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

Author(s)

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

• Document type: Journal article
• Source: Life Sciences; v. 331, p. 13-pg., 2023-10-15.

Abstract

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)

• FAPESP's process: 21/12010-7 - Endothelial dysfunction in hypertensive disorders of pregnancy
• Grantee: Valeria Cristina Sandrim
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/03135-8 - Impact of esomeprazole on the nitric oxide bioavailability in Gestational Hypertension in rats
• Grantee: Maria Luiza Santos da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 22/10773-6 - Evaluation of the effects of nitric oxide derived from sodium nitrite on angiogenic and antiangiogenic factors in gestational hypertension induced by placental ischemia in rats
• Grantee: Sáskia Estela Biasotti Gomes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 21/03792-1 - Evaluation of isoflurane effects on nitric oxide bioavailability during the gestational hypertension in rats
• Grantee: Serginara David Rodrigues
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 21/08380-3 - Evaluation of the proton pump inhibitor effects on blood pressure, vascular function and nitric oxide bioavailability in gestational hypertension in rats
• Grantee: Carlos Alan Candido Dias Junior
• Support Opportunities: Regular Research Grants