RENAL VASCULAR INDUCTION OF TGF-BETA-2 AND RENIN BY POTASSIUM-DEPLETION

Recently, we have found that transforming growth factor (TGF)-beta2 an d renin are abundantly expressed in the juxtaglomerular apparatus (JGA ) of dehydrated mice. Since potassium (K+) depletion also stimulates r enin and induces hypertrophy of the JGA, we examined the ability of th is maneuver to stimulate TGF-beta isoforms and renin in renovascular t issue 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) f or 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 de prived for three days. Potassium-depleted animals experienced severe g rowth retardation but kidney weight increased significantly. Potassium depletion induced both TGF-beta2 and renin immunoreactivity in renal arterioles and the JGA but had no effect on TGF-beta1 and TGF-beta3 is oforms. To determine the role of circulating angiotensin II in the sti mulation of TGF-beta2 by potassium depletion, a group of potassium-dep leted rats received enalapril (100 mg/liter) in the drinking water. Th e addition of converting enzyme inhibitor increased both the intensity of TGF-beta2 and renin staining as well as the number of cells positi vely stained. Our results demonstrate that K+ depletion induces TGF-be ta2 and renin in renal arterioles and in the JGA. Furthermore, circula ting angiotensin II is not responsible for the increase in the local e xpression of TGF-beta2. These findings suggest that TGF-beta2 may be a n important mediator of JGA hypertrophy. The simultaneous induction of TGF-beta2 with renin suggests that these factors may be coregulated.