Does angiotensin regulate systemic conversion of prorenin to renin?

Area of Science:

• Renal physiology
• Endocrinology
• Hypertension research

Background:

• The renin-angiotensin system (RAS) plays a crucial role in blood pressure regulation.
• Prorenin circulates in plasma and can be activated to renin, the rate-limiting enzyme in RAS.
• The kidney is a primary source of renin, but extrarenal prorenin sources and activation mechanisms are less understood.

Purpose of the Study:

• To investigate the source and regulation of prorenin after kidney removal (binephrectomy).
• To identify and characterize a potential renal "convertase" enzyme responsible for prorenin activation.
• To determine the effect of angiotensin (Ang) on prorenin and "convertase" activity.

Main Methods:

• Rats underwent binephrectomy, and plasma prorenin levels were measured over 48 hours.
• Renal cortical slices were incubated to detect "convertase" activity.
• Angiotensin I infusion and Angiotensin II addition to tissue incubates were used to assess regulatory effects.

Main Results:

• Plasma prorenin increased ~250% within 12 hours post-binephrectomy, indicating an extrarenal source.
• Active renin decreased, suggesting the loss of a renal prorenin activation mechanism ("convertase").
• Angiotensin I infusion and Angiotensin II inhibited "convertase" activity in vitro and in vivo.

Conclusions:

• The kidney contains a "convertase" that activates circulating prorenin.
• Angiotensin regulates both direct renal renin release and the activity/secretion of this renal "convertase".
• Angiotensin plays a significant role in controlling renin levels through modulation of prorenin activation.