Increased levels of circulating nitrates and impaired endothelium-mediated vasodilation suggest multiple roles of nitric oxide during acute rejection of pulmonary allografts.
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.
Wiklund
L
L
Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
Lewis
D H
DH
Sjöquist
P O
PO
Nilsson
F
F
Tazelaar
H
H
Miller
V M
VM
McGregor
C G
CG
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*
D000975:Antioxidants; C088233:H290-51; D007166:Immunosuppressive Agents; D007211:Indoles; D009569:Nitric Oxide