Immunochemical differences between angiotensin I-forming enzymes in man

Area of Science:

• Biochemistry
• Neuroscience
• Endocrinology

Background:

• Renin-angiotensin system (RAS) plays a crucial role in blood pressure regulation.
• Renin, the rate-limiting enzyme in RAS, is primarily known to be present in the kidneys and plasma.
• The presence and function of renin in the human brain are not fully understood.

Purpose of the Study:

• To investigate the presence and characteristics of renin and other angiotensin I-forming activities in the human brain.
• To compare brain-derived angiotensin I production with that of plasma and amniotic fluid.
• To determine if brain renin is immunochemically similar to renal and plasma renin.

Main Methods:

• Incubation of human plasma, amniotic fluid, and brain extracts with human and rat plasma renin substrates.
• Dose-dependent inhibition studies using anti-(human renin) antibody.
• Affinity chromatography using haemoglobin-Sepharose gel to separate angiotensin I-forming activities.

Main Results:

• Human brain extracts produced significantly more angiotensin I with rat renin substrate than with human renin substrate.
• Anti-(human renin) antibody inhibited angiotensin I production in plasma and amniotic fluid but not in brain extracts acting on rat renin substrate.
• Affinity chromatography separated brain activities: one inhibited by anti-renin antibody and another acting on heterologous substrate at acidic pH.

Conclusions:

• A renin, immunochemically identical to renal, plasma, and amniotic fluid renin, is present in the human brain.
• The human brain also possesses a distinct angiotensin I-forming activity that acts on heterologous substrates at acidic pH and is not neutralized by anti-renin antibodies.