both vasoconstriction and vasodilation, with perhaps the former in the lower range and the latter in the higher range of NaCl concentrations (2). When feedback regulation of afferent arteriolar tone is prevented by interrupting the feedback loop, and when the sensing mechanism is fully activated by saturating NaCl concentrations, TGF reduces GFR on average by approximately 45% and PGC by approximately 20%. Afferent arteriolar resistance increases by 50% or less, consistent with a radius reduction of approximately 10%, if Poiseuille's law holds. Thus, TGF-induced vasoconstriction is usually limited in magnitude. Modulation A mediating agent is released or generated as a function of changes in luminal NaCl concentration. The size of the TGF response is directly dependent upon these changes. "In part because of the striking effect of deletion of A1 adenosine receptors (A1AR), adenosine generated from released ATP has been proposed as the critical TGF mediator. A modulating agent affects the TGF response without input regarding luminal NaCl. The agents are vasoactive substances that alter either the magnitude or the sensitivity of the TGF response. Factors that decrease TGF sensitivity include: atrial natriuretic peptide nitric oxide The oxidative stress in the macula dense is determined by interactions between nitric oxide (NO) and superoxide (O ). TGF response is normally controlled by the NO generated in the macula densa. cAMP PGI2 high-protein diet The threshold at which the loop of Henle flow rate initiates feedback responses is affected. A high protein diet affects the feedback activity by making the single nephron glomerular filtration rate higher, and the Na and Cl concentrations in early distal tubule fluid lower. The signal eliciting the TG feedback response is affected. The increased load on the kidney of high-protein diet is a result of an increase in reabsorption of NaCl. Connecting tubule glomerular feedback (CTGF): CTGF is initiated by increased sodium concentration at the connecting tubule segment of the nephron and involves the activation of epithelial sodium channel (ENaC). CTGF has the ability to modulate TGF mechanism and is critical in understanding renal damage observed in salt sensitive hypertension and kidney donors. Factors that increase TGF sensitivity include: adenosine thromboxane 5-HETE angiotensin II prostaglandin E2 aldosterone Aldosterone within the connecting tubule lumen enhances connecting tubule glomerular feedback (CTGF) via a nongenomic effect involving GPR30 receptors and sodium/hydrogen exchanger (NHE). Aldosterone inside the connecting tubule lumen enhances CTGF via a cAMP/PKA/PKC pathway and stimulates O2− generation and