It has been shown that chronic CsA treatment is associated with increased expression of an acidic renin isoform and the development of arteriolopathy in rat kidney. Since dietary sodium restriction enhances these effects, it is hypothesized that renal renin enzymatic activity also will be changed by these conditions. Male Sprague Dawley rats received a LS diet for 3 (n=4) or 5 (n=4) weeks. In addition, an equal number of rats in each group received CsA 25 mg/kg/d orally, a dose known to cause renal toxicity. Kidneys were removed and homogenized. Renin enzymatic activity was measured for 1 hr at 37°C in rat kidney homogenate at pH 6.2, the optimum pH, and pH 5.2. Angiotensin I assayed by RIA indicated renin enzymatic activity in the samples. Data are expressed as ng AI/ mg protein/hr. Table

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Mean renin enzymatic activity was higher at pH 5.2 in all groups. This difference was significantly greater in 5wk LS+CsA kidneys compared to the same samples assayed at pH 6.2. These data suggest that there may be proportionally more acidic renin in kidneys of LS and LS+CsA rats which is significantly greater after 5 weeks of treatment with CsA. It is speculated that progressive kidney accumulation of an acidic renin isoform has a role in the development of coexisting CsA-mediated renal arteriolopathy.