Endothelin Has Biological Actions at Pathophysiological Concentrations
Endothelin Has Biological Actions at Pathophysiological Concentrations
复制标题
DOI：
10.1161/01.cir.83.5.1808
复制
发表时间：
1991-05
期刊：
影响因子：
37.8
通讯作者：
A. Lerman;F. Hildebrand;L. Aarhus;J. Burnett
中科院分区：
文献类型：
--
作者：
A. Lerman;F. Hildebrand;L. Aarhus;J. Burnett
背景内皮素是一种内皮源性肽，在体外能引起动脉和静脉平滑肌的持续收缩。一些研究已经确定内皮素在药理学浓度下是体内全身、肾脏和冠状动脉血管收缩剂。这种浓度的内皮素是与激活的肾素-血管紧张素-醛固酮系统相关的抗心房利尿剂。最近的研究表明，内皮素存在于血浆中，并且其血浆浓度在与全身和肾血管收缩相关的各种病理状态中增加。迄今为止，仍不清楚循环内皮素的这种增加是否与生物活性相关。因此，本研究的目的是通过给予外源性内皮素来确定内皮素对心肾和内分泌功能的生物学作用，该外源性内皮素达到了在各种病理生理条件下已报告的血浆浓度。方法和结果实验在两组麻醉犬中进行。在第1组中，以2.5 ng/kg/ml（n =6）静脉输注内皮素-1，使循环浓度加倍。第2组（n =8）接受生理盐水溶媒作为时间对照。目前的研究表明，血浆内皮素浓度的两倍增加并不影响平均血压或冠状动脉血流量。心率和心输出量下降与肾和全身血管阻力增加和抗利尿有关。结论外源性内皮素产生的病理生理血浆浓度的内皮素具有生物学作用。这些研究支持内源性内皮素作为一种潜在的病理生理性血管收缩肽激素在心血管、肾脏和内分泌功能调节中的功能作用。
BackgroundEndothelin is an endothelium-derived peptide that produces sustained contraction of arterial and venous smooth muscle in vitro. Several studies have established endothelin as a systemic, renal, and coronary vasoconstrictor in vivo at pharmacological concentrations. Such concentrations of endothelin were antinatriuretic in association with activation of the renin-angiotensin-aldosterone system. Recent studies have demonstrated that endothelin is present in the plasma and that its plasma concentrations are increased in various pathological states associated with systemic and renal vasoconstriction. To date, it remains unclear if such increases in circulating endothelin are associated with biological activity. Thus, the objective of this study was to determine the biological action of endothelin on cardiorenal and endocrine function through administration of exogenous endothelin, which achieves plasma concentrations that have been reported in various pathophysiological conditions. Methods and ResultsExperiments were conducted in two groups of anesthetized dogs. In group 1, endothelin-1 was infused intravenously at 2.5 ng/kg/ml (n =6), which produced a doubling of circulating concentrations. Group 2 (n =8) received saline vehicle to serve as a time control. The current studies demonstrate that a twofold increase in plasma endothelin concentrations did not affect mean blood pressure or coronary blood flow. Heart rate and cardiac output decreased in association with increased renal and systemic vascular resistances and antinatriuresis. ConclusionsThe present studies demonstrate that endothelin at pathophysiological plasma concentrations produced by exogenous endothelin has biological action. These studies support a functional role for endogenous endothelin as a potentially pathophysiological vasoconstrictor peptide hormone in the regulation of cardiovascular, renal, and endocrine function.