Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide

Autor(es)

Rodrigues, Serginara David ; da Silva, Maria Luiza Santos ; Martins, Laisla Zanetoni ; Gomes, Saskia Estela Biasotti ; Mariani, Noemia A. P. ; Silva, Erick J. R. ; Kushima, Helio ; Mattos, Bruna Rahal ; Rizzi, Elen ; Dias-Junior, Carlos Alan

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 331, p. 13-pg., 2023-10-15.

Resumo

Aims: Pregnancy hypertension-induced endothelial dysfunction associated with impairment of nitric oxide (NO) bioavailability and hemodynamic derangements is a challenging for urgent procedures requiring maternal anesthesia. The volatile anesthetic isoflurane has demonstrated NO-associated protective effects. However, this isoflurane-induced effect is still unclear in pregnancy hypertension. Therefore, the present study examined the potential protective effects of isoflurane anesthesia on endothelial dysfunction and hemodynamic changes induced by hypertensive pregnancy associated with fetal and placental growth restrictions. Materials and methods: Animals were distributed into four groups: normotensive pregnant rats (Preg), anesthetized pregnant rats (Preg+Iso), hypertensive pregnant rats (HTN-Preg), and anesthetized hypertensive pregnant rats (HTN-Preg+Iso). Systolic and diastolic pressures, mean arterial pressure (MAP), heart rate, fetal and placental weights, vascular contraction, endothelium-derived NO-dependent vasodilation, and NO levels were assessed. The vascular endothelial growth factor (VEGF) levels and endothelial NO synthase (eNOS) Serine (1177) phosphorylation (p-eNOS) expression were also examined. Key findings: Isoflurane produced more expressive hypotensive effects in the HTN-Preg+Iso versus Preg+Iso group, with respective reductions in MAP by 50 +/- 13 versus 25 +/- 4 mmHg (P < 0.05). Also, HTN-Preg+Iso compared to the HTN-Preg group showed (respectively) preventions against the weight loss of the fetuses (4.0 +/- 0.6 versus 2.8 +/- 0.6 g, P < 0.05) and placentas (0.37 +/- 0.06 versus 0.30 +/- 0.06 mg, P < 0.05), hyper-reactive vasocontraction response (1.8 +/- 0.4 versus 2.8 +/- 0.6 g, P < 0.05), impaired endothelium-derived NO-dependent vasodilation (84 +/- 8 versus 50 +/- 17 %, P < 0.05), reduced VEGF levels (147 +/- 46 versus 25 +/- 13 pg/mL, P < 0.05), and decreased p-eNOS expression (0.24 +/- 0.07 versus 0.09 +/- 0.05 arbitrary units, P < 0.05). Significance: Isoflurane anesthesia protects maternal endothelial function in pregnancy hypertension, and possibly endothelium-derived NO is involved. (AU)

• Processo FAPESP: 21/12010-7 - Disfunção endotelial em doenças hipertensivas da gestação
• Beneficiário: Valeria Cristina Sandrim
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/03135-8 - Impacto do esomeprazol na biodisponibilidade do oxido nítrico na Hipertensão Gestacional em ratas
• Beneficiário: Maria Luiza Santos da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 22/10773-6 - Avaliação dos efeitos do óxido nítrico derivado do nitrito de sódio sobre fatores angiogênicos e antiangiogênicos na hipertensão gestacional induzida por isquemia placentária em ratas
• Beneficiário: Sáskia Estela Biasotti Gomes
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 21/03792-1 - Avaliação dos efeitos do isoflurano na biodisponibilidade de óxido nítrico na hipertensão gestacional em ratas
• Beneficiário: Serginara David Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 21/08380-3 - Avaliação dos efeitos do inibidor da bomba de prótons na pressão arterial, função vascular e biodisponibilidade de óxido nítrico na hipertensão gestacional em ratas
• Beneficiário: Carlos Alan Candido Dias Junior
• Modalidade de apoio: Auxílio à Pesquisa - Regular