Dietary salt enhances glomerular endothelial nitric oxide synthase
through transforming growth factor-[beta]1.
Ying, Wei-Zhong, and Paul W. Sanders.
Nephrology Research and Training Center, Comprehensive Cancer
Center, and Cell Adhesion and Matrix Research Center, Division of
Nephrology, Department of Medicine and Department of Physiology &
Biophysics, University of Alabama at Birmingham, Birmingham, AL
35294-0007. Department of Veterans Affairs Medical Center,
Birmingham, AL 35233
APStracts 5:0064F, 1998.
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 four 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-[beta]1 (TGF-[beta]1) (Am.
J. Physiol. 274 (Renal Physiol. 43), (in press), 1998), studies were
then conducted to examine the interaction between NOS3 and TGF
-[beta]1. Glomerular steady-state levels of mRNA of NOS3 and TGF
-[beta]1 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-[beta]1, which in turn augmented NO production
through NOS3.
Received 21 November 1997; accepted in final form 9 March 1998.
APS Manuscript Number F366-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 9 March 1998