title: Increased levels of circulating nitrates and impaired endothelium-mediated vasodilation suggest multiple roles of nitric oxide during acute rejection of pulmonary allografts.
abstract: Experiments were designed to determine whether changes in pulmonary artery function could be reduced by treatment with a lipid peroxidation inhibitor (H 290/51) during acute rejection of pulmonary allografts. Single lung transplantation was performed in three groups of dogs: group 1 was maintained on immunosuppression for 8 days after operation (immunosuppressed, n = 5); in group 2, immunosuppression was discontinued on postoperative day 5, so that rejection occurred on postoperative day 8 (rejecting, n = 6); in group 3, immunosuppression was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 (25 mg/kg) was given perorally for 3 days (rejecting + H 290/51, n = 6). Plasma nitric oxide (NO(x)) was measured by use of chemoluminescence. On postoperative day 8 rejection was observed in groups 2 and 3. Contractions to angiotensin I and endothelium-dependent relaxations to adenosine diphosphate were reduced in pulmonary arteries from rejecting lungs. Responses of rings from dogs treated with H 290/51 were similar to those from rejecting lungs. Rejection did not alter relaxations to exogenous nitric oxide. However, plasma levels of NO(x) increased significantly during rejection independently of treatment with H 290/51. Results of this study confirm that endothelium-dependent relaxation of pulmonary arteries is reduced during acute rejection of lung allografts. The result extends these observations to suggest that treatment with a lipid peroxidation inhibitor neither protects the pulmonary artery function nor affects levels of circulating NO(x). Therefore mechanisms other than lipid peroxidation participate in vascular changes associated with allograft rejection.
authors.affiliation: Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wiklund
authors.forename: D H
authors.initials: DH
authors.lastname: Lewis
authors.forename: P O
authors.initials: PO
authors.lastname: Sjöquist
authors.forename: F
authors.initials: F
authors.lastname: Nilsson
authors.forename: H
authors.initials: H
authors.lastname: Tazelaar
authors.forename: V M
authors.initials: VM
authors.lastname: Miller
authors.forename: C G
authors.initials: CG
authors.lastname: McGregor
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects*; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood / Q000276:immunology*; D011651:Pulmonary Artery / Q000187:drug effects*
chemical_list: D000975:Antioxidants; C088233:H290-51; D007166:Immunosuppressive Agents; D007211:Indoles; D009569:Nitric Oxide