Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats.
Diabetes mellitus is associated with reactive oxygen and nitrogen species accumulation. Behavioral stress increases nitric oxide production, which may trigger a massive impact on vascular cells and accelerate cardiovascular complications under oxidative stress conditions such as Diabetes. For this study, type-1 Diabetes mellitus was induced in Wistar rats by intraperitoneal injection of streptozotocin. After 28 days, cumulative concentration-response curves for angiotensin II were obtained in endothelium-intact carotid rings from diabetic rats that underwent to acute restraint stress for 3h. The contractile response evoked by angiotensin II was increased in carotid arteries from diabetic rats. Acute restraint stress did not alter angiotensin II-induced contraction in carotid arteries from normoglycaemic rats. However acute stress combined with Diabetes increased angiotensin II-induced contraction in carotid rings. Western blot experiments and the inhibition of nitric oxide synthases in functional assays showed that neuronal, endothelial and inducible nitric oxide synthase isoforms contribute to the increased formation of peroxynitrite and contractile hyperreactivity to angiotensin II in carotid rings from stressed diabetic rats. In summary, these findings suggest that the increased superoxide anion generation in carotid arteries from diabetic rats associated to the increased local nitric oxide synthases expression and activity induced by acute restrain stress were responsible for exacerbating the local formation of peroxynitrite and the contraction induced by angiotensin II.
Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University from Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: josimardornelas@hotmail.com.br.
Josimar D
JD
Moreira
Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences from Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Larissa
L
Pernomian
Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences from Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Mayara S
MS
Gomes
Department of Internalization - Binational Campus, Federal University from Amapá, Oiapoque, AP, Brazil.
Rafael P
RP
Moreira
Institutional Capacity Building Program, Coordination of Earth Science and Ecology, Museum Paraense Emílio Goeldi (MPEG), Belém, PA, Brazil.
Alejandro F
AF
do Prado
Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences from Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Carlos H T P
CH
da Silva
Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences from Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Ana M
AM
de Oliveira
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000737:chemistry / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000096:biosynthesis*; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
D000804:Angiotensin II; D030421:Peroxynitrous Acid; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
Acute restraint stress; Nitric oxide synthases; Reactive nitrogen species; Reactive oxygen species; Renin-angiotensin-system; Type-1 Diabetes