Evaluation of isoflurane effects on nitric oxide bioavailability during the gestational hypertension in rats

• Grant number: 21/03792-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2022
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Serginara David Rodrigues
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Although there were great advances in the diagnosis and treatment of hypertension during pregnancy, such conditions are still among the highest causes of maternal and perinatal morbidity and mortality worldwide. Nitric oxide (NO) derived from the endothelial nitric oxide synthase (eNOS) enzyme and matrix metalloproteinases (MMP-2 and MMP-9), play important roles in the vascular endothelium, and any change in these factors may be involved in the pathophysiology of gestational hypertension. Inhalation anesthesia with isoflurane may influence the NO bioavailability, and consequently, mediate cardiac preconditioning during pregnancy. Studies that evaluate the changes in hemodynamics and blood gases during hypertensive pregnancy in view of exposure to inhaled anesthetic are scarce. Furthermore, assuming that isoflurane induces the recruitment of eNOS, increasing the bioavailability of NO, and consequently reducing the levels of MMPs, the objective of this study is to assess the expression of eNOS, the NO bioavailability, and examining the activity of MMP-2 and MMP-9 in pregnant hypertensive rats under anesthesia with isoflurane. Thirty-two female Wister rats will be randomly divided in four groups (8 animals per group): normotensive pregnant rats (G1), hypertensive pregnant rats (G2), normotensive pregnant rats under isoflurane anesthesia (G3), hypertensive pregnant rats under isoflurane anesthesia (G4). The DOCA-salt hypertensive model will be used to induce gestational hypertension in the experimental rats. On the 20th gestational day, the rats from G3 and G4 will be anesthetized with isoflurane, and all rats will be killed by exsanguination. After euthanasia, the pregnant uterus will be excised and opened, and placental weight, the number of fetuses and their total weight will be recorded. Finally, some variables will be examined: vascular reactivity; expression of the eNOS by Western Blot analysis; estimation of lipid peroxidation; measurement of MMPs by zymography; estimation of the NO concentration using the Griess and Sievers methods. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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. Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide. Life Sciences, v. 331, p. 13-pg., 2023-10-15. (21/12010-7, 20/03135-8, 22/10773-6, 21/03792-1, 21/08380-3)

MARTINS, LAISLA ZANETONI; DA SILVA, MARIA LUIZA SANTOS; RODRIGUES, SERGINARA DAVID; GOMES, SASKIA ESTELA BIASOTTI; MOLEZINI, LAURA; RIZZI, ELEN; MONTENEGRO, MARCELO FREITAS; DIAS-JUNIOR, CARLOS ALAN. Sodium Nitrite Attenuates Reduced Activity of Vascular Matrix Metalloproteinase-2 and Vascular Hyper-Reactivity and Increased Systolic Blood Pressure Induced by the Placental Ischemia Model of Preeclampsia in Anesthetized Rats. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 16, p. 16-pg., 2023-08-01. (21/12010-7, 20/03135-8, 22/10773-6, 21/03792-1, 21/08380-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RODRIGUES, Serginara David. Evaluation of the effects of isoflurane on the bioavailability of nitric oxide in gestational hypertension in rats. 2023. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.