Coagulation Factors Are Activators Of Human Plasma “Prorenin”

We have demonstrated that human plasma “prorenin”, an inactive precursor of the blood pressure regulating enzyme renin, can be activated by cold, e.g. -4 to +4°C for 1-30 days (Can. J. Physiol. Pharmacol. 51:705, 1973). Several workers have reported cold activation of the coagulation system. Suspecting a link between these two cold- activated enzyme systems, we established that in factor XII deficient plasma, the rate of cold activation of prorenin is halved (Lancet i, 1313, 1978). Trypsinization of plasma can mimic within 1 minute the effect of prolonged cold (Circ. Res. Suppl . 1, 41:171, 1977), and can overcome specific coagulation factor deficiencies in varying degrees. FXII, VII, V, and especially FX deficient plasmas, all have subnormal basal active renin levels, implying an impaired state of prorenin conversion in vivo. FXII deficientplasma activates least by cold, suggesting special importance of FXII for operation of cold activation. All the plasmas activate better with 0.5 mg trypsin/ml plasma than with cold, except FX, suggesting that it especially mediates tryptic activation. Increasing the trypsin concentration corrects for factor deficiencies in varying degrees, implying some non-specificity and interchangeability of factor requirements for prorenin activation. Our data point to a hierarchy of factor importance, and to a “cascade7#x201D; of prorenin activation, by which plasma renin content can be rapidly increased. Thus, plasma renin activity is a function of renal release of renin, plus renin formation from renal (and possibly extrarenal) prorenin by an activation process involving the coagulation system.