Endothelial modulation of a nitric oxide donor complex-induced relaxation in normotensive and spontaneously hypertensive rats
Autor: | Simone R. Potje, Marcella D. Grando, Jéssica A. Troiano, Lusiane Maria Bendhack, Cristina Antoniali, Roberto Santana da Silva, Murilo E. Graton |
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Přispěvatelé: | Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP) |
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Muscle Relaxation VASODILATAÇÃO Vasodilation 030204 cardiovascular system & hematology TERPY SHR chemistry.chemical_compound 0302 clinical medicine Coordination Complexes Enos Rats Inbred SHR General Pharmacology Toxicology and Pharmaceutics Mesenteric arteries Oxadiazoles biology Chemistry Mesenteric artery General Medicine Potassium channel Mesenteric Arteries NG-Nitroarginine Methyl Ester medicine.anatomical_structure eNOS cardiovascular system Nitric oxide donor medicine.medical_specialty Nitric Oxide Synthase Type III Endothelium Ruthenium General Biochemistry Genetics and Molecular Biology Nitric oxide 03 medical and health sciences Quinoxalines Internal medicine Potassium Channel Blockers medicine Animals Nitric Oxide Donors Tetraethylammonium Dose-Response Relationship Drug biology.organism_classification Rats 030104 developmental biology Endocrinology Guanylate Cyclase Vascular Resistance Endothelium Vascular Soluble guanylyl cyclase |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
ISSN: | 0024-3205 |
DOI: | 10.1016/j.lfs.2018.03.055 |
Popis: | Made available in DSpace on 2018-12-11T17:24:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-05-15 We hypothesized that endothelium modulates relaxation induced by a nitric oxide (NO) donor ruthenium complex (TERPY, [Ru(terpy)(bdq)NO]3+) in mesenteric arteries of normotensive and spontaneously hypertensive (SHR) rats in different ways. We analyzed the mechanism involved in TERPY-induced relaxation in the second and third branches of mesenteric arteries and investigated how endothelium contributes to the TERPY vasodilator effect on SHR blood vessels. TERPY induced concentration-dependent relaxation in endothelium-denuded (E-) and endothelium-intact (E+) mesenteric arteries of normotensive rats and SHR. Pretreatment with ODQ (which inhibits soluble guanylyl cyclase) or TEA (tetraethylammonium, which blocks potassium channels) significantly reduced the TERPY vasodilator effect on E- mesenteric arteries of normotensive rats and SHR. The presence of endothelium shifted the concentration-effect curves for TERPY in E+ mesenteric arteries of normotensive rats to the right. Conversely, the presence of endothelium shifted the concentration-effect curves for TERPY in the case of SHR E+ mesenteric arteries to the left, which suggested increased potency. L-NNA, a more selective endothelial NO synthase (eNOS) inhibitor, reduced TERPY potency in SHR. The presence of endothelium and notably of NOS contributed to the TERPY vasodilator action in SHR: TERPY promoted eNOS Ser1177 phosphorylation with consequent NO production and increased soluble guanylyl cyclase activity, which may have directly activated potassium channels. Programa Multicêntrico de Pós-graduação em Ciências Fisiológicas - SBFis, São Paulo State University (UNESP), School of Dentistry, Araçatuba, Department of Basic Sciences, Brazil University of São Paulo (USP), Faculty of Pharmaceutical Sciences of Ribeirão Preto, Department of Physics and Chemistry, Brazil Programa Multicêntrico de Pós-graduação em Ciências Fisiológicas - SBFis, São Paulo State University (UNESP), School of Dentistry, Araçatuba, Department of Basic Sciences, Brazil. Electronic address: crisant@foa.unesp.br |
Databáze: | OpenAIRE |
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