Abstract
The role of nitric oxide (NO) production in acute allograft rejection is not known. In normal human vasculature, nitric oxide synthase is constitutively expressed within endothelial cells (cNOS), and small quantities of NO produced by this pathway mediate vasorelaxation via a cyclic GMP-dependent mechanism. During cardiac allograft rejection, NO may also be produced by the inducible isoform of nitric oxide synthase (iNOS), present in endothelial cells, smooth muscle cells and cardiac myocytes. Unlike cNOS activity, which is an integral part of cardiovascular homeostasis, iNOS activity is a component of the inflammatory response and may have both beneficial and deleterious effects during rejection. Early reports suggested that acute cardiac allograft rejection was associated with an increase in nitric oxide production. The general aim of this study was to document the way in which nitric oxide production is affected by allograft rejection, and to determine the significance of these changes. Enhanced nitric oxide synthesis may have a graft protective effect by inhibiting clonal expansion of immune cells targeting alloantigen. However, immunosuppressive agents have been shown to block NO production, raising the possibility that NO may modulate graft function and/or survival. The following hypotheses were tested; that acute cardiac allograft rejection is associated with a rise in NO production and an increase in iNOS expression, that conventional immunosuppressive agents reduce NO production by limiting iNOS expression, that an increase in substrate availability for nitric oxide synthase would increase NO production and decrease graft survival, and that L-NMMA, a competitive inhibitor of both constitutive and inducible isoforms would prolong graft survival.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Winlaw, D.S., Sprati, P.M., Macdonald, P.S. (1998). The Role of Nitric Oxide Production during Cardiac Allograft Rejection. In: Catravas, J.D., Callow, A.D., Ryan, U.S. (eds) Vascular Endothelium. NATO ASI Series, vol 294. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0133-0_42
Download citation
DOI: https://doi.org/10.1007/978-1-4899-0133-0_42
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-0135-4
Online ISBN: 978-1-4899-0133-0
eBook Packages: Springer Book Archive