Changes in the cardiovascular nitric oxide pathway in cyclosporin-A treated rats.
Cyclosporin A (CsA), an immunosuppressive agent is known to induce cellular toxic effects by alerting calcium homeostasis. Nitric oxide (NO) has been implicated in a number of physiologic roles in the mammalian cardiovascular system (CVS). The aim of our present study is to investigate the effects of CsA on the rat CV NO pathway. We measured iNOS and cNOS activities in the 100,000 g soluble fraction of ventricles and serum nitrite (NO2-) and nitrite (NO3-) levels in rats treated with 25 mg/kg or 50 mg/kg body weight of CsA/24 hr in olive oil. CsA inhibited cNOS activity of rat ventricles and failed to bring about changes in their iNOS activity. Serum NO2-/NO3- levels were elevated in CsA treated tars. Most of these changes were found to be statistically significant (P < 0.01) at 50 mg/kg body wt of CsA. It is likely that elevation of serum NO2-/NO3- levels may cause myocardial toxicity by alerting rat CV NO pathway.
Rao
M R
MR
Department of Medicine, University of Mississippi Medical Center, Jackson, USA.
Hutcheson
A E
AE
Markov
A K
AK
D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D009206:Myocardium / Q000201:enzymology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D007166:Immunosuppressive Agents; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D016572:Cyclosporine; D019001:Nitric Oxide Synthase