Avaliação dos efeitos do isoflurano na biodisponibilidade de óxido nítrico na hipertensão gestacional em ratas
Data
2023-07-31
Autores
Rodrigues, Serginara David
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A disfunção endotelial induzida por hipertensão na gravidez associada a distúrbios hemodinâmicos é um desafio para procedimentos urgentes que requerem anestesia materna. O anestésico volátil isoflurano demonstrou efeitos protetores associados ao óxido nítrico (NO). O comprometimento da biodisponibilidade do NO também tem sido relacionado a distúrbios hipertensivos da gravidez. No entanto, esse efeito induzido pelo isoflurano ainda não está claro na hipertensão na gravidez. Portanto, o presente estudo examinou os potenciais efeitos protetores da anestesia com isoflurano na disfunção endotelial e nas alterações hemodinâmicas induzidas pela gravidez hipertensiva associada à restrição do crescimento fetal e placentário. Os animais foram distribuídos em quatro grupos: ratas grávidas normotensas (Preg), ratas grávidas anestesiadas (Preg+Iso), ratas grávidas hipertensas (HTN-Preg) e ratas grávidas hipertensas anestesiadas (HTN-Preg+Iso). Pressões arteriais sistólica, diastólica e média, frequência cardíaca, peso fetal e placentário, contração vascular, vasodilatação dependente de NO derivado do endotélio e níveis de NO foram avaliados. Os níveis do fator de crescimento endotelial vascular (VEGF) e a expressão da fosforilação da NO sintase (eNOS) Serina (1177) (p-eNOS) também foram examinados. Nossos resultados demonstram que a anestesia com isoflurano produziu efeitos hipotensores mais expressivos, efeitos relacionados à prevenção contra perdas de peso fetal e placentário, resposta vasocontrátil hiper-reativa, vasodilatação dependente de NO derivado do endotélio prejudicada, níveis reduzidos de VEGF e expressão diminuída de p-eNOS nas ratas HTN-Preg+Iso comparadas ao grupo HTN-Preg. Em conclusão, a anestesia com isoflurano protege a função endotelial materna na hipertensão da gravidez e, possivelmente, o NO derivado do endotélio está envolvido.
Pregnancy hypertension-induced endothelial dysfunction associated with hemodynamic derangements is a challenge for urgent procedures that require maternal anesthesia. The volatile anesthetic isoflurane has demonstrated nitric oxide (NO)-associated protective effects. Impairment of NO bioavailability has also been related to hypertensive disorders of pregnancy. 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 restriction. 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, diastolic and mean arterial pressures, 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. Our results demonstrate that isoflurane anesthesia produced more expressive hypotensive effects, which were related to the preventions against fetal and placental weight losses, hyper-reactive vasocontraction response, impaired endothelium-derived NO-dependent vasodilation, reduced VEGF levels, and decreased p-eNOS expression in the HTN-Preg+Iso rats compared to HTNPreg group. In conclusion, isoflurane anesthesia protects maternal endothelial function in pregnancy hypertension, and possibly endothelium-derived NO is involved.
Pregnancy hypertension-induced endothelial dysfunction associated with hemodynamic derangements is a challenge for urgent procedures that require maternal anesthesia. The volatile anesthetic isoflurane has demonstrated nitric oxide (NO)-associated protective effects. Impairment of NO bioavailability has also been related to hypertensive disorders of pregnancy. 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 restriction. 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, diastolic and mean arterial pressures, 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. Our results demonstrate that isoflurane anesthesia produced more expressive hypotensive effects, which were related to the preventions against fetal and placental weight losses, hyper-reactive vasocontraction response, impaired endothelium-derived NO-dependent vasodilation, reduced VEGF levels, and decreased p-eNOS expression in the HTN-Preg+Iso rats compared to HTNPreg group. In conclusion, isoflurane anesthesia protects maternal endothelial function in pregnancy hypertension, and possibly endothelium-derived NO is involved.
Descrição
Palavras-chave
Disfunção endotelial, Hipertensão gestacional, Isoflurano, Óxido nítrico, Distúrbios hemodinâmicos, Anestesia, Endothelial dysfunction, Gestational hypertension, Isoflurane, Nitric oxide, Hemodynamic derangements, Anesthesia