Adenosine is a ubiquitous endogenous nucleoside or autacoid that affects the cardiovascular system through the activation of four G-protein coupled receptors: adenosine A₁ receptor (A₁AR), adenosine A_2A receptor (A_2AAR), adenosine A_2B receptor (A_2BAR), and adenosine A₃ receptor (A₃AR). With the rapid generation of this nucleoside from cellular metabolism and the widespread distribution of its four G-protein coupled receptors in almost all organs and tissues of the body, this autacoid induces multiple physiological as well as pathological effects, not only regulating the cardiovascular system but also the central nervous system, peripheral vascular system, and immune system. Mounting evidence shows the role of CYP450-enzymes in cardiovascular physiology and pathology, and the genetic polymorphisms in CYP450s can increase susceptibility to cardiovascular diseases (CVDs). One of the most important physiological roles of CYP450-epoxygenases (CYP450-2C & CYP2J2) is the metabolism of arachidonic acid (AA) and linoleic acid (LA) into epoxyeicosatrienoic acids (EETs) and epoxyoctadecaenoic acid (EpOMEs) which generally involve in vasodilation. Like an increase in coronary reactive hyperemia (CRH), an increase in anti-inflammation, and cardioprotective effects. Moreover, the genetic polymorphisms in CYP450-epoxygenases will change the beneficial cardiovascular effects of metabolites or oxylipins into detrimental effects. The soluble epoxide hydrolase (sEH) is another crucial enzyme ubiquitously expressed in all living organisms and almost all organs and tissues. However, in contrast to CYP450-epoxygenases, sEH converts EETs into dihydroxyeicosatrienoic acid (DHETs), EpOMEs into dihydroxyoctadecaenoic acid (DiHOMEs), and others and reverses the beneficial effects of epoxy-fatty acids leading to vasoconstriction, reducing CRH, increase in pro-inflammation, increase in pro-thrombotic and become less cardioprotective. Therefore, polymorphisms in the sEH gene (Ephx2) cause the enzyme to become overactive, making it more vulnerable to CVDs, including hypertension. Besides the sEH, ω-hydroxylases (CYP450-4A11 & CYP450-4F2) derived metabolites from AA, ω terminal-hydroxyeicosatetraenoic acids (19-, 20-HETE), lipoxygenase-derived mid-chain hydroxyeicosatetraenoic acids (5-, 11-, 12-, 15-HETEs), and the cyclooxygenase-derived prostanoids (prostaglandins: PGD₂, PGF_2α; thromboxane: Txs, oxylipins) are involved in vasoconstriction, hypertension, reduction in CRH, pro-inflammation and cardiac toxicity. Interestingly, the interactions of adenosine receptors (A_2AAR, A₁AR) with CYP450-epoxygenases, ω-hydroxylases, sEH, and their derived metabolites or oxygenated polyunsaturated fatty acids (PUFAs or oxylipins) is shown in the regulation of the cardiovascular functions. In addition, much evidence demonstrates polymorphisms in CYP450-epoxygenases, ω-hydroxylases, and sEH genes (Ephx2) and adenosine receptor genes (ADORA1 & ADORA2) in the human population with the susceptibility to CVDs, including hypertension. CVDs are the number one cause of death globally, coronary artery disease (CAD) was the leading cause of death in the US in 2019, and hypertension is one of the most potent causes of CVDs. This review summarizes the articles related to the crosstalk between adenosine receptors and CYP450-derived oxylipins in vascular, including the CRH response in regular salt-diet fed and high salt-diet fed mice with the correlation of heart perfusate/plasma oxylipins. By using A_2AAR^−/−, A₁AR^−/−, eNOS^−/−, sEH^−/− or Ephx2^−/−, vascular sEH-overexpressed (Tie2-sEH Tr), vascular CYP2J2-overexpressed (Tie2-CYP2J2 Tr), and wild-type (WT) mice. This review article also summarizes the role of pro-and anti-inflammatory oxylipins in cardiovascular function/dysfunction in mice and humans. Therefore, more studies are needed better to understand the crosstalk between the adenosine receptors and eicosanoids to develop diagnostic and therapeutic tools by using plasma oxylipins profiles in CVDs, including hypertensive cases in the future.

