Effect of cyclosporin A on rat kidney catecholamines.
The immunosuppressive agent, Cyclosporin A, (CsA) has been associated with nephrotoxicity and hypertension. The mechanism for these effects are not known. We therefore determined the levels of the catecholamines; epinephrine (EPI), norepinephrine (NE) and dopamine (DA) and some of their metabolites; epinine, dihydroxyphenyl-acetic acid (DOPAC), homovanillic acid (HVA), metanephrine (ME) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the kidneys of rats treated intraperitoneally with either CsA (120 micrograms/kg/body wt/day) or control vehicle (1 ml olive oil/kg body wt/day). Six control or CsA treated rats were sacrificed at 1 hour or 24 hours after a single treatment or after 7 days of daily treatment. Renal catecholamine levels were determined using HPLC-amperometric detector. Treatment with CsA increased renal NE and EPI levels by 59% and 70% respectively within 1 hour. In the rats sacrificed 24 hours after treatment, renal NE, EPI and DA levels were similar to or less than the control levels. Treatment with CsA for 7 days resulted in marginal increases in renal NE (22%) and EPI (30%). These changes were associated with a significant decrease in the levels of catecholamine metabolites in the CsA treated kidneys as compared to the controls. The above findings suggest that increases in renal catecholamines may be involved in the CsA-induced hypertension and nephrotoxicity, perhaps by increasing renovascular resistance.
Duruibe
V A
VA
Clinical Pharmacology Research Unit, College of Pharmacy, Florida A&M University, Miami.
Okonmah
A
A
Panton
L
L
Blyden
G T
GT
D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002395:Catecholamines; D003524:Cyclosporins; D007980:Levodopa; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine