Targeting the renin-angiotensin system: what's new?

Area of Science:

• Cardiovascular Pharmacology
• Biochemistry
• Drug Discovery

Background:

• The renin-angiotensin system (RAS) is crucial in cardiovascular regulation.
• Current drugs like ACE inhibitors and AT1 receptor blockers target the classic RAS pathway.
• Angiotensin peptides can be generated via non-classic pathways, offering alternative therapeutic avenues.

Purpose of the Study:

• To review non-classic pathways of angiotensin peptide generation.
• To discuss the relationship of these pathways to the classic RAS.
• To evaluate the potential effects of inhibiting these alternative pathways.

Main Methods:

• Literature review of established and emerging pathways in RAS.
• Analysis of enzymatic actions (renin, chymase, ACE2, neutral endopeptidase 24.11).
• Discussion of therapeutic implications of inhibiting specific enzymes and pathways.

Main Results:

• Renin remains the primary enzyme for angiotensin I formation, with renin inhibitors offering specificity.
• Chymase, a mast cell protease, generates angiotensin II at inflammatory sites like atherosclerotic plaques.
• ACE2 has protective cardiac effects, and neutral endopeptidase 24.11 degrades angiotensin II and natriuretic peptides.

Conclusions:

• Inhibiting renin blocks downstream metabolites, offering specificity.
• Targeting chymase and ACE2 presents novel therapeutic strategies for cardiovascular conditions.
• Dual inhibitors and advanced therapies like gene therapy may offer long-term hypertension management.