The macula densa sensing mechanism for tubuloglomerular feedback

A series of studies on the signal responsible for initiating the tubuloglomerular feedback (TGF)-mediated changes in SNGFR have utilized a retrograde perfusion technique that permits close control of macula densa segment tubular fluid composition. The feedback response has been demonstrated to be an approximately linear function of luminal NaCl concentration between 15 and 60 mM, with increasing NaCl concentration resulting in lower nephron filtration rate. Feedback responses could be initiated by NaCl and NaBr solutions but not by NaI, NaNO3, NaF, NaHCO3, NaSCN, or Na acetate. All chloride salts tested, in which chloride was accompanied by a univalent cation, elicited a response. The feedback mechanism thus shows a special requirement for chloride or bromide and not for sodium. With the chloride salts the response varied in magnitude depending on the accompanying cation with the following order of decreasing response, Rb+, Na+, Cs+, NH4+, K+, choline+, and Li+, CaCl2 and MgCl2 did not elicit a feedback response. The feedback response was not influenced by large changes in luminal osmolarity by addition of urea, suggesting either that the feedback sensing site is water impermeable or that water movement does not influence the signal. When electrolyte-free solutions are perfused through the loop of Henle in an orthograde direction, sufficient electrolyte may enter the luminal fluid to transiently influence the feedback mechanism.