VEGFR₂ in vascular smooth muscle cells mediates H₂S-induced dilation of the rat cerebral basilar artery

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.