VEGFR 2 in vascular smooth muscle cells mediates H 2 S-induced dilation of the rat cerebral basilar artery

Microvasc Res. 2022 May;141:104309. doi: 10.1016/j.mvr.2021.104309. Epub 2022 Jan 4.

Abstract

Introduction: The aim of present study was to study whether the vascular endothelial growth factor receptor 2 (VEGFR2) mediates hydrogen sulfide (H2S)-induced relaxation of the rat cerebral vasculature.

Methods: Relaxation of cerebral basilar artery (CBA) and vascular smooth muscle cells (VSMCs) was measured by using a pressure myograph system and image analysis system, respectively. The intracellular calcium concentration ([Ca2+]i) in VSMCs was detected using fluorescence imaging analysis.

Results: We found that H2S donor NaHS induced significant relaxation of VSMCs from the CBA of wild type rat, but in VEGFR2 knockdown VSMCs, NaHS-induced relaxation reduced markedly. In addition, NaHS-induced vasodilation of rat CBA also attenuated obviously when the expression of VEGFR2 was knocked down in vivo. In addition, pretreatment with the VEGFR2 blocker SU5416 likewise lowered the NaHS-induced relaxation of rat CBA. Nevertheless, the VEGFR2 agonist, vascular endothelial growth factor 164 (VEGF164), induced a concentration-dependent relaxation of CBA, which is similar to the effect of NaHS. Furthermore, we found that both NaHS and VEGF164 significantly inhibited the U46619-induced increase of [Ca2+]i fluorescence intensity in the VSMCs. However, the inhibitory effect of NaHS on the [Ca2+]i fluorescence intensity in VSMCs was markedly inhibited by pretreatment with SU5416 or VEGFR2 knockdown.

Conclusion: These findings indicated that H2S-induced CBA dilation and reduction of [Ca2+]i in VSMCs occur by acting on VEGFR2.

Keywords: Cerebral basilar artery; Dilation; Hydrogen sulfide; Intracellular calcium concentrations; VEGFR(2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basilar Artery / metabolism
  • Dilatation
  • Hydrogen Sulfide* / metabolism
  • Hydrogen Sulfide* / pharmacology
  • Muscle, Smooth, Vascular*
  • Rats
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2
  • Hydrogen Sulfide