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Reduction of myocardial nitrosyl complex formation by a nitric oxide scavenger prolongs cardiac allograft survival. J Cardiovasc Pharmacol 2000 Jan;35(1):114-20

Date

01/12/2000

Pubmed ID

10630741

DOI

10.1097/00005344-200001000-00015

Scopus ID

2-s2.0-0033986282   19 Citations

Abstract

Nitric oxide synthase (NOS) inhibitors have been shown to reduce NO but yield conflicting results on cardiac allograft survival. In this study, we provide an alternative approach specifically to examine the efficacy of a NO scavenger on nitrosyl complex formation and graft survival in a model of heterotopic cardiac transplantation. Efficacy was examined under both acute and chronic conditions (i.e., without or with immunosuppression, respectively). Electron paramagnetic resonance (EPR) spectroscopy of frozen myocardial tissue from untreated allografts showed progressive increases in nitrosylheme and nitrosomyoglobin before graft failure. These signals were not seen in either isografts or native hearts of allograft recipients. Both plasma nitrate plus nitrite and myocardial nitrosyl complex formation in cardiac allografts were significantly decreased in recipient animals treated with the NO scavenger, NOX-100, or by low-dose cyclosporine (CsA). Both interventions were nearly equivalent in significantly prolonging graft survival. The short-term combination treatment of both NOX-100 plus CsA completely eliminated myocardial nitrosyl complex formation and synergistically prolonged graft survival. Long-term combination drug treatment (days 0-100) followed by cessation of therapy resulted in permanent graft acceptance with no evidence for nitrosyl complex formation. These studies support a role of NO in cardiac allograft rejection. Furthermore, these studies indicate a potential therapeutic value of NO scavengers in preventing organ rejection.

Author List

Pieper GM, Cooper M, Johnson CP, Adams MB, Felix CC, Roza AM

Authors

Christopher P. Johnson MD Professor in the Surgery department at Medical College of Wisconsin
Allan M. Roza MD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cyclosporine
Electron Spin Resonance Spectroscopy
Free Radical Scavengers
Free Radicals
Graft Survival
Heart Transplantation
Immunosuppressive Agents
Iron
Myocardium
Nitrates
Nitric Oxide
Nitrites
Nitrogen
Rats
Rats, Inbred Lew
Rats, Sprague-Dawley
Thiocarbamates
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00