Neuronal nitric oxide synthase-derived hydrogen peroxide effect in grafts used in human coronary bypass surgery

Abstract

Recently, HO has been identified as the endothelium-dependent hyperpolarizing factor (EDHF), which mediates flow-induced dilation in human coronary arteries. Neuronal nitric oxide synthase (nNOS) is expressed in the cardiovascular system and, besides NO, generates HO The role of nNOS-derived HO in human vessels is so far unknown. The present study was aimed at investigating the relevance of nNOS/HO signaling in the human internal mammary artery (IMA) and saphenous vein (SV), the major conduits used in coronary artery bypass grafting. In the IMA, but not in the SV, ACh (acetylcholine)-induced vasodilatation was decreased by selective nNOS inhibition with TRIM or Inhibitor 1, and by catalase, which specifically decomposes HO Superoxide dismutase (SOD), which generates HO from superoxide, decreased the vasodilator effect of ACh on SV. In the IMA, SOD diminished phenylephrine-induced contraction in endothelium-containing, but not in endothelium-denuded vessels. Importantly, while exogenous HO produced vasodilatation in IMA, it constricted SV. ACh increased HO production in both sets of vessels. In the IMA, the increase in HO was inhibited by catalase and nNOS blockade. In SV, HO production was abolished by catalase and reduced by nNOS inhibition. Immunofluorescence experiments showed the presence of nNOS in the vascular endothelium and smooth muscle cells of both the IMA and SV. Together, our results clearly show that HO induced endothelium-dependent vascular relaxation in the IMA, whereas, in the SV, HO was a vasoconstrictor. Thus, HO produced in the coronary circulation may contribute to the susceptibility to accelerated atherosclerosis and progressive failure of the SV used as autogenous graft in coronary bypass surgery.

Mitochondrial depolarization stimulates vascular repair‐relevant functions of CD34+ cells via reactive oxygen species‐induced nitric oxide generation

“…A recent study by Endlich et al . () provided pharmacological evidence for the generation of H 2 O 2 by nNOS. Another notable study by Ihara et al .…”

Venous endothelial function in cardiovascular disease

“…Interestingly, a study evaluating human internal mammary artery and saphenous veins undergoing coronary artery bypass grafting, showed that H 2 O 2 – considered an endogenous EDH mechanism in the coronary bed – induced different responses in arteries and veins [ 108 ]. While H 2 O 2 was produced by the nNOS on the internal mammary artery, resulting in vasodilation after acetylcholine stimuli; in saphenous veins H 2 O 2 was generated by nNOS and by COX, inducing venoconstriction [ 108 ].…”

The influence of grafted coronary arteries on vascular conduits

“…Последний играет важную роль в регуляции взаимодействия клеток между собой и с экстрацеллюлярным матриксом и способен вовлекать в процесс ремоделирования сосудистой стенки адвентициальные миофибробласт-подобные клетки. Авторы указанного исследования продемонстрировали, что посредством этого белка изменения изначально происходят в адвентиции, в частности в зоне vasa vasorum, позже в медиальном слое [4].…”

“…Так, в литературе неоднократно описано, что некоторые кондуиты, в частности внутренняя грудная артерия, оказывают особое кардиопротективное действие. В силу способности продуцировать ряд веществ, таких как оксид азота, простациклин и эндотелиальный гиперполяризующий фактор [2][3][4], эти кондуиты способствуют формированию особой регуляции сосудистой стенки КА [2,5]. В целом можно предполагать о создании не только новых гемодинамических условий для перфузии коронарного русла, но и, по всей вероятности, нового иммунно-биохимического и даже молекулярно-генетического комплекса факторов [1,6].…”