Cryoactivation of plasma renin

Area of Science:

• Biochemistry
• Physiology
• Enzymology

Background:

• Renin activity is crucial for blood pressure regulation.
• Cryoactivation is a phenomenon where plasma stored at low temperatures exhibits increased renin activity.
• The precise mechanism behind cryoactivation remains incompletely understood.

Purpose of the Study:

• To investigate the mechanism underlying cryoactivation of human plasma.
• To determine if a specific enzyme is responsible for the observed increase in renin activity.
• To explore the role of inhibitors in the cryoactivation process.

Main Methods:

• Human plasma was subjected to cryoactivation at -5°C for 4 days.
• Comparison of cryoactivation with trypsin-induced activation.
• Testing the effect of thiol enzyme inhibitors (N-ethylmaleimide) and serine enzyme inhibitors (soyabean trypsin inhibitor, di-isopropylfluorophosphate - DFP).
• In vivo experiments using rat hemorrhagic shock models.

Main Results:

• Cryoactivation showed a strong correlation with trypsin-induced renin activity increase (r = 0.88).
• N-ethylmaleimide did not inhibit cryoactivation, while soyabean trypsin inhibitor and DFP did.
• Cryoactivated rat plasma exhibited approximately double the renin activity compared to non-cryoactivated plasma after hemorrhagic shock.
• No significant differences in renin or renin substrate concentrations were observed between cryoactivated and non-cryoactivated samples.

Conclusions:

• Cryoactivation of plasma is likely mediated by a trypsin-like serine enzyme.
• The increase in renin activity is attributed to the destruction of an endogenous inhibitor of the renin-renin substrate reaction.
• This mechanism may play a role in physiological responses to stress, such as hemorrhagic shock.