An acidic kininogenase in rat ventricular myocardium

Area of Science:

• Biochemistry
• Cardiology
• Enzymology

Background:

• Canine ventricles possess a cathepsin D-like kininogenase, potentially offering cardioprotection during ischemia.
• This study investigates a similar kininogenase in rat hearts under normal and ischemic conditions.

Purpose of the Study:

• To identify and characterize a cathepsin D-like kininogenase in rat ventricles.
• To determine the enzyme's role in normal and ischemic rat hearts.
• To assess the impact of ischemia on kininogenase activity and kinin levels.

Main Methods:

• Aqueous ventricular extracts were assayed for bradykinin-like immunoreactivity release from kininogens at acidic pH.
• Enzymes were purified via gel filtration and characterized using substrates, protease inhibitors, and isolated rat uteri.
• Ventricular extracts from normal and ischemic rats were compared for kininogenase activity; kinin levels in venous blood were also measured.

Main Results:

• Rat ventricular extracts released bradykinin-like immunoreactivity exclusively from low-molecular-weight kininogen.
• The enzyme was identified as a cathepsin D-like acidic protease (optimum pH 4.7, MW 42.8 ± 4.9 kDa), acting as an arginine amidase.
• Ischemia significantly reduced the ventricular extract's ability to release bradykinin-like immunoreactivity and increased free kinin levels in venous blood.

Conclusions:

• Rat ventricles harbor a cathepsin D-like acidic protease capable of cleaving low-molecular-weight kininogen to generate bradykinin-like immunoreactivity.
• This protease may play a protective role in the heart during ischemic events.