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Evaluation of the pathophysiological role of endothelial catecholamines

Grant number: 19/16805-4
Support Opportunities:Research Projects - Thematic Grants
Duration: October 01, 2021 - September 30, 2026
Field of knowledge:Biological Sciences - Pharmacology - Clinical Pharmacology
Principal Investigator:Gilberto de Nucci
Grantee:Gilberto de Nucci
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Pesquisadores principais:
Roberto Zatz ; Rodrigo Alvaro Brandão Lopes Martins
Associated researchers:André Almeida Schenka
Associated scholarship(s):23/03503-5 - Evaluation of the action of 6-nitrodopamine on the cardiovascular system in eNOS, nNOS and iNOS knockout mice, BP.IC
23/03460-4 - Effects of different antioxidant agents on 6-nitrodopamine production/release by human umbilical artery in vitro, BP.IC
21/14414-8 - Evaluation of the action of nitro-catecholamines in the cardiovascular system, BP.PD
+ associated scholarships 22/08232-7 - Pharmacological characterization of 6-Nitrodopamine in the systemic and renal hemodynamics of mammals and reptiles, BP.PD
22/07737-8 - Evaluation of the cardiovascular effect of 6-nitrodopamine in isolated atrium and perfused rat heart, BP.DD
22/08022-2 - Evaluation of chronic treatment of 6-nitronoradrenaline in rats, BP.DD
22/06644-6 - Evaluation of 6-nitronoradrenaline in rat vas deferens, BP.IC
21/13593-6 - Evaluation of chronic 6-nitrodopamine treatment in rats, BP.DD
21/13726-6 - Identification of molecules related to the synthesis of adrenaline, noradrenaline and dopamine in the endothelium of reptiles and mammals by immunohistochemistry and in situ hibridization, BP.PD
21/14120-4 - Evaluation of adrenergic beta antagonists in the vas deferens duct in rats, BP.IC - associated scholarships


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)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BRITTO-JUNIOR, JOSE; RIBEIRO, ANDRE; XIMENES, LUIZ; LIMA, ANTONIO TIAGO; JACINTHO, FELIPE FERNANDES; FREGONESI, ADRIANO; MONICA, FABIOLA Z.; ANTUNES, EDSON; DE NUCCI, GILBERTO. lpha1-adrenergic antagonists block 6-nitrodopamine contractions on the rat isolated epididymal vas deferen. European Journal of Pharmacology, v. 915, . (18/24971-9, 17/15175-1, 19/16805-4)
J. BRITTO-JÚNIOR; A.T. LIMA; J.S. SANTOS-XAVIER; P. GONZALEZ; F.Z. MÓNICA; R. CAMPOS; V.B. DE SOUZA; A.A. SCHENKA; E. ANTUNES; G. DE NUCCI. Relaxation of thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) by endothelium-derived 6-nitrodopamine. Brazilian Journal of Medical and Biological Research, v. 56, . (19/16805-4, 21/13593-6, 21/13726-6, 21/14414-8, 17/15175-1)
BRITTO-JUNIOR, JOSE; XIMENES, LUIZ; RIBEIRO, ANDRE; FREGONESI, ADRIANO; CAMPOS, RAFAEL; KIGUTI, LUIZ RICARDO DE ALMEIDA; MONICA, FABIOLA Z.; ANTUNES, EDSON; DE NUCCI, GILBERTO. 6-Nitrodopamine is an endogenous mediator of rat isolated epididymal vas deferens contractions induced by electric-field stimulation. European Journal of Pharmacology, v. 911, . (17/15175-1, 19/16805-4)

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