Renal vascular induction of TGF-beta 2 and renin by potassium depletion.
Recently, we have found that transforming growth factor (TGF)-beta 2 and renin are abundantly expressed in the juxtaglomerular apparatus (JGA) of dehydrated mice. Since potassium (K+) depletion also stimulates renin and induces hypertrophy of the JGA, we examined the ability of this maneuver to stimulate TGF-beta isoforms and renin in renovascular tissue and the JGA of young rats. Sprague-Dawley rats (50 +/- 5 g) were fed either a control diet or a potassium-deficient diet (< 0.05% K+) for 7, 16, or 21 days. As a control for TGF-beta and renin stimulation, an additional group of animals was fed a normal diet but was water deprived for three days. Potassium-depleted animals experienced severe growth retardation but kidney weight increased significantly. Potassium depletion induced both TGF-beta 2 and renin immunoreactivity in renal arterioles and the JGA but had no effect on TGF-beta 1 and TGF-beta 3 isoforms. To determine the role of circulating angiotensin II in the stimulation of TGF-beta 2 by potassium depletion, a group of potassium-depleted rats received enalapril (100 mg/liter) in the drinking water. The addition of converting enzyme inhibitor increased both the intensity of TGF-beta 2 and renin staining as well as the number of cells positively stained. Our results demonstrate that K+ depletion induces TGF-beta 2 and renin in renal arterioles and in the JGA. Furthermore, circulating angiotensin II is not responsible for the increase in the local expression of TGF-beta 2. These findings suggest that TGF-beta 2 may be an important mediator of JGA hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Ray
P E
PE
Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland.
McCune
B K
BK
Gomez
R A
RA
Horikoshi
S
S
Kopp
J B
JB
Klotman
P E
PE
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D007536:Isomerism; D007606:Juxtaglomerular Apparatus / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D011191:Potassium Deficiency / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D012083:Renin / Q000097:blood / Q000378:metabolism*; D013194:Staining and Labeling; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta; D004656:Enalapril; D012083:Renin