang I that is generated in plasma in vitro after a long incubation period (up to 18 h) under artificial conditions. The PRA assay is an indirect assay of renin and is complicated by the fact that Ang I is usually converted to Ang II and degraded into smaller inactive peptides. Ang I-to-II conversion and Ang I degradation are prevented by lowering the pH of plasma and by adding peptidase inhibitors before the incubation step. Whether this is 100% successful, particularly with such long incubation times, has not been formally tested. These difficulties are not encountered in the direct assay of renin by IRMA.