endothelium

Leukadherin-1 是 CD11b CD18 的变构激活剂，可增加 CD11b CD18 依赖性细胞对纤维蛋白原的粘附，减少白细胞运动和跨内皮迁移，具有抗炎作用。

Phellopterin 是一种分离自P. trifoliata 中的天然产物。它能够调节 Akt 和 PKC 通路，抑制 TNF-alpha 诱导的 VCAM-1 表达，进而减少单核细胞与内皮细胞的粘附。

E7820 (ER68203-00) 是具有口服活性芳香族磺酰胺衍生物，是一种血管生成抑制剂，可抑制内皮上整合素 α2 亚基的表达。它调节 α1，α2，α3 和 α5 整联素 mRNA 表达，具有抗血管生成和抗肿瘤活性。它抑制大鼠主动脉血管生成，IC50为 0.11 μg ml。

L-Nabe (H-Arg(NO2)-Obzl) 是一种有效的不可逆内皮依赖性舒张抑制剂。

CGP48369 是一种有效的血管紧张素 II 受体 (angiotensin II receptor) 拮抗剂，具有降血压作用，可增强自发性高血压大鼠冠状动脉的内皮依赖性松弛。

Pranidipine (OPC-13340) 是一种高效且长效的 1,4-二氢吡啶钙通道阻滞剂，可延长乙酰胆碱诱导的内皮松弛以及硝酸甘油诱导的内皮松弛，具有抗高血压作用。

SB-209670是一种选择性内皮素受体拮抗剂，能够抑制大鼠血管内皮和血管平滑肌中ET(B)受体的活性。

(S)-Coriolic acid (13(S)-HODE) 是一种重要的细胞内信号剂，是亚油酸与植物和哺乳动物脂氧合酶反应生成的，在各种生物系统中参与细胞增殖和分化。(S)-Coriolic acid 在 1 μM 左右时，它能抑制肿瘤细胞与血管内皮的粘附，能下调 IRGpIIb IIIa 受体的表达。(S)-Coriolic acid 是15-脂氧合酶 (15-LOX) 代谢产物，常作为内源性配体激活 PPARγ。(S)-Coriolic acid 诱导线粒体功能障碍 和气道上皮损伤。

Pheniramine maleate (Trimetose) 是一种具有抗组胺和血管扩张特性的烷基胺衍生物，可与组胺 H1 受体结合，从而抑制磷脂酶 A2 和内皮源性松弛因子一氧化氮的产生。

2-Ethylpyrazine 存在与烘焙后的咖啡豆中，是一种挥发性化合物 。2-Ethylpyrazine 通过内皮衍生的松弛因子的活动诱导血管舒张。2-Ethylpyrazine 通过内皮内皮NO 合酶的作用激活NO 合成。2-Ethylpyrazine 通过诱导NO 释放和增加外周血流量来诱导血管舒张。

Pyrimidine (Metadiazine) 是内源性代谢产物的一种。

(±)-Naringenin (Naringenine) 是一种天然的类黄酮。它通过激活肌细胞中 BKCa 通道发挥对内皮剥脱血管的舒张作用。

1,2,3,4,6-O-Pentagalloylglucose (Penta-O-galloyl-β-D-glucose) 存在于多种植物中，具有重要的药理作用。Pentagalloylglucose 表现出显著的抗狂犬病病毒 (RABV) 活性。

Bradykinin 是由激肽释放酶-激肽系统产生的活性肽。 它是炎症调节因子和神经调节因子，对几种血管和肾功能也有调节作用。

BORNESITOL是Hancornia speciosa的主要成分，这是一种具有证实的降压活性的药用植物。它被用作Hancornia speciosa心血管活性的活性标记。通过增加NO的产生或生物利用度，抑制ACE，以及依赖内皮和NO的血管舒张效应，BORNESITOL可以降低大鼠的血压。此外，BORNESITOL还被确定为quebrachitol的一种瞬时甲基化中间体。

Albifylline is a xanthine derivates with anti-asthmatic activity. Albifylline may cause a significant reduction of shock-induced leukocyte adhesions to the sinusoidal endothelium in the liver after hemorrhagic shock. Albifylline also improves microvascula

ICI 169369, a 5-HT2 5-HT1C antagonist, can evoke endothelium-dependent relaxation in rabbit aorta.

Arachidonic acid is metabolized in the vascular endothelium to epoxytrienoic acids (EETs or EpETrEs) by cytochrome P450 enzymes. The EETs are released in response to acetylcholine, bradykinin, arachidonic acid, or cyclic stretch. (±)14(15)-EET-SI is the methyl sulfonamide analog of 14(15)-EET. This substitution results in a metabolically more stable compound because it is not sensitive to β-oxidation or membrane esterification. (±)14(15)-EET-SI is equipotent to 14(15)-EET in vascular agonist activity as measured by relaxation of precontracted bovine coronary arteries. In addition, 14(15)-EET and the methyl sulfonamide analog both stimulate tyrosine phosphorylation and induce mitogenesis in renal epithelial cells.

