TY - JOUR
T1 - Tubuloglomerular feedback
T2 - New concepts and developments
AU - Schnermann, J.
AU - Traynor, T.
AU - Yang, T.
AU - Arend, L.
AU - Huang, Y. G.
AU - Smart, A.
AU - Briggs, J. P.
N1 - Funding Information:
Work from our laboratory was supported by National Institutes of Health Grants DK 37448, DK 39255, and DK 40042. We are indebted and grateful to the following for providing breeder pairs of transgenic animals: Drs. T.M. Coffman and M.I. Oliverio, Duke University (AT 1A mutant mice); Drs. J.H. Krege and O. Smithies, University of North Carolina (ACE mutant mice); Drs. P.L. Huang and M.C. Fishman, Massachusetts General Hospital and Harvard University; and Dr. O.A. Carretero, Henry Ford Hospital (NOS I mutant mice).
PY - 1998
Y1 - 1998
N2 - Luminal [NaCI] at the macula densa (MD) has two established effects: regulation of glomerular arteriolar resistance through tubuloglomerular feedback (TGF) and control of renin secretion. TGF acts as a minute-to- minute stabilizer of distal salt delivery, thereby minimizing the impact of random perturbations in filtration and absorption forces on NaCI excretion. During long-lasting perturbations of MD [NaCI], control of renin secretion becomes the dominant function of the MD. The potentially maladaptive effect of TGF under chronic conditions is prevented by TGF adaptations permitting adjustments in glomerular filtration rate to occur. TGF adaptation is mechanistically coupled to the endpoint targeted by chronic deviations in MD [NaCI], the rate of local and systemic angiotensin II generation. Studies of TGF in transgenic mice are expected to provide further insights into the mechanisms mediating between luminal [NaCI] and afferent arterioles. TGF responses are virtually abolished in mice in which either the AT(1A) gene or the angiotensin converting enzyme gene is rendered nonfunctional by homologous recombination. In contrast, TGF responses are unaltered in nitric oxide synthase I knockout mice. Thus, an intact renin-angiotensin system appears to be critical for the TGF signaling pathway.
AB - Luminal [NaCI] at the macula densa (MD) has two established effects: regulation of glomerular arteriolar resistance through tubuloglomerular feedback (TGF) and control of renin secretion. TGF acts as a minute-to- minute stabilizer of distal salt delivery, thereby minimizing the impact of random perturbations in filtration and absorption forces on NaCI excretion. During long-lasting perturbations of MD [NaCI], control of renin secretion becomes the dominant function of the MD. The potentially maladaptive effect of TGF under chronic conditions is prevented by TGF adaptations permitting adjustments in glomerular filtration rate to occur. TGF adaptation is mechanistically coupled to the endpoint targeted by chronic deviations in MD [NaCI], the rate of local and systemic angiotensin II generation. Studies of TGF in transgenic mice are expected to provide further insights into the mechanisms mediating between luminal [NaCI] and afferent arterioles. TGF responses are virtually abolished in mice in which either the AT(1A) gene or the angiotensin converting enzyme gene is rendered nonfunctional by homologous recombination. In contrast, TGF responses are unaltered in nitric oxide synthase I knockout mice. Thus, an intact renin-angiotensin system appears to be critical for the TGF signaling pathway.
KW - Juxtaglomerular apparatus
KW - Micropuncture
KW - Nitric oxide synthase
KW - Renin- angiotensin system
KW - Transgenic mice
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U2 - 10.1046/j.1523-1755.1998.06708.x
DO - 10.1046/j.1523-1755.1998.06708.x
M3 - Article
C2 - 9736251
AN - SCOPUS:0031721055
SN - 0098-6577
VL - 54
SP - S40-S45
JO - Kidney International, Supplement
JF - Kidney International, Supplement
IS - 67
ER -