Dietary salt modulates renal production of transforming growth factor-beta in rats.
Transforming growth factors (TGF) are potent multifunctional polypeptides that are involved in renal function and glomerular sclerosis. We postulated that dietary salt modified renal production of TGF-beta. An increase in dietary salt produced sustained increases in steady-state levels of mRNA for TGF-beta 1, -beta 2, and -beta 3 in the rat kidney. While serum concentration of TGF-beta 1 did not change, the 8.0% NaCl diet increased urinary excretion of TGF-beta 1, indicating enhanced renal production was the source of TGF-beta 1. Increasing urinary flow rates with diuretics did not further increase synthesis of TGF-beta 1 in animals receiving the 8.0% NaCl diet. The 8.0% NaCl diet increased production of TGF-beta 1 in both glomeruli and tubules, although active TGF-beta 1 was secreted in greater amounts only from glomeruli. Enhanced glomerular production of both inactive and active TGF-beta 1 induced by the 8.0% NaCl diet was inhibited by tetraethylammonium (TEA) and not glybenclamide. Cardiac production of TGF-beta 1 also increased on the 8.0% NaCl diet but was not affected by TEA. The results demonstrated that increased dietary salt augmented glomerular TGF-beta production by a mechanism that included a TEA-sensitive potassium channel. Dietary salt, by facilitating glomerular expression of TGF-beta, may directly promote development of glomerulosclerosis.
Ying
W Z
WZ
Nephrology Research and Training Center, University of Alabama at Birmingham 35294-0007, USA.
Sanders
P W
PW
D000818:Animals; D004032:Diet; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage* / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000652:urine
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D012965:Sodium Chloride; D019789:Tetraethylammonium