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.