Role of Endothelin in the Control of Peripheral Vascular Tone in Human Hypertension
Role of Endothelin in the Control of Peripheral Vascular Tone in Human Hypertension
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内皮素在控制人类高血压周围血管张力中的作用
DOI：
10.1023/a:1011400124060
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发表时间：
2001
影响因子：
4.6
通讯作者：
A. Salvetti
中科院分区：
文献类型：
--
作者：
S. Taddei;A. Virdis;L. Ghiadoni;I. Sudano;A. Magagna;A. Salvetti
内皮素是在不同血管组织（包括血管内皮）中产生的有效的21个氨基酸的血管收缩剂异肽。内皮素-1是内皮细胞产生的主要内皮素，可能是心血管系统中最重要的内皮素。内皮素-1通过称为ETA和ETB的特异性受体起作用，ETA仅存在于平滑肌细胞上并具有促进生长和介导收缩的功能，ETB位于平滑肌细胞上，在那里它们引起收缩，ETB位于内皮细胞上，通过产生内皮衍生的松弛因子一氧化氮诱导松弛。在生理条件下，内皮素-1给药分别在低浓度和高浓度下引起血管舒张和血管收缩。然而，混合的ETA/B受体拮抗剂的管理引起轻微的或不存在的血管舒张，表明肽的直接血管收缩作用可能被ETB诱导的NO依赖性血管舒张所掩盖。在原发性高血压患者中，与血压正常的受试者相比，外源性内皮素-1的活性增加、相似或降低，这取决于所考虑的血管区或给药方案。但是，尽管现有的证据并没有表明原发性高血压患者血浆内皮素-1水平升高，但ETA/B受体的同时拮抗作用导致高血压患者比正常血压受试者更大程度的血管舒张。此外，选择性ETB受体拮抗剂的施用引起血压正常受试者的血管收缩和原发性高血压患者的血管舒张。最后，混合ETA/B受体拮抗剂的血管舒张作用与NO的利用率呈负相关。综合这些发现表明，原发性高血压的特点是增加内皮素-1血管收缩张力。这种改变似乎取决于内皮ETB介导的NO产生的减少，而NO产生的减少归因于NO可用性受损。在这种情况下，内皮ETB诱导的血管舒张不再补偿由平滑肌细胞ETA和ETB受体介导的直接经典内皮素血管收缩作用。因此，内皮素-1可能参与原发性高血压或其并发症的发病机制，阻断该系统是治疗该疾病的一个迷人的新靶点。
Endothelins are potent 21 amino acid vasoconstrictor isopeptides produced in different vascular tissues, including vascular endothelium. Endothelin-1 is the main endothelin generated by the endothelium and probably the most important in the cardiovascular system. Endothelin-1 acts through specific receptors termed ETA, represented only on smooth muscle cells and having the function of growth promotion and mediating contractions, and ETB, located both on smooth muscle cells, where they evoke contractions, and on endothelial cells, inducing relaxation by production of the endothelium-derived relaxing factor nitric oxide. In physiological conditions endothelin-1 administration causes vasodilation and vasoconstriction at low and high concentrations, respectively. However, administration of mixed ETA/B receptor antagonists causes slight or absent vasodilation, indicating that the direct vasoconstrictor effect of the peptide is probably masked by ETB-induced NO-dependent vasodilation. In essential hypertensive patients, the activity of exogenous endothelin-1 is either increased, similar or decreased as compared to normotensive subjects, depending on which vascular district or scheme of administration is considered. But although available evidence does not indicate increased endothelin-1 plasma levels in patients with essential hypertension, simultaneous antagonism of ETA/B receptors causes a greater degree of vasodilation in hypertensives than in normotensive subjects. Moreover administration of a selective ETB receptor antagonist causes vasoconstriction in normotensive subjects and vasodilation in essential hypertensive patients. Finally, the vasodilating effect of a mixed ETA/B receptor antagonist is inversely related to NO availability. Taken together these findings suggest that essential hypertension is characterized by increased endothelin-1 vasoconstrictor tone. This alteration seems to be dependent on decreased endothelial ETB-mediated NO production attributable to impaired NO availability. In such conditions endothelial ETB-induced vasodilation no longer compensates for the direct classical endothelin vasoconstrictor effect mediated by smooth muscle cell ETA and ETB receptors. Therefore endothelin-1 could potentially be involved in the pathogenesis of essential hypertension or of its complications, and blockade of this system is a fascinating new target for therapeutic intervention in this disease.
影响因子：
37.8
作者：
Cardillo, C;Nambi, SS;Panza, JA
通讯作者：
Panza, JA
内皮细胞中非异肽选择性 ETB 受体的分子和功能表征。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Tsukahara,H;Ende,H;Magazine,HI;Bahou,WF;Goligorsky,MS
通讯作者：
Goligorsky,MS