Cyclosporin A treatment enhances angiotensin converting enzyme activity in lung and serum of rats.
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)
Erman
A
A
Institute of Nephrology and Hypertension, Beilinson Medical Center, Petah Tikva and Sackler School of Medicine, Tel-Aviv, Israel.
Chen-Gal
B
B
Zabludowski
J
J
Rosenfeld
J B
JB
D000818:Animals; D002216:Captopril / Q000494:pharmacology; D003404:Creatinine / Q000097:blood / Q000652:urine; D003524:Cyclosporins / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D002216:Captopril; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A