Optimum tryptic activation of inactive renin in human plasma is independent of endogenous anti-tryptic activity

1. Plasma samples from 31 normal subjects were treated (at 4 degrees C, pH 7.0, for 2 min) with different concentrations of trypsin (500, 1000, 2000, 3000 and 4000 microgram/ml) in order to assess which concentration yielded the maximum activation of inactive renin. 2. Endogenous antitryptic activity was also measured in all samples; the mean value +/- SD (in microgram of trypsin inhibited by 1 ml of plasma) was 953 +/- 550 microgram/ml (range 34-1800 microgram/ml). 3. In the entire group of subjects the values of trypsin-activated renin measured with trypsin at 2000 microgram/ml were significantly higher than those obtained with lower or higher trypsin concentrations. 4. With subjects divided into subgroups according to their endogenous anti-tryptic activity, the maximum yield of activation was reached with trypsin at 2000 microgram/ml. 5. No significant correlations were found between single values of active, inactive or trypsin-activated renin and the corresponding levels of endogenous anti-tryptic activity. However, a weak but significant correlation (r = 0.39, P less than 0.05) was found between single values of anti-tryptic activity and the corresponding percentage of activation of inactive renin. 6. Thus the maximum activation of inactive renin at 4 degrees C for 2 min is obtained with trypsin at 2000 microgram/ml independently of the corresponding endogenous anti-tryptic activity. It is not excluded that the content of protease inhibitors in human plasma might affect the proportion in vivo of circulating active and inactive renin.