Tubuloglomerular feedback (TGF) involves macula densa sensing of luminal NaCl concentration. The signaling pathway linking high luminal NaCl to afferent arteriolar vasoconstriction is:

• A Na⁺/H⁺ exchanger (NHE3) activation → intracellular alkalosis → PGE2 release → EP4 vasodilation
• B Cl⁻ sensing via Cl⁻ channel → nitric oxide synthase activation → NO-mediated vasodilation
• C NKCC2 uptake → macula densa renin release → angiotensin II → afferent constriction
• D NKCC2 uptake → ATP/adenosine release → A1 receptor on afferent arteriole → vasoconstriction ✓

Explanation

When GFR is high, increased NaCl delivery to the macula densa is sensed via NKCC2 cotransporter uptake. This elevates intracellular [Cl⁻] and [Na⁺] in macula densa cells, triggering ATP release into the interstitium. ATP is rapidly converted to adenosine, which acts on A1 adenosine receptors on the afferent arteriole, causing vasoconstriction and reducing GFR — a negative feedback loop. At low delivery, macula densa cells release PGE2 and nitric oxide to dilate the afferent arteriole and stimulate renin release. Renin release actually increases with low luminal NaCl, not high.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.