Cryoactivation and tryptic activation of blood 'prorenin' in normal man and animals

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Abstract
Plasma and serum of healthy subjects apparently contain a precursor form of renin, or 'prorenin,' which can be activated by the ice-cold temperature at which samples are customarily handled for prolonged periods in laboratories and blood banks. The effect of such prior cryoactivation for 9 days at 4 °C is to increase subsequent plasma renin activity (PRA) at 37 °C by 108 ± 16.3% (mean ± SE) over the nonactivated control value (P < 0.001). At a lower temperature (−4 °C), the cryoactivation effect is considerably greater than at 4 °C. Cryoactivation is not obliterated by the prefreezing of plasma, or reduced by inclusion of bacteriostats. Nor is it attributable to any detectable reduction in angiotensinase activity. In rats, cryoactivation at 4 °C is much lower than in humans, suggesting a marked species difference either in prorenin concentration or in the rapidity of its spontaneous conversion after blood collection. Trypsin at near-optimal concentrations also consistently activates human plasma prorenin, whether at 4, 23, or 37 °C indicating that cold is not an essential concomitant of tryptic activation. In excess, the magnitude of which varies among individuals, trypsin at first produces activation and later a decline in PRA, probably due to degradation of the reactants (prorenin, renin, angiotensinogen) and of the initial product (angiotensin I). The identity of angiotensin I in activated and control plasmas can be established by specific radioimmunoassay, and bioassay. Our data indicate that tryptic activation involves little direct production of angiotensin I but rather converts prorenin, thereby enhancing the angiotensin generating capacity of the plasma renin system itself. Tryptic activation in plasma of anaesthetized dogs is lower than in humans, but higher than in conscious or anaesthetized rabbits in whom the effect appears to be slight. In anaesthetized rats there is virtually no tryptic activation, which is in line with the results by cryoactivation. Since the renin–angiotensin systems of dogs, rabbits, and rats have been extensively studied in experimental models of human hypertension, these observed departures from human levels of cryoactivation and tryptic activation of prorenin deserve further investigation.