Cell and molecular studies of renin secretion

Area of Science:

• Renal Physiology
• Molecular Biology
• Pharmacology

Background:

• Control of renin synthesis and secretion is crucial for blood pressure regulation.
• Previous studies focused on whole-kidney renin levels, neglecting cellular control mechanisms.
• The role of vascular smooth muscle cells in renin production during maturation is unclear.

Purpose of the Study:

• To investigate the regulation of renin gene expression in fetal and adult rats.
• To examine the effects of angiotensin converting enzyme (ACE) inhibition on renin synthesis.
• To characterize renin-secreting cells at the cellular level using a novel assay.

Main Methods:

• Studied renin gene expression in fetal and adult rat kidneys.
• Administered enalapril (ACE inhibitor) with and without angiotensin II (AII).
• Utilized the reverse hemolytic plaque assay (RHPA) to study individual renin-secreting cells.
• Employed transmission electron microscopy (EM) for cellular ultrastructure analysis.

Main Results:

• Adult renal feeder vessels, normally renin-deficient, gained renin synthesis capacity after ACE inhibition.
• ACE inhibition increased the number of renin-secreting cells by 15-fold and renin release by 3-fold.
• Angiotensin II partially reversed the effects of ACE inhibition on renin production.
• Transmission electron microscopy revealed modified vascular smooth muscle cells with secretory granules.

Conclusions:

• ACE inhibition reactivates renin synthesis in adult renal feeder vessels, mimicking fetal patterns.
• Angiotensin II plays a role in inhibiting renin gene expression.
• The individual renin-secreting cell is a modified vascular smooth muscle cell, demonstrating plasticity in renin production.