一氧化氮(Nitric Oxide,NO)是人们熟知的无机小分子化合物,但长期以来对它真正的生理功能却知之甚少。近年来,随着血管内皮衍生舒张因子(Endothelium-Derived Relaxing Factor,EDRF)的化学本质就是 NO 理论的提出,对 NO 在心血管系统中...一氧化氮(Nitric Oxide,NO)是人们熟知的无机小分子化合物,但长期以来对它真正的生理功能却知之甚少。近年来,随着血管内皮衍生舒张因子(Endothelium-Derived Relaxing Factor,EDRF)的化学本质就是 NO 理论的提出,对 NO 在心血管系统中的重要生物学作用已取得普遍共识。现认为 NO 是一种基本的细胞内介质,在高血压等心血管疾病中起着自体活性物的作用。这一发现加深了对高血压病的认识。展开更多
In the last thirty years, it became obvious that the endothelium mediates relaxations of the underlying vas- cular smooth muscle cells by releasing endothelium-derived relaxing factors （EDtlF） , which results in end...In the last thirty years, it became obvious that the endothelium mediates relaxations of the underlying vas- cular smooth muscle cells by releasing endothelium-derived relaxing factors （EDtlF） , which results in endothelium- dependent vasodilatations. The best characterized EDRF is nitric oxide （NO） formed from 1-arginine by the consti- tutive endothelial NO synthase （eNOS）. NO diffuses to the vascular smooth muscle where it stimulates soluble gua- nylyl cyclase with, under normal conditions, the resulting production of cyclic C, MP. The release of NO from the endothelium can be mediated by both pertussis toxin-sensitive C,i- （ e. g. α2-adrenergic agonists, serotonin） and in- sensitive C,q- （adenosine diphosphate, bradykinin） proteins. The ability of the endothelial cell to release relaxing factors can be up-regulated by estrogens, increased flow, exercise, diet （ ω3-unsaturated fatty acids, polyphenols） and antioxidants, and down-regulated by oxidative stress and increased presence of oxidized low density lipoproteins （LDL）. It is reduced chronically by aging, smoking, environmental pollution and in hypertension and diabetes. Following injury or apoptotic death, the endothelium regenerates. However, in regenerated endothelial cells, there is an early selective loss of the pertussis-toxin sensitive mechanisms of EDRF-release. The reduced release of NO resulting from the endothelial dysfunction in regenerated areas sets the stage for the occurrence of vasospasm and thrombosis as well as it permits the inflammatory response leading to atherosclerosis. In addition to causing less di- rect relaxation of the underlying vascular smooth muscle, reduced release of NO also unleashes the production of vasoconstrictor prostanoids and/or endothelin-1. Blunted endothelium-dependent relaxations can also be caused by unresponsiveness of the vascular smooth muscle to NO. Finally, in coronary arteries hypoxia causes an acute aug- mentation of vasoconstrictor responses that is dependent on the presence of NO. This hypoxic effect is due to the bi- ased activity of soluble guanylyl cyclase which results in the synthesis of inosine 3＇ ,5＇ -cyclic monophosphate （ cI- MP）. Since hypoxia is implicated in exaggerated vasoconstriction in the pathogenesis of coronary artery disease, myocardial infarction, hypertension and stroke, the understanding of the role of this non-canonical cyclic nucleotide may help identifying novel therapeutic targets for certain cardiovascular disorders.展开更多
文摘一氧化氮(Nitric Oxide,NO)是人们熟知的无机小分子化合物,但长期以来对它真正的生理功能却知之甚少。近年来,随着血管内皮衍生舒张因子(Endothelium-Derived Relaxing Factor,EDRF)的化学本质就是 NO 理论的提出,对 NO 在心血管系统中的重要生物学作用已取得普遍共识。现认为 NO 是一种基本的细胞内介质,在高血压等心血管疾病中起着自体活性物的作用。这一发现加深了对高血压病的认识。
文摘In the last thirty years, it became obvious that the endothelium mediates relaxations of the underlying vas- cular smooth muscle cells by releasing endothelium-derived relaxing factors （EDtlF） , which results in endothelium- dependent vasodilatations. The best characterized EDRF is nitric oxide （NO） formed from 1-arginine by the consti- tutive endothelial NO synthase （eNOS）. NO diffuses to the vascular smooth muscle where it stimulates soluble gua- nylyl cyclase with, under normal conditions, the resulting production of cyclic C, MP. The release of NO from the endothelium can be mediated by both pertussis toxin-sensitive C,i- （ e. g. α2-adrenergic agonists, serotonin） and in- sensitive C,q- （adenosine diphosphate, bradykinin） proteins. The ability of the endothelial cell to release relaxing factors can be up-regulated by estrogens, increased flow, exercise, diet （ ω3-unsaturated fatty acids, polyphenols） and antioxidants, and down-regulated by oxidative stress and increased presence of oxidized low density lipoproteins （LDL）. It is reduced chronically by aging, smoking, environmental pollution and in hypertension and diabetes. Following injury or apoptotic death, the endothelium regenerates. However, in regenerated endothelial cells, there is an early selective loss of the pertussis-toxin sensitive mechanisms of EDRF-release. The reduced release of NO resulting from the endothelial dysfunction in regenerated areas sets the stage for the occurrence of vasospasm and thrombosis as well as it permits the inflammatory response leading to atherosclerosis. In addition to causing less di- rect relaxation of the underlying vascular smooth muscle, reduced release of NO also unleashes the production of vasoconstrictor prostanoids and/or endothelin-1. Blunted endothelium-dependent relaxations can also be caused by unresponsiveness of the vascular smooth muscle to NO. Finally, in coronary arteries hypoxia causes an acute aug- mentation of vasoconstrictor responses that is dependent on the presence of NO. This hypoxic effect is due to the bi- ased activity of soluble guanylyl cyclase which results in the synthesis of inosine 3＇ ,5＇ -cyclic monophosphate （ cI- MP）. Since hypoxia is implicated in exaggerated vasoconstriction in the pathogenesis of coronary artery disease, myocardial infarction, hypertension and stroke, the understanding of the role of this non-canonical cyclic nucleotide may help identifying novel therapeutic targets for certain cardiovascular disorders.
