The protective role of neuronal nitric oxide synthase in endothelial vasodilation in chronic beta-adrenoceptor overstimulation

Autor(es)

Bernak-Oliveira, Angelo ^[1] ; Guizoni, Daniele M. ^[2] ; Chiavegatto, Silvana ^{[3, 4]} ; Davel, Ana P. ^[2] ; V. Rossoni, Luciana ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Prof Lineu Prestes Av 1524, Rm 225, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Monteiro Lobato St 255, BR-13083862 Campinas, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci ICB, Dept Pharmacol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo Med Sch FMUSP, Inst Psychiat IPq, Dept Psychiat, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 285, NOV 15 2021.
• Citações Web of Science: 0

Resumo

Aims: Nitric oxide synthases (NOSs) are key enzymes regulating vascular function. Previously, we reported that beta-adrenergic (beta-AR) overstimulation, a common feature of cardiovascular diseases, did not impair endotheliumdependent vasodilation, although it resulted in endothelial NOS (eNOS) uncoupling and reduced NO bioavailability. In addition to NO, neuronal NOS (nNOS) produces H2O2, which contributes to vasodilation. However, there is limited information regarding vascular beta-AR signaling and nNOS. In the present study, we assessed the possible role of nNOS-derived H2O2 and caveolins on endothelial vasodilation function following beta-AR overstimulation. Main methods: Male C57BL/6 wild-type and nNOS knockout mice (nNOS /) were treated with the eta-AR agonist isoproterenol (ISO, 15 mg.kg (-1).day (-1), s.c.) or vehicle (VHE) for seven days. Relaxation responses of aortic rings were evaluated using wire myograph and H2O2 by Amplex Red. Key findings: Acetylcholine- or calcium ionophore A23187-induced endothelium-dependent relaxation was similar in aortic rings from VHE and ISO. However, this relaxation was significantly reduced in aortas from ISO compared to VHE when (1) caveolae were disrupted, (2) nNOS was pharmacologically inhibited or genetically suppressed and (3) H2O2 was scavenged. NOS-derived H2O2 production was higher in the aortas of ISO mice than in those of VHE mice. Aortas from ISO-treated mice showed increased expression of caveolin-1, nNOS and catalase, while caveolin-3 expression did not change. Significance: The results suggest a role of caveolin-1 and the nNOS/H2O2 vasodilatory pathway in endotheliumdependent relaxation following beta-AR overstimulation and reinforce the protective role of nNOS in cardiovascular diseases associated with high adrenergic tone. (AU)

• Processo FAPESP: 07/58853-8 - Papel dos receptores beta1-, beta2- e beta3-adrenergicos nas alterações de função vascular e síntese de citocinas pró-inflamatórias induzidas pelo tratamento com isoproterenol em camundongos
• Beneficiário: Luciana Venturini Rossoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/50048-1 - Bases celulares e funcionais do exercício físico na doença cardiovascular
• Beneficiário: Carlos Eduardo Negrão
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/16017-4 - Avaliação dos mecanismos envolvidos na vasodilatação dependente do endotélio em aorta de camundongos tratados com isoproterenol
• Beneficiário: Angelo Bernak de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/06100-8 - Suscetibilidade e resiliência aos efeitos do estresse psicossocial crônico na adolescência: estudo da participação da enzima neuronal de síntese do óxido nítrico (nNOS)
• Beneficiário: Silvana Chiavegatto
• Modalidade de apoio: Auxílio à Pesquisa - Regular