Departments of Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

Correspondence: Dr Jürgen Schnermann, University of Michigan, Department of Physiology, Medical Science Building II, #7712, Ann Arbor, Michigan 48109–0622, USA. E-mail jbsch@umich.edu

Abstract

Tubuloglomerular feedback: New concepts and developments. Luminal [NaCl] 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 NaCl excretion. During long-lasting perturbations of MD [NaCl], 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 [NaCl], 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 [NaCl] 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.