Evaluation of the pathophysiological role of endothelial catecholamines

Abstract

The endothelium is an organ capable of regulating vascular tone through the release of endothelium-derived relaxing factors such as nitric oxide, prostacyclin, etc., or endothelium-derived contracting factors as endothelins, prostanoid. In addition, the current physiological concept poses that such regulation can also occur through the release of exclusively neural-derived catecholamines. Our group has demonstrated in tissues isolated from reptiles that the endothelium is also a source of catecholamines, since the contraction of the snake aorta induced by electrical field stimulation (EFS) is abolished by adrenergic antagonists and by removing the endothelium. As described in this project, the pathophysiology role of endothelial catecholamines in humans will be evaluated by in vitro pharmacological tests, using human arteries, veins and cardiac tissue, and a through pharmacological clinical trials. The observation that the endothelium could be a source of catecholamines was supported by the identification of the enzyme tyrosine hydroxylase in the snake endothelium by immunohistochemistry. Accidentally, this observation was also extended for human endothelial cells. As described in the project, the physiological and pathophysiological role of endothelial catecholamines in humans is being evaluated through in vitro pharmacological approaches using human arteries and veins, and an in vivo pharmacological approach through clinical trials. It also aims to support the observations obtained in pharmacological tests in vitro and in vivo with a morphological substrate through the identification and possible quantification of the metabolic pathway of catecholamines by immunohistochemistry, fluorescence in situ hybridization (FISH) and by RNA in situ hybridization assay (RNA-ISH) with RNA Scope® technology. It is expected that the information collected will demonstrate the physiological and pathophysiological relevance of endothelial catecholamines in humans and will determine its importance in relation to neural adrenergic control. It will also be investigated whether the endothelium has the ability to synthesize and release other vasoactive amines, such as serotonin and histamine. (AU)