Evaluation of vascular reactivity and gelatinolytic activity of metalloproteinases 2 and 9 following isoflurane anesthesia in pregnant rats

• Grant number: 19/06072-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2019
• End date: May 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Carolina Rosa Rodrigues de Souza
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The use of inhalational anesthetics has been increasingly studied in non-elective surgeries in pregnant women, since this approach is necessary in emergency procedures. Thus, examining the vascular repercussions of anesthesia at the gestation may provide support for assessing the cardiovascular effects on the mother, minimizing the risk of fetal impairment, and preventing preterm labor. Isoflurane is one of the most used volatile anesthetics for general anesthesia, however, although it presents low blood-gas partition coefficient, its security in pregnancy has not yet been stablished. It is already known that isoflurane may influence the vasomotor response, compromising endothelium-dependent vasodilatation caused by the release of nitric oxide (NO). In addition, reduction in NO bioavailability has been associated with increased activity of metalloproteinases (MMPs), particularly MMP-2 and MMP-9. However, no previous study has evaluated vascular repercussions and gelatinolytic activity of MMPs after isoflurane anesthesia in pregnant rats. Therefore, our hypothesis is that after isoflurane anesthesia, there is an impairment of endothelium-dependent vasodilation and this effect is related to increases in activity of MMP-2 and MMP-9 in the vessel. Therefore, the study aims to determine the effects on vascular reactivity of pregnant rats anesthetized with isoflurane, as well as its influence on the gelatinolytic activity of MMP-2 and -9. To this end, Wistar rats will be randomly divided into groups, pregnant and virgin under anesthetic agents (or not) and will be used for posterior analysis of vascular responsiveness to constrictors and dilators in aorta rings with endothelium (E+) or without (E-). Also, biochemical assays will be done in aorta, as following: zymography to gelatinolytic activity of MMPs and Griess to NO concentrations.