Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy

Biosci Rep. 2024 Jun 26;44(6):BSR20240192. doi: 10.1042/BSR20240192.

Abstract

Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n=28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) versus 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.

Keywords: isoflurane; metalloproteinase; nitric oxide; non-pregnant rats; pregnancy.

MeSH terms

  • Anesthetics, Inhalation / pharmacology
  • Animals
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Female
  • Hemodynamics / drug effects
  • Isoflurane* / pharmacology
  • Matrix Metalloproteinase 2* / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Nitric Oxide* / metabolism
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilation* / drug effects

Substances

  • Isoflurane
  • Nitric Oxide
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Anesthetics, Inhalation
  • Mmp2 protein, rat
  • Mmp9 protein, rat