RAAS Receptors in the Kidney
The kidney expresses two major angiotensin II receptor types: AT1 receptors (type 1) and AT2 receptors (type 2), along with the Mas receptor for angiotensin-(1-7), and the (pro)renin receptor. 1
Primary Angiotensin II Receptors
AT1 Receptors (Angiotensin II Type 1 Receptor)
AT1 receptors are the dominant functional receptors in the kidney, expressed in:
- Afferent and efferent arterioles
- Glomeruli (including mesangial cells and podocytes)
- Proximal tubules
- Distal convoluted tubules
- Cortical collecting ducts 1, 2
The AT1 receptor mediates virtually all known biological functions of angiotensin II through receptor-selective mechanisms 1. When activated, AT1 receptors cause preferential vasoconstriction of efferent arterioles, reducing renal blood flow while initially maintaining glomerular filtration rate 3. This receptor drives pathological mechanisms including vasoconstriction, cellular proliferation, profibrotic effects, and extracellular matrix accumulation 1.
AT2 Receptors (Angiotensin II Type 2 Receptor)
AT2 receptors are also present in the kidney, found in:
- Glomeruli
- Proximal convoluted tubules 1
AT2 receptors counterbalance AT1 receptor effects, promoting vasodilation, inhibiting cellular proliferation and hypertrophy, stimulating nitric oxide production, and enhancing natriuresis 4. While less studied than AT1 receptors, they play important regulatory roles in renal physiology.
Alternative RAAS Pathway Receptors
Mas Receptor
The Mas receptor serves as the G-protein coupled receptor for angiotensin-(1-7), representing the "protective arm" of the RAAS 5. This receptor antagonizes angiotensin II signaling through AT1 receptor modulation and contributes to:
- Vasodilation
- Anti-inflammatory effects
- Reduced vascular resistance 5
The ACE2/Ang-(1-7)/Mas receptor pathway is progressively upregulated in the kidney during certain physiological states and provides counterregulatory balance to the ACE/Ang II/AT1 receptor axis 5.
(Pro)renin Receptor
The (pro)renin receptor is expressed in the kidney and plays crucial roles in developmental and physiological processes through multiple signaling pathways, including Wnt/β-catenin and mitogen-activated protein kinase pathways 5.
Clinical Significance
These receptors represent the primary therapeutic targets for RAAS inhibition in kidney disease. AT1 receptor blockade with angiotensin receptor blockers (ARBs) or ACE inhibitors (which reduce angiotensin II available for AT1 receptor activation) forms the cornerstone of treatment for proteinuric chronic kidney disease, diabetic nephropathy, and hypertension 3, 6.
The distribution of these receptors throughout different nephron segments—particularly the presence of all RAAS components except ACE in proximal convoluted tubules—emphasizes their integral involvement in sodium and water handling 2. Understanding receptor localization helps explain why RAAS inhibition produces both beneficial hemodynamic effects (efferent arteriolar vasodilation increasing renal blood flow) and transient functional changes (initial GFR reduction) 3.
Human studies differ from rodent models in one important aspect: humans and primates have a single AT1 receptor, while mice and rats have two distinct AT1 receptor subtypes (AT1A and AT1B) 7.