Neuromedin U (NMU) is a neuropeptide first demonstrated to drive smooth muscle contraction.1Translated as a 174 amino acid propeptide, NMU is cleaved to different lengths in different animals. It has diverse receptor-mediated rolesin vivo, as it regulates feeding, vasoconstriction, nociception, and bone remodeling and contributes to obesity, cancer and septic shock.2,2NMU-25 is the active form of NMU in humans. It binds with high affinity to receptors on human left ventricle and coronary artery (KDs = 0.26 and 0.11 nM, respectively), eliciting endothelium-independent vasoconstriction.3NMU-25 also suppresses glucose-stimulated insulin secretion in human islets, and this effect is lost in NMU R165W mutants, resulting in early-onset obesity.4 1.Mitchell, J.D., Maguire, J.J., and Davenport, A.P.Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBritish Journal of Pharmacology15887-103(2009) 2.Greenwood, H.C., Bloom, S.R., and Murphy, K.G.Peptides and their potential role in the treatment of diabetes and obesityRev.Diabet.Stud.8(3)355-368(2011) 3.Mitchell, J.D., Maguire, J.J., Kuc, R.E., et al.Expression and vasoconstrictor function of anorexigenic peptides neuromedin U-25 and S in the human cardiovascular systemCardiovascular Research81353-361(2009) 4.Alfa, R.W., Park, S., Skelly, K.R., et al.Suppression of insulin production and secretion by a decretin hormoneCell Metabolism21(2)323-333(2015)

Angiotensin II is a hormone that plays an important role in regulating blood pressure. Elevated levels of angiotensin II are implicated in inducing and maintaining hypertension, and also in the development of atherosclerosis. Both of these effects are mediated by the angiotensin II type 1 (AT1) receptor. Losartan is a mammalian AT1 receptor antagonist with a Ki value of 5-20 nM. In humans, losartan effectively controls hypertension while protecting renal function. Nitric oxide (NO) causes vasodilation and also inhibits platelet and neutrophil aggregation in the endothelium. NO-losartan A possesses similar anti-hypertensive effects to losartan, with the addition of the vasodilating effects of NO release.

Cytochrome P450 metabolites of arachidonic acid, such as 11(12)-EpETrE and 14(15)-EpETrE have been identified as endothelium derived hyperpolarizing factors with vasodilator activity. Soluble epoxide hydrolase (sEH) catalyzes the conversion of EpETrEs to the corresponding DiHETrEs thereby diminishing their activity. Inhibitors of sEH may therefore have clinical utility for treating hypertension and systemic inflammation. S-NEPC is a colorimetric substrate used to measure sEH activity. It also is a substrate for Glutathione S-transferase, microsomal epoxide hydrolase and porcine liver carboxylesterase. Hydrolysis of S-NEPC by sEH yields 4-nitrophenol which can be quantified spectrophotometrically at 405 nm. S-NEPC is adaptable for use in 96-well microwell plate readers.

Epoxyeicosatrienoic acids (EETs), such as 11(12)-EET and 14(15)-EET, are cytochrome P450 metabolites of arachidonic acid that have been identified as endothelium-derived hyperpolarizing factors with vasodilator activity. 14,15-EE-5(Z)-E is a structural analog of 14,15-epoxyeicosatrienoic acids (14,15-EET) that antagonizes EET-induced relaxation of vascular smooth muscle. Relaxation of U46619-constricted bovine arteries by 14,15-EET could be inhibited approximately 80% by 14,15-EE-5(Z)-E at a concentration of 10 μM. 14,15-EE-5(Z)-E does not appear to antagonize nitric oxide- or iloprost-mediated vascular relaxation.

Epoxyeicosatrienoic acids (EETs), such as 11(12)-EET and 14(15)-EET, are cytochrome P450 metabolites of arachidonic acid that have been identified as endothelium-derived hyperpolarizing factors with vasodilator activity. 14,15-EE-8(Z)-E is a structural analog of 14(15)-EET that demonstrates potent vasodilator agonist activity in bovine coronary arteries similar to that of 14(15)-EET.

EDHF (endothelium-derived hyperpolarizing factor) is an unidentified mediator released from vascular endothelial cells in response to acetylcholine and bradykinin which is distinct from the NOS- (nitric oxide) and COX-derived (prostacyclin) vasodilators.[1],[2]Cytochrome P450 (CYP450) metabolism of polyunsaturated fatty acids produces epoxides such as (±)14(15)-EET which are prime candidates for the actual active mediator.[3] However, the CYP450 metabolites of eicosapentaenoic acid and docosahexaenoic acid have been little studied relative to arachidonate epoxygenase metabolites. (±)16(17)-EpDPA is the DHA homolog of (±)14(15)-EpETrE, derived via epoxidation of the 16,17-double bond of DHA. The EDHF activity of (±)16(17)-EpDPA has not yet been determined. The epoxygenase metabolites of DHA have also been detected in a mouse inflammation model.[4]