Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting

Area of Science:

• Nephrology
• Cardiovascular Physiology
• Pharmacology

Background:

• The local renin-angiotensin system (RAS) in the kidney is complex and not fully understood.
• Multiple components, receptors, and metabolites of the RAS exist within the kidney.
• The kidney RAS plays a role in cardiovascular diseases, with renal angiotensin II type 1 (AT₁) receptors often implicated.

Purpose of the Study:

• To provide a unifying view of local angiotensin formation in the kidney.
• To explain how existing and novel drugs affect kidney angiotensin formation.
• To elucidate the mechanisms by which drugs altering the renal RAS confer renoprotection.

Main Methods:

• Review of current literature on local kidney angiotensin formation.
• Analysis of proposed mechanisms for synthesis and uptake of RAS components.
• Examination of the roles of different angiotensin metabolites and receptors.
• Evaluation of the impact of various drugs on the renal RAS and renoprotection.

Main Results:

• Local angiotensinogen and prorenin synthesis occur in kidney tubules.
• Filtered plasma-derived RAS components can be taken up by kidney cells.
• Angiotensin-(1-7) and its Mas receptor, along with AT₂ receptors, are renoprotective.
• Novel drugs like angiotensin receptor/neprilysin inhibitors and SGLT2 inhibitors demonstrate cardiovascular efficacy via renal RAS modulation.

Conclusions:

• A unified understanding of kidney angiotensin formation is presented.
• Existing and novel drugs exert renoprotection by interfering with kidney angiotensin formation.
• The degree of renoprotection by novel drugs is linked to their impact on the renal RAS.