在具有脱氧皮质酸盐-盐高血压的内多林-B受体缺乏的老鼠中,过度的血管和病理
Y Matsumura1, T Kuro, Y Kobayashi
1Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan.
Circulation
|November 30, 2000
概括
内甲素 (ET) -B受体缺乏症加剧了脱氧皮质乙酸盐 (DOCA) -盐的高血压和组织损伤. 通过ET(B) 介导的作用具有保护作用,而ET(A) 受体阻塞可以防止高血压和损伤.
科学领域:
- 心血管科学 心血管科学
- 脏生理学 脏生理学
- 内分泌学 在内分泌学.
背景情况:
- 恩多林 (ET) - 1与脱氧皮质乙酸盐 (DOCA) 盐引起的高血压有关.
- 在这种高血压模型,心血管缩和损伤中,ET(B) 受体的作用被研究使用具有ET(B) 受体基因缺失的斑点致死性 (sl) 鼠.
研究的目的:
- 评估ET(B) 受体在DOCA盐诱导的高血压,心血管缩和损伤中的病理作用.
- 在此高血压模型中评估ET(B) 受体功能的保护性或有害性.
主要方法:
- 使用了斑点致死性 (sl) 鼠,在ET(B) 受体基因中存在遗传缺失.
- 开发出在特定组织中表达ETB受体的DssH-ET(B) sl/sl大鼠,以确保在成年后的生存.
- 对同卵性 (sl/sl) 和野生型转基因大鼠进行DOCA盐治疗.
- 使用ET(A) 受体对抗剂 (ABT-627) 进行了慢性治疗.
主要成果:
- 与野生型大鼠相比,同卵性SL/SL大鼠表现出较早和更严重的缩血压增加,功能障碍和组织学损伤.
- 血管缩在同卵性老鼠中更为明显.
- 在两组中,ET(A) 受体抗剂治疗 (ABT-627) 完全抑制了高血压,并显著改善了和血管损伤.
- 用DOCA盐治疗导致同卵性老鼠的ET-1水平增加,这些水平被ABT-627.7正常化.
结论:
- 通过ET(B) 介导的作用对DOCA盐诱导的高血压和相关组织损伤有保护作用.
- 增强的ET-1产生和ET ((A) 介导的作用有助于增加ET ((B) 受体缺乏的老鼠对DOCA盐高血压的敏感性.
相关概念视频
Hypertension and Regulation of Blood Pressure
Hypertension, the most common cardiovascular disease, is diagnosed through repeated measurements of elevated blood pressure. Its risks, including damage to the kidney, heart, and brain, are directly proportional to blood pressure levels. Starting from 115/75 mm Hg, the risk of cardiovascular disease doubles with each increment of 20/10 mm Hg. The diagnosis relies on blood pressure measurements, not on patient symptoms, as hypertension is often asymptomatic until end-organ damage is imminent or...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
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...
Antihypertensive Drugs: Angiotensin II Receptor Blockers
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...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
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...
Heart Failure II: Pathophysiology
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
Hypertension II: Pathophysiology
Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...


