Endothelial dysfunction in rat mesenteric artery after regional cardiac ischaemia-reperfusion

In most previous studies, ischaemia-reperfusion (I/R)-induced vascular injury referred to injury in the tissue or blood vessel that was directly subjected to I/R. However, less attention has been focused on remote vascular injury that might be caused by cardiac I/R. In the present study, we aimed to assess whether cardiac I/R could affect vasoconstriction and vasodilatation in mesenteric arteries from Sprague-Dawley rats. Left anterior descending coronary arteries from adult male Sprague-Dawley rats were occluded (60 min) and then reperfused (120 min). Changes in haemodynamic parameters indicated that this procedure caused evident cardiac dysfunction. In mesenteric arteries isolated from the animals, cardiac I/R significantly increased the maximal contractions in response to KCl, 5-hydroxytryptamine, phenylephrine and U46619 and decreased the maximal relaxation in response to acetylcholine, but not to sodium nitroprusside, compared with sham-operated animals. The nitric oxide synthase inhibitor L-NAME abolished differences of contractile responses to phenylephrine between sham-operated and I/R rats. The antioxidant N-acetyl-L-cysteine reversed the impairment of acetylcholine-stimulated vasodilatation induced by regional cardiac I/R. However, L-NAME caused a similar degree of inhibition of acetylcholine-stimulated relaxation in mesenteric arteries from sham-operated and I/R rats. Electron microscopy revealed that mesenteric arterial endothelial structure was degraded in the I/R group and that N-acetyl-L-cysteine treatment prevented this structural damage. In conclusion, regional cardiac I/R caused by transient occlusion and reperfusion of the left anterior descending coronary artery results in peripheral vascular endothelial dysfunction.