Effects Of The Kynurenine Pathway On The Vascular Function Of Late Pregnant Mice

Effects Of The Kynurenine Pathway On The Vascular Function Of Late Pregnant Mice

• Autor
• Nayana Yared Batista
• Co-autores
• Everton de Oliveira Pinto , Alecsander Fabricio M. Bressan , Rita de Cássia Aleixo Tostes Passaglia , José Wilson do Nascimento Corrêa
• Resumo

• Pregnancy imposes important and transient cardiocirculatory changes on the body. There is high demand for tryptophan, a precursor to the Kynurenine (KYN) pathway via an increased activity of indoleamine 2,3-dioxigenase (IDO) enzyme in the placenta. IDO is also expressed in the perivascular adipose tissue, vascular endothelium and in immune cells. Objective: To evaluate the involvement of KYN in the vascular changes observed in late pregnancy. Methods: Female (n=6/group) and male (n=3/group) C57/BL-06 mice, 30-35g (CEUA 167/2019 FMRP-USP) were used for mating. On the 20th day of pregnancy, vascular reactivity tests against phenylephrine and acetylcholine (10-11 to 10-4M) were performed on aortic rings pre-incubated with 10-3M inhibitors (1-MT and IKMO) or 10-4 M metabolites (L-Kynurenine, Kynurenic Acid and 3-hydroxyquinurenine) of the KYN pathway. Results: 1-MT (IDO inhibitor) and I-KMO (Kynurenine-3-monooxygenase inhibitor) increased the maximum effect (Emáx) for phenylephrine, without changing its potency (pD2). Quinurenic acid and 3-HKYN reduced vasoconstriction, while L-KYN did not modify the vasoconstrictor effect. The metabolites potentiated the vasoconstrictor response, being the response to L-KYN more effective. For vasodilation, both inhibitors and all metabolites decreased the Emáx for acetylcholine, except for quinurenic acid. There was a significant reduction in the vasodilator potency of acetylcholine in the presence of metabolites and inhibitors (Table 1). Conclusion: Our results suggest that the Kynurenine pathway modulates the vascular response in late pregnancy and contributes to mechanisms to decrease vasoconstriction.

    

  Table 1 - Effects of KYN pathway inhibitors and metabolites

   

  Table 1 - Effects of KYN pathway inhibitors and metabolites

   Vasoconstriction

   Vehicle

  1-MT

  I-KMO

  Vehicle

  L-KYN

  KYN Ac.

  3-HKYN

  Emax

  93.36±2.02

  148.2±3.79*

  127.8±3.93*#

  108.7±1.75

  105.6±2.1

  92.21±3.21*

  97.93±2.87*

  pD2

  7.15±0.06

  6.97±0.05

  7.35±0.053# 

   7.41±0.05               

  10.66±0.16* 

   7.97±0.16*

  8.85±0.16*

   

  Vasodilation

   

   

   

   

   

   

   

   

   

   

   

   

  Emáx

  101.9±0.98

  90.53±1.2*

  96.45±1.5*#  

  92.87±0.98

  71.61±2.01* 

  89.27±1.52

  64.26±1.1*

  pD2

  7.34±0.02

  6.8±0.03* 

   6.96±0.03*#

  7.2±0.02

  6.5±0.06*

  6.67±0.03*

  6.62±0.04*

   

  *P<0.05 vs. vehicle. #P<0.05 vs. 1-MT

   

• Palavras-chave
• Vascular reactivity, Pregnancy, Tryptophan, IDO, Kynurenine
• Modalidade
• Pôster
• Área Temática
• Disfunção endotelial