Nitric oxide and tubuloglomerular feedback.
Glomerular filtration is closely coupled to tubular reabsorption by a system of tubuloglomerular feedback (TGF). TGF operates within the juxtaglomerular apparatus (JGA) of each nephron, where changes are sensed in the salt content of fluid at the luminal macula densa and that information is transmitted to the glomerular microvasculature to elicit compensatory changes in single nephron glomerular filtration rate (GFR). Type I nitric oxide synthase (NOS) is expressed in the macula densa. Other NOS isoforms may be produced in the mesangium, and glomerular microvessels. These NOSs are strategically positioned to influence each step of the TGF process. However, micropuncture experiments using NOS antagonists have shown that nitric oxide (NO) does not mediate TGF. Instead, local NOS blockade causes the curve that represents TGF to shift leftward and become more steep. Changes in macula densa NO production may underlie the resetting of TGF, which is required in order to keep the TGF curve aligned with ambient tubular flow as tubular flow changes to accommodate physiologic circumstances. Also, macula densa NO production may be substrate limited and dissociated from NOS protein content. The importance of NO to TGF resetting and the substrate dependence of NO production have both been found during changes in dietary salt.
Welch
W J
WJ
Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
Wilcox
C S
CS
Thomson
S C
SC
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D051546:Cyclooxygenase 2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005246:Feedback; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D017482:Receptors, Thromboxane / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
D007527:Isoenzymes; D008565:Membrane Proteins; D017482:Receptors, Thromboxane; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D003577:Cytochrome P-450 Enzyme System; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases