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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Bernak-Oliveira, Angelo [1] ; Guizoni, Daniele M. [2] ; Chiavegatto, Silvana [3, 4] ; Davel, Ana P. [2] ; V. Rossoni, Luciana [1]
Total Authors: 5
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: Life Sciences; v. 285, NOV 15 2021.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases
Grantee:Carlos Eduardo Negrão
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 11/16017-4 - Evaluation of the mechanisms involved on the endothelium-dependent vasodilation in aorta of isoproterenol-treated mice
Grantee:Angelo Bernak de Oliveira
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 17/06100-8 - Susceptibility and resilience to the effects of chronic psychosocial stress in adolescence: participation of the neuronal nitric oxide synthase (nNOS)
Grantee:Silvana Chiavegatto
Support Opportunities: Regular Research Grants