阿尔多斯特增强了血管光滑肌细胞中血管素II诱导的信号传递
Istvan Mazak1, Anette Fiebeler, Dominik N Muller
1Medical Faculty of the Charité, Franz Volhard Clinic, HELIOS Klinikum-Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Circulation
|May 26, 2004
概括
阿尔多斯特在血管细胞中增强了Ang II诱导的信号传递. 矿物质皮质类受体阻断抑制了这些效应,解释了对抗血管素II诱导的损伤的体内益处.
科学领域:
- 心血管生物学 心血管生物学
- 脏生理学 脏生理学
- 细胞信号传递 细胞信号传递
背景情况:
- 矿物质皮质类受体 (MR) 的阻断减轻了血管激素II (Ang II) 诱导的器官损伤.
- 在这种情况下,Ang II和阿尔多素 (Ald) 之间的相互作用尚不清楚.
研究的目的:
- 研究Ang II和Ald对血管光滑肌细胞 (VSMC) 信号传递的联合作用.
- 阐明反应性氧物种 (ROS),MR和表皮生长因子受体 (EGFR) 在Ang II和Ald信号传递中的作用.
主要方法:
- 利用西方抹黑和共聚焦显微镜来评估VSMC中的细胞外信号调节激酶 (ERK) 和c-Jun N-终端激酶 (JNK) 酸化.
- 采用氧基吸收剂,EGFR抗剂 (AG1478),以及MR阻断剂 (螺旋).
主要成果:
- 二和阿尔德独立诱导ERK1/2和JNK酸化;它们的组合显示出强化作用.
- ROS,MR和EGFR与Ang II和Ald.激活的信号通路有关.
- 斯皮罗诺拉克取消了Ang II诱导的ROS生成,EGFR转活和ERK1/2酸化.
结论:
- 阿尔多斯特增强了Ang II诱导的ERK1/2和JNK在VSMC中的酸化.
- ROS,MR和EGFR是早期Ang II和Ald信号的关键媒介.
- 这些发现提供了体外机械洞察力,以了解MR阻断对抗Ang II诱导的末端器官损伤的体内疗效.
相关概念视频
Adrenergic Receptors: ɑ Subtype
2.7K
Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
2.7K
Antihypertensive Drugs: Action of β1 Blockers
2.2K
β1-receptors are primarily located in the heart and kidneys. In cardiac myocytes, these receptors interact with neurotransmitters released by the sympathetic nervous system during heightened activity or danger. As a result, β1-receptors get activated, initiating a series of biochemical processes. Excessive activation of beta receptors due to chronic stress can abnormally increase heart rate and contractility, resulting in high blood pressure or hypertension. To counteract this,...
2.2K
Antihypertensive Drugs: Action of Calcium Channel Blockers
2.4K
Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
2.4K
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
2.7K
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
2.7K
Antihypertensive Drugs: Angiotensin II Receptor Blockers
2.9K
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
2.9K
Autoregulation of Blood Flow
10.0K
Autoregulation mechanisms are characterized by their inherent capacity for self-regulation without necessitating specific nervous stimulation or endocrine control. These mechanisms facilitate the adjustment of blood flow and, therefore, perfusion specific to each tissue region. This self-regulation encompasses chemical signals and myogenic controls.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation....
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation....
10.0K


