循环氧化酶-2抑制的程度调节了血压反应的反应
Katherine N Theken1,2, Soumita Ghosh1, Carsten Skarke1,3
1Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia. (K.N.T., S.G., C.S., S.F., N.F.L., D.S., G.R.G., G.A.F., T.G.).
Hypertension (Dallas, Tex. : 1979)
|December 29, 2025
概括
纳普洛克森比塞莱科西布更有效地抑制循环氧化酶-2 (COX-2),导致血压增加. 这凸显了在评估非类固醇抗炎药物心血管风险时考虑药物效能的重要性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 心血管研究研究心血管研究
- 药品安全 药品安全
背景情况:
- 之前对非类固醇抗炎药物 (NSAID) 和心血管风险的临床试验没有标准化用于等效循环氧化酶 (COX) 抑制的剂量.
- 在NSAID中不同程度的COX-2抑制可能会影响其心血管安全概况.
研究的目的:
- 为了比较切莱可西布和纳普罗森之间的循环氧化酶 (COX) 向抑制和血压 (BP) 响应.
- 调查COX-2抑制与血压变化之间的关系.
主要方法:
- 这是一项双盲交叉研究,涉及16名健康参与者,他们接受了selecoxib (200 mg/d),naproxen (500 mg/d) 或安慰剂治疗7天.
- 使用ex vivo全血测定和in vivo尿中代谢物量化 (COX-1和COX-2) 来评估COX抑制.
- 在最后的剂量间隔期间,随行血压被监测.
主要成果:
- 这两种NSAID都抑制了COX-2活性,但纳普罗森的抑制显著地更大 (62.9%),而塞莱科克西布 (35.7%).
- 纳普洛克森也显示出更大的抑制体内前环素的形成 (COX-2标志物) 比celecoxib.
- 纳普洛克森显著增加了平均动脉,静脉缩和静脉缩血压,与塞莱科克西布和安慰剂相比,血压增加与COX-2抑制水平相关.
结论:
- 循环氧化酶-2 (COX-2) 抑制的程度在标准剂量内在纳普罗和塞莱科西布之间有显著的变化.
- 纳普罗的较大COX-2抑制与更明显的血压增加有关.
- 未来对NSAIDs的心血管风险评估应考虑药理学差异,包括COX抑制水平和患者特异性因素.
相关概念视频
Hypertension and Regulation of Blood Pressure
3.6K
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...
3.6K
Antihypertensive Drugs: Angiotensin II Receptor Blockers
2.4K
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...
2.4K
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
2.2K
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...
2.2K
Neural Regulation of Blood Pressure
6.7K
The neural regulation of blood pressure involves intricate interactions between the autonomic nervous system (ANS) and cardiovascular system, ensuring adequate perfusion of tissues. This regulation primarily occurs through baroreceptor and chemoreceptor reflexes, involving both short-term and long-term mechanisms.
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
6.7K
Hormonal Regulation of Blood Pressure
5.8K
Endocrinal or hormonal intervention in the cardiovascular system is predominantly exerted by the catecholamines - epinephrine and norepinephrine, as well as a slew of hormones that interact with renal function to modulate blood volume.
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
5.8K
Antihypertensive 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


