Cyclosporin A treatment enhances angiotensin converting enzyme activity in lung and serum of rats

Autor: Joseph B. Rosenfeld, J Zabludowski, B Chen-Gal, Arie Erman
Rok vydání: 1990
Předmět:
Zdroj: Journal of Pharmacy and Pharmacology. 42:525-527
ISSN: 2042-7158
0022-3573
DOI: 10.1111/j.2042-7158.1990.tb06614.x
Popis: Nephrotoxicity and arterial hypertension are the most common side effects of treatment with cyclosporin A (CSA). Its effects on angiotensin converting enzyme (ACE) activity in the renal cortex, lung and serum of nephrotoxic rats have been investigated. Wistar rats were treated with CSA (20 mg kg−1 day−1 i.p.) or vehicle (olive oil containing 10% ethanol) for 14 days. On day 15, the rats were killed and ACE activity determined by radiometric assay using [3H]hippuryl-glycyl-glycine as substrate. CSA treatment resulted in a decrease in creatinine clearance, urine flow and body weight and a significant increase in serum and lung ACE activities (436 ± 9 vs 391 ± 7 nmol mL−1 min−1, P < 0.001; 184 ± 8 vs 142 ± 10 nmol mg−1 min−1 P < 0.01, respectively). In contrast, renal cortex ACE activity was reduced in the CSA-treated rats (0.35 ± 0.02 vs 0.51 ± 0.02 nmol mg−1 min−1, P < 0.01). ACE activities in the renal cortex and serum were not affected by treatment with gentamicin (80 mg kg−1 day−1) for 11 days. In rats treated simultaneously with CSA and captopril (50 mg kg−1 day−1) ACE activity in the serum, lung and renal cortex was inhibited by 95, 93 and 92%, respectively. These changes in ACE activity were associated with a decreased systolic blood pressure in the rats receiving CSA and captopril. Therefore, ACE activity in the serum and lung of CSA-treated rats was increased, while its activity in the renal cortex was reduced. This increased activity may support the suggestion that CSA induces hypertension through an angiotensin II-dependent mechanism and/or an increased degradation of vasodilatory kinins.
Databáze: OpenAIRE
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