Ischaemia-reperfusion injury impairs the nitric oxide/soluble guanylate cyclase/cyclic
guanosine monophosphate (cGMP) signalling pathway and leads to vascular dysfunction.
We assessed the hypothesis that the soluble guanylate cyclase activator cinaciguat
would protect the vascular graft against ischaemia-reperfusion injury.In the treatment
groups, rats (n = 8/group) were pretreated with either intravenous saline or intravenous
cinaciguat (10 mg/kg) 2 h before an aortic transplant. Aortic grafts were stored for
2 h in saline and transplanted into the abdominal aorta of the recipients. Two hours
after the transplant, the grafts were harvested and mounted in an organ bath. Vascular
function of the grafts was investigated in the organ bath. Terminal deoxynucleotidyl
transferase dUTP nick end labelling, cluster of differentiation 31, caspase-3, endothelial
nitric oxide synthase, cGMP, nitrotyrosine and vascular cell adhesion molecule 1 immunochemical
reactions were also investigated.Pretreatment with cinaciguat significantly improved
endothelium-dependent maximal relaxation 2 h after reperfusion compared with the saline
group (maximal relaxation control: 96.5 ± 1%, saline: 40.4 ± 3% vs cinaciguat: 54.7
± 2%; P < 0.05). Pretreatment with cinaciguat significantly reduced DNA fragmentation
and nitro-oxidative stress; decreased the caspase-3 and vascular cell adhesion molecule
1 scores; and increased endothelial nitric oxide synthase, cGMP and cluster of differentiation
31 scores.Our results demonstrated that enhancement of cGMP signalling by pharmacological
activation of the soluble guanylate cyclase activator cinaciguat might represent a
beneficial therapy for treating endothelial dysfunction of arterial bypass graft during
cardiac surgery.
