Dietary salt enhances glomerular endothelial nitric oxide synthase through TGF-beta1.
Dietary salt controls production of nitric oxide (NO), a potent paracrine relaxation factor involved in glomerular filtration and salt excretion. We hypothesized that glomerular NO production was enhanced through endothelial nitric oxide synthase (NOS3). Rats in metabolic cages were studied after 4 days on 0.3% (Lo-salt) or 8.0% (Hi-salt) NaCl diet. Steady-state mRNA and protein levels of NOS3 and calcium-dependent NO production of isolated glomeruli from Hi-salt animals were greater than those values observed in glomeruli from Lo-salt rats. Because dietary salt enhanced glomerular production of transforming growth factor-beta1 (TGF-beta1) [W.-Z. Ying and P. W. Sanders. Am. J. Physiol. 274 (Renal Physiol. 43): F635-F641, 1998], studies were then conducted to examine the interaction between NOS3 and TGF-beta1. Glomerular steady-state levels of mRNA of NOS3 and TGF-beta1 directly correlated (r2 = 0. 946; P < 0.0001). A neutralizing antibody to TGF-beta reduced NOS3 protein and NO production in cultured glomeruli from Hi-salt animals to levels seen in the Lo-salt glomeruli. Thus dietary salt increased glomerular expression of TGF-beta1, which in turn augmented NO production through NOS3.
Ying
W Z
WZ
Nephrology Research and Training Center, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294-0007, USA.
Sanders
P W
PW
D000818:Animals; D004039:Diet, Sodium-Restricted; D004231:Diuresis / Q000187:drug effects; D002149:Energy Intake; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III; D011188:Potassium / Q000652:urine; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012982:Sodium, Dietary / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000502:physiology
D012333:RNA, Messenger; D012982:Sodium, Dietary; D016212:Transforming Growth Factor beta; D019789:Tetraethylammonium; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D011188:Potassium