准位于面腹中枢髓中的胺H4受体,以缓解高血压
Ying Shi1, Yang-Xun Zhang1, Jun-Yi Chen1
1State Key Laboratory of Pharmaceutical Biotechnology, National Resource Center for Mutant Mice, Department of Anesthesiology, Nanjing Drum Tower Hospital, Institute for Brain Sciences, and Department of Physiology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|September 29, 2025
概括
研究人员发现大脑干中的组胺H4受体 (H4R) 调节血压. 激活这种受体会降低血压,为高血压治疗提供了一个潜在的新点.
科学领域:
- 神经科学是一个神经科学.
- 心血管研究研究心血管研究
- 药理学 药理学是指药理学的学科.
背景情况:
- 耐药性高血压通常与来自大脑的交感神经系统活动增加有关.
- 目前对高血压的中央治疗目标仍然有限.
- 基因素H4受体 (H4R) 是最近发现的基因素受体,在中央心血管调节中具有尚未探索的作用.
研究的目的:
- 研究组胺H4受体 (H4R) 在中央心血管调节中的作用.
- 探索H4R作为高血压的潜在治疗点.
主要方法:
- 对人类大脑单核RNA测序数据和大鼠大脑RNAscope测试进行分析,以确定H4R表达.
- 在大鼠的正面腹中中枢骨髓 (RVMM) 中,对基因组特异性 afferents 的光遗传刺激.
- 在自发高血压和压力诱导高血压的老鼠模型中,注射H4R激动剂.
主要成果:
- H4R在RVMM中得到一致的表达,RVMM是对同情心血管控制的关键中心.
- 通过H4R,RVMM基因组活性因子的光激活诱导了血压降低和心率降低.
- H4R激活激发GABAergic预交感神经元,通过暂时受体潜在化物1 (TRPV1) 进行介导.
- 在高血压的老鼠模型中,鼻内H4R激动剂的使用导致持续的血压降低.
结论:
- 在RVMM中的组胺H4受体发挥了抗高血压作用.
- RVMM H4R代表了管理高血压的有希望的中央治疗点.
相关概念视频
01:28Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
944
Histamine H2 receptors, which are intricately located on the basolateral membrane of parietal cells, play a crucial role in modulating gastric acid secretion. When released from enterochromaffin-like cells, histamine engages H2 receptors, initiating the cyclic AMP (cAMP) pathway. In this pathway, adenylyl cyclase converts ATP into cAMP, elevating intracellular cAMP levels. The activation of protein kinase A follows, stimulating the proton pump. This stimulation prompts the secretion of hydrogen...
944
01:23Antihypertensive Drugs: Vasodilators
2.0K
Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
2.0K
01:17Antihypertensive Drugs: Action of β1 Blockers
1.9K
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,...
1.9K
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
936
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
936
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
2.5K
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...
2.5K
01:30Adrenergic Agonists: Therapeutic Uses
1.7K
Adrenergic agonists have diverse therapeutic uses across various medical conditions and emergencies.
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and...
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and...
1.7K