Role of macula densa NOS in tubuloglomerular feedback.
Recent studies have amply confirmed the robust expression of neuronal nitric oxide synthase (nNOS) in macula densa cells and its function in blunting tubuloglomerular feedback responses. Regulation of nNOS may occur at many levels: (1) transcriptional and translational regulation, which is enhanced by salt restriction and angiotensin II; (2) functional enhancement by L-arginine delivery and uptake via system Y+, which is enhanced during salt loading; (3) structural activation and feedback inhibition provided by postsynaptic density proteins co-expressed with nNOS in the macula densa; (4) competitive inhibition by dimethylarginines, which can be metabolized via NG, NG dimethylarginine dimethylaminohydrolase co-expressed with nNOS in the macula densa; and (5) intracellular activation linked to changes in [Ca++] or pH during luminal Na+ reabsorption. Nitric oxide, once formed, can be degraded by O2- produced principally in the interstitium between the macula densa and afferent arteriole and in the wall of the arteriole. In genetic hypertension, tubuloglomerular feedback responses are enhanced, in part at least because of diminished buffering by macula densa NO and enhanced O2- generation in the juxtaglomerular apparatus. These recent studies highlight the importance of the macula densa nitric oxide-tubuloglomerular feedback system in adapting glomerular hemodynamics and renal function to changes in salt intake, and define potentially important defects in models of genetic hypertension.
Georgetown University Medical Center, Washington, DC, USA. wilcoxch@gunet.georgetown.edu
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D000818:Animals; D001120:Arginine / Q000494:pharmacology; D005246:Feedback; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology*; D007686:Kidney Tubules, Distal / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I
D001120:Arginine; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I