Tissue renin: focus on vascular angiotensin formation

Area of Science:

• Cardiovascular Physiology
• Renal Physiology
• Endocrinology

Background:

• The renin-angiotensin system (RAS) plays a crucial role in regulating blood pressure and fluid balance.
• Local production of angiotensin (Ang) peptides within tissues is increasingly recognized, but its significance in vascular beds remains debated.

Purpose of the Study:

• To investigate the local vascular formation of Angiotensin I (Ang I) and Angiotensin II (Ang II) in the rat hindquarter.
• To determine the contribution of plasma-derived renin versus potential local renin synthesis to vascular Ang peptide generation.

Main Methods:

• Utilized isolated, plasma-free perfused rat hindquarters for controlled experimentation.
• Analyzed perfusate using high-performance liquid chromatography and radioimmunoassay to quantify Ang I and Ang II levels.
• Administered captopril and a specific renin inhibitor (H-142) to assess their effects on Ang peptide formation and perfusion pressure.

Main Results:

• Demonstrated spontaneous release of Ang I and Ang II from the hindlimb vasculature.
• Observed that captopril suppressed Ang II and increased Ang I, while bilateral nephrectomy abolished Ang peptide formation.
• Showed that infused renin increased local Ang formation and perfusion pressure, effects inhibited by captopril and H-142.
• Quantified Ang I to Ang II conversion in the vasculature at approximately 75%, fully inhibited by captopril.

Conclusions:

• The rat hindquarter vasculature exhibits significant local formation of Ang I and Ang II.
• This vascular Ang peptide generation is predominantly driven by renin originating from the plasma.
• The findings suggest that while local vascular synthesis of renin is possible, plasma-derived renin is the main contributor to Ang peptide production in this vascular bed.