Evidence in Favor of Calcium-Sensing Receptor in L-Cysteine-Mediated Vasorelaxation of Mouse Thoracic Aorta.

INTRODUCTION

In our study, the possible role of the calcium-sensing receptor (CaSR) pathway in L-cysteine-/hydrogen sulfide (H2S)-induced vasorelaxations was investigated in isolated mouse thoracic aorta tissue.

METHODS

For this purpose, vasorelaxations to L-cysteine (H2S substrate; 1 µ<sc>m</sc>-10 m<sc>m</sc>) and calindol (CaSR agonist; 0.3-10 μ<sc>m</sc>) were measured in endothelial-intact and -denuded thoracic aorta segments contracted with phenylephrine (5 μ<sc>m</sc>). Also, the effects of propargylglycine (PAG) and Calhex-231, cystathionine-gamma-lyase (CSE) and CaSR inhibitor, respectively, on L-cysteine- and calindol-induced vasorelaxations were investigated in thoracic aorta segments. In addition, the effects of L-cysteine, calindol, and endothelium on H2S generation in mouse aorta segments were investigated.

RESULTS

L-cysteine- and calindol-induced vasorelaxations were reduced in the presence of PAG and Calhex-231. Furthermore, in endothelium-denuded tissues, the vasorelaxations to calindol and L-cysteine were reduced compared to endothelium-intact tissues. Also, calindol increased basal H2S generation, and PAG and Calhex-231 reduced the increase in H2S production stimulated with calindol. Calhex-231 reduced the increase in H2S production in the presence of L-cysteine. Also, H2S production decreased in endothelium-denuded tissues.

CONCLUSION

Endogenous H2S generated by CSE produces endothelium-dependent relaxation by activating CaSR in mouse thoracic aorta tissue.