Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats

Endothelium-derived nitric oxide (NO)-induced vasodilation is impaired in pregnancy hypertension. However, the role of perivascular adipose tissue (PVAT)-derived hydrogen sulfide (H<sub>2</sub>S), as an alternative for counteracting vascular dysfunction, is incompletely clear in hyperten...

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Main Authors: Priscilla Bianca de Oliveira, Gabriela Palma Zochio, Edileia Souza Paula Caetano, Maria Luiza Santos da Silva, Carlos Alan Dias-Junior
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/12/11/1919
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author Priscilla Bianca de Oliveira
Gabriela Palma Zochio
Edileia Souza Paula Caetano
Maria Luiza Santos da Silva
Carlos Alan Dias-Junior
author_facet Priscilla Bianca de Oliveira
Gabriela Palma Zochio
Edileia Souza Paula Caetano
Maria Luiza Santos da Silva
Carlos Alan Dias-Junior
author_sort Priscilla Bianca de Oliveira
collection DOAJ
description Endothelium-derived nitric oxide (NO)-induced vasodilation is impaired in pregnancy hypertension. However, the role of perivascular adipose tissue (PVAT)-derived hydrogen sulfide (H<sub>2</sub>S), as an alternative for counteracting vascular dysfunction, is incompletely clear in hypertensive disorders of pregnancy. Therefore, PVAT-derived H<sub>2</sub>S-induced vasodilation was investigated in pregnancy hypertension-induced endothelial dysfunction. Non-pregnant (Non-Preg) and pregnant (Preg) rats were submitted (or not) to the deoxycorticosterone (DOCA)-salt protocol and assigned as follows (<i>n</i> = 10/group): Non-Preg, Non-Preg+DOCA, Preg, and Preg+DOCA groups. Systolic blood pressure (SBP), angiogenesis-related factors, determinant levels of H<sub>2</sub>S (PbS), NO (NOx), and oxidative stress (MDA) were assessed. Vascular changes were recorded in thoracic aortas with PVAT and endothelium (intact and removed layers). Vasorelaxation responses to the substrate (L-cysteine) for the H<sub>2</sub>S-producing enzyme cystathionine-γ-lyase (CSE) were examined in the absence and presence of CSE-inhibitor DL-propargylglycine (PAG) in thoracic aorta rings pre-incubated with cofactor for CSE (pyridoxal-5 phosphate: PLP) and pre-contracted with phenylephrine. Hypertension was only found in the Preg+DOCA group. Preg+DOCA rats showed angiogenic imbalances and increased levels of MDA. PbS, but not NOx, showed increased levels in the Preg+DOCA group. Pre-incubation with PLP and L-cysteine elevated determinants of H<sub>2</sub>S in PVAT and placentas of Preg-DOCA rats, whereas no changes were found in the aortas without PVAT. Aortas of Preg-DOCA rats showed that PVAT-derived H<sub>2</sub>S-dependent vasodilation was greater compared to endothelium-derived H<sub>2</sub>S, whereas PAG blocked these responses. PVAT-derived H<sub>2</sub>S endogenously stimulated with the amino acid L-cysteine may be an alternative to induce vasorelaxation in endothelial dysfunction related to pregnancy hypertension.
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spelling doaj.art-0e140f6f426e42ea87b05461fbc5a4502023-11-24T14:25:36ZengMDPI AGAntioxidants2076-39212023-10-011211191910.3390/antiox12111919Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in RatsPriscilla Bianca de Oliveira0Gabriela Palma Zochio1Edileia Souza Paula Caetano2Maria Luiza Santos da Silva3Carlos Alan Dias-Junior4Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, SP, BrazilDepartment of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, SP, BrazilDepartment of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, SP, BrazilDepartment of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, SP, BrazilDepartment of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, SP, BrazilEndothelium-derived nitric oxide (NO)-induced vasodilation is impaired in pregnancy hypertension. However, the role of perivascular adipose tissue (PVAT)-derived hydrogen sulfide (H<sub>2</sub>S), as an alternative for counteracting vascular dysfunction, is incompletely clear in hypertensive disorders of pregnancy. Therefore, PVAT-derived H<sub>2</sub>S-induced vasodilation was investigated in pregnancy hypertension-induced endothelial dysfunction. Non-pregnant (Non-Preg) and pregnant (Preg) rats were submitted (or not) to the deoxycorticosterone (DOCA)-salt protocol and assigned as follows (<i>n</i> = 10/group): Non-Preg, Non-Preg+DOCA, Preg, and Preg+DOCA groups. Systolic blood pressure (SBP), angiogenesis-related factors, determinant levels of H<sub>2</sub>S (PbS), NO (NOx), and oxidative stress (MDA) were assessed. Vascular changes were recorded in thoracic aortas with PVAT and endothelium (intact and removed layers). Vasorelaxation responses to the substrate (L-cysteine) for the H<sub>2</sub>S-producing enzyme cystathionine-γ-lyase (CSE) were examined in the absence and presence of CSE-inhibitor DL-propargylglycine (PAG) in thoracic aorta rings pre-incubated with cofactor for CSE (pyridoxal-5 phosphate: PLP) and pre-contracted with phenylephrine. Hypertension was only found in the Preg+DOCA group. Preg+DOCA rats showed angiogenic imbalances and increased levels of MDA. PbS, but not NOx, showed increased levels in the Preg+DOCA group. Pre-incubation with PLP and L-cysteine elevated determinants of H<sub>2</sub>S in PVAT and placentas of Preg-DOCA rats, whereas no changes were found in the aortas without PVAT. Aortas of Preg-DOCA rats showed that PVAT-derived H<sub>2</sub>S-dependent vasodilation was greater compared to endothelium-derived H<sub>2</sub>S, whereas PAG blocked these responses. PVAT-derived H<sub>2</sub>S endogenously stimulated with the amino acid L-cysteine may be an alternative to induce vasorelaxation in endothelial dysfunction related to pregnancy hypertension.https://www.mdpi.com/2076-3921/12/11/1919hydrogen sulfideperivascular adipose tissueendothelial dysfunctionpregnancy hypertension
spellingShingle Priscilla Bianca de Oliveira
Gabriela Palma Zochio
Edileia Souza Paula Caetano
Maria Luiza Santos da Silva
Carlos Alan Dias-Junior
Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats
Antioxidants
hydrogen sulfide
perivascular adipose tissue
endothelial dysfunction
pregnancy hypertension
title Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats
title_full Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats
title_fullStr Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats
title_full_unstemmed Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats
title_short Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats
title_sort vasodilator responses of perivascular adipose tissue derived hydrogen sulfide stimulated with l cysteine in pregnancy hypertension induced endothelial dysfunction in rats
topic hydrogen sulfide
perivascular adipose tissue
endothelial dysfunction
pregnancy hypertension
url https://www.mdpi.com/2076-3921/12/11/1919
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