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

J Pharm Pharmacol. 1990 Jul;42(7):525-7. doi: 10.1111/j.2042-7158.1990.tb06614.x.

Abstract

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 less than 0.001; 184 +/- 8 vs 142 +/- 10 nmol mg-1 min-1 P less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Captopril / pharmacology
  • Creatinine / blood
  • Creatinine / urine
  • Cyclosporins / antagonists & inhibitors
  • Cyclosporins / therapeutic use*
  • Injections, Intraperitoneal
  • Kidney Cortex / drug effects*
  • Kidney Cortex / enzymology
  • Lung / drug effects*
  • Lung / enzymology
  • Male
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / metabolism*
  • Rats
  • Rats, Inbred Strains

Substances

  • Cyclosporins
  • Captopril
  • Creatinine
  • Peptidyl-Dipeptidase A