Tubuloglomerular feedback is initiated by delivery of:

- The rate of NaCl delivery to the distal nephron significantly influences the RBF and GFR; the mechanism is called Tubuloglomerular (TG) feedback. The mechanism is based on 3 components: (i) A sensor: Cells in the macula densa. (ii) A signal: NaCl delivery to the distal tubule. (iii) An effector: Vascular smooth muscle cells within the wall of the afferent aeriole. When filtration increases, the increased NaCl delivery to the macula densa triggers vasoconstriction of the afferent aeriole. This results in a decrease in RBF and hence a decrease in GFR,reducing the NaCl delivery to the macula densa/distal tubules. The vasoconstriction is thought to be mediated by adenosine . If GFR and NaCl delivery to distal tubule are decreased, a decrease in ATP and adenosine formation occurs. There is the release of NO that produces vasodilatation, causing increased RBF and GFR. As more NaCl enters through the NKCC-2 transpoer located in the apical membrane (TAL), it stimulates the release of ATP through ATP-conducting ion channels located in the basolateral membrane of macula densa cells. This results in the opening of Ca2+ channels and an increase in intracellular , resulting in vasoconstriction and fall in GFR. Loop diuretics are known to blunt the TG feedback due to their action on the NKCC transpoer.