From the Guidelines
Afferent arteriolar vasodilation in the context of glomerulotubular feedback is primarily caused by prostaglandins, nitric oxide, and adenosine at low concentrations, while vasoconstriction is mediated by angiotensin II, thromboxane A2, endothelin, and sympathetic nervous system activity. In the regulation of afferent arteriolar tone, several key players are involved. The vasodilators include:
- Prostaglandins, especially PGE2 and PGI2, which increase renal blood flow and glomerular filtration rate 1
- Nitric oxide (NO), a potent vasodilator
- Adenosine, at low concentrations, which also promotes vasodilation
On the other hand, vasoconstriction of the afferent arteriole is mediated by:
- Angiotensin II, a key component of the renin-angiotensin-aldosterone system (RAAS) 1
- Thromboxane A2
- Endothelin
- Sympathetic nervous system activity, via norepinephrine
- Adenosine at high concentrations, which has a paradoxical effect compared to its vasodilatory action at low concentrations
The tubuloglomerular feedback mechanism specifically involves adenosine, produced when increased sodium delivery to the macula densa triggers ATP release and subsequent conversion to adenosine, causing vasoconstriction of the afferent arteriole 1. This complex interplay of vasodilators and vasoconstrictors is essential for maintaining stable glomerular filtration and renal autoregulation, and is crucial for understanding the effects of various medications, such as NSAIDs, ACE inhibitors, and ARBs, on kidney function.
From the Research
Chemicals and Hormones Involved in Afferent Arteriolar Vasodilation and Vasoconstriction
- Prostaglandin E2 is a key mediator of connecting tubule glomerular feedback (CTGF), causing afferent arteriole (Af-Art) dilation by binding to its type 4 receptor (EP4) 2
- Adenosine triphosphate (ATP) is liberated from macula densa cells in response to increased tubular NaCl delivery, and its breakdown to adenosine mediates efferent arteriole (Ef-Art) tubuloglomerular feedback (TGF) 3
- Sodium (Na+) entry via epithelial sodium channels (ENaC) in the connecting tubule initiates CTGF, leading to Af-Art dilation 4, 5, 6
- Increased luminal flow in the connecting tubule induces CTGF activation via ENaC, partially due to flow-stimulated O2- production and independent of nitric oxide synthase (NOS) activity 5
Mechanisms of Afferent Arteriolar Vasodilation and Vasoconstriction
- CTGF is a vasodilator mechanism that antagonizes tubuloglomerular feedback (TGF), a vasoconstrictor mechanism initiated in the macula densa via Na-K-2Cl cotransporters (NKCC2) 4, 6
- TGF causes Af-Art constriction, while CTGF causes Af-Art dilation 4, 6
- The Na/H exchanger (NHE) in the nephron decreases stop-flow pressure (PSF) (Af-Art constriction) when NKCC2 and ENaC are inhibited, suggesting that NHE causes a TGF response in the absence of NKCC2 6
Regulation of Afferent Arteriolar Tone
- The balance between TGF and CTGF regulates afferent arteriolar tone, with TGF causing vasoconstriction and CTGF causing vasodilation 4, 6
- The activity of various Na transporters, including NKCC2, ENaC, and NHE, influences the balance between TGF and CTGF and ultimately regulates afferent arteriolar tone 6