腺苷是一种普遍存在的内源性核苷或内分泌素，通过激活四种 G 蛋白偶联受体影响心血管系统：腺苷 A ₁受体 (A ₁ AR)、腺苷 A _2A受体 (A _2A AR)、腺苷 A _2B受体 (A _2B AR）和腺苷 A ₃受体（A ₃应收账款）。随着这种核苷在细胞代谢中的快速生成及其四种 G 蛋白偶联受体在身体几乎所有器官和组织中的广泛分布，这种内分泌素会引起多种生理和病理作用，不仅调节心血管系统，而且还有中枢神经系统、外周血管系统和免疫系统。越来越多的证据表明 CYP450 酶在心血管生理学和病理学中的作用，并且 CYP450 中的遗传多态性可以增加心血管疾病 (CVD) 的易感性。CYP450-环氧合酶 (CYP450-2C & CYP2J2) 是花生四烯酸 (AA) 和亚油酸 (LA) 代谢成环氧二十碳三烯酸 (EET) 和环氧十八碳烯酸 (EpOME)，通常参与血管舒张。就像冠状动脉反应性充血 (CRH) 的增加、抗炎作用的增加和心脏保护作用一样。此外，CYP450-环氧合酶的遗传多态性会将代谢物或氧磷脂的有益心血管作用转变为有害作用。可溶性环氧化物水解酶 (sEH) 是另一种在所有生物体和几乎所有器官和组织中普遍表达的重要酶。然而，与 CYP450-环氧合酶相反，sEH 将 EET 转化为二羟基二十碳三烯酸 (DHET)，将 EpOME 转化为二羟基十八碳烯酸 (DiHOME)，和其他并逆转环氧脂肪酸导致血管收缩的有益作用，减少 CRH，增加促炎症，增加促血栓形成并降低心脏保护作用。因此，sEH 基因 (Ephx2) 的多态性导致该酶变得过度活跃，使其更容易受到 CVD 的影响，包括高血压。除了 sEH，ω-羟化酶（CYP450-4A11 和 CYP450-4F2）衍生自 AA、ω 末端羟基二十碳四烯酸（19-、20-HETE）、脂肪氧化酶衍生的中链羟基二十碳四烯酸（5-、11-、 12-, 15-HETEs), 和环氧合酶衍生的前列腺素类 (前列腺素: PGD 使其更容易患上心血管疾病，包括高血压。除了 sEH，ω-羟化酶（CYP450-4A11 和 CYP450-4F2）衍生自 AA、ω 末端羟基二十碳四烯酸（19-、20-HETE）、脂肪氧化酶衍生的中链羟基二十碳四烯酸（5-、11-、 12-, 15-HETEs), 和环氧合酶衍生的前列腺素类 (前列腺素: PGD 使其更容易患上心血管疾病，包括高血压。除了 sEH，ω-羟化酶（CYP450-4A11 和 CYP450-4F2）衍生自 AA、ω 末端羟基二十碳四烯酸（19-、20-HETE）、脂肪氧化酶衍生的中链羟基二十碳四烯酸（5-、11-、 12-, 15-HETEs), 和环氧合酶衍生的前列腺素类 (前列腺素: PGD₂、生长_因子2α；血栓烷：Txs，oxylipins) 参与血管收缩、高血压、CRH 减少、促炎症和心脏毒性。有趣的是，腺苷受体 (A _2A AR, A ₁AR) 与 CYP450-环氧合酶、ω-羟化酶、sEH 及其衍生代谢物或含氧多不饱和脂肪酸（PUFA 或氧磷脂）一起调节心血管功能。此外，许多证据表明 CYP450-环氧合酶、ω-羟化酶和 sEH 基因 (Ephx2) 和腺苷受体基因（ADORA1 和 ADORA2）在易患 CVD（包括高血压）的人群中存在多态性。CVD 是全球第一大死因，冠状动脉疾病 (CAD) 是 2019 年美国的首要死因，而高血压是导致 CVD 的最主要原因之一。本综述总结了血管中腺苷受体与 CYP450 衍生的氧磷脂之间串扰相关的文章，包括常规盐饮食喂养和高盐饮食喂养小鼠的 CRH 反应与心脏灌注液/血浆氧脂的相关性。通过使用_2A AR ^-/-，A ₁ AR ^-/-，eNOS ^-/-， sEH ^-/-或 Ephx2 ^-/-，血管 sEH 过表达（Tie2-sEH Tr），血管 CYP2J2 过表达（Tie2-CYP2J2 Tr），和野生型 (WT) 小鼠。这篇评论文章还总结了促炎和抗炎性氧磷脂在小鼠和人类心血管功能/功能障碍中的作用。因此，需要更多的研究来更好地了解腺苷受体和类花生酸之间的串扰，以通过使用 CVD 中的血浆氧磷脂谱来开发诊断和治疗工具，包括未来的高血压病例。