Angiotensin II Receptors in the Kidney: Location and Distribution
Angiotensin II receptors are expressed in both the vascular (blood vessel) side and the tubular side of the kidneys, with AT1 receptors predominantly found in afferent and efferent arterioles, glomeruli, and proximal tubules in normal animals and humans. 1
Distribution of Angiotensin II Receptor Types
AT1 Receptors (Predominant in Adult Kidneys)
- AT1 receptors are expressed in afferent and efferent arterioles (vascular side), glomeruli, and proximal tubules (tubular side) 1
- AT1 receptors mediate most of the known biologic functions of Angiotensin II, including vasoconstriction, growth promotion, and profibrotic effects 1
- AT1 receptors on the efferent arteriole cause more potent constriction than on the afferent arteriole, helping maintain glomerular filtration rate (GFR) during states of renal hypoperfusion 1
AT2 Receptors
- AT2 receptors are highly expressed in fetal kidneys but have much lower expression in adult kidneys 2
- AT2 receptors appear to counterbalance AT1 receptors by mediating vasodilation and promoting natriuresis 3, 4
- AT2 receptors are important for renal development but are weakly expressed in adult animals 2
Functional Significance of Receptor Location
Vascular Effects
- Angiotensin II causes potent constriction in both afferent and efferent arterioles 2
- The efferent arteriolar constriction is particularly important for maintaining glomerular filtration pressure during states of reduced renal perfusion 5
- Angiotensin II constricts the efferent arteriole to a greater extent than the afferent arteriole, which helps maintain glomerular hydrostatic pressure and GFR despite hypoperfusion 1
Tubular Effects
- AT1 receptors in the proximal tubules directly influence sodium transport and reabsorption 5, 4
- The combined vascular and tubular effects of Angiotensin II create a powerful system for regulating blood pressure and volume homeostasis 5
Signaling Mechanisms
- AT1 receptor signaling involves Gq/11-protein and protein kinase C activation 2
- Angiotensin II causes constriction of the afferent arteriole primarily by stimulating calcium entry via voltage-sensitive, L-type channels 2
- Effects on the efferent arteriole are primarily due to calcium release from intracellular stores and calcium entry through voltage-independent channels 2
Clinical Implications
- ACE inhibitors and ARBs block the effects of Angiotensin II on AT1 receptors, causing efferent vasodilation 1
- This vasodilation can lead to an initial decrease in GFR but may provide long-term renoprotective effects by reducing glomerular pressure 1
- In patients with renal artery stenosis or volume depletion, blocking Angiotensin II can cause acute renal failure due to the loss of efferent arteriolar tone 1
Understanding the distribution of Angiotensin II receptors in both the vascular and tubular compartments of the kidney is essential for comprehending the complex effects of RAS inhibitors on renal function and their therapeutic applications in various clinical scenarios.