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

Recently, we have found that transforming growth factor (TGF)-beta2 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-beta2 and renin immunoreactivity in renal arterioles and the JGA but had no effect on TGF-beta1 and TGF-beta3 isoforms. To determine the role of circulating angiotensin II in the stimulation of TGF-beta2 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-beta2 and renin staining as well as the number of cells positively stained. Our results demonstrate that K+ depletion induces TGF-beta2 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-beta2. These findings suggest that TGF-beta2 may be an important mediator of JGA hypertrophy. The simultaneous induction of TGF-beta2 with renin suggests that these factors may be coregulated.