Role of cGMP signals in tetramethylpyrazine induced relaxation of the isolated rat aortic strip

Abstract In the present study, role of guanosine-3′,5′-cyclic monophosphate (cGMP) in the vasodilatation of tetramethylpyrazine (TMP), one of the active ingredients of the Chinese herb Chuang-xion , was investigated. We found that the TMP could decrease the vascular tone of isolated rat aorta precontracted with phenylephrine (10 − 8 M) in a concentration-dependent manner from 10 − 5 M to 10 − 3 M. Also, the TMP-induced relaxation was reduced by 1H-(1,2,4)-oxadiazol-(4,3-a)-quinoxalin-1-one (ODQ) or methylene blue, the inhibitor of soluble guanylyl cyclase. Moreover, the vasodilative response to TMP was enhanced significantly in the presence of sildenafil, a well-known inhibitor of phosphodiestrase type 5 that is sensitive to cGMP. In addition, TMP could increase the cGMP level in the isolated aortic rings and TMP-induced vasodilatation was deleted by cGMP-dependent protein kinases (PKG) blockade. These results suggest that relaxation of rat aortic strip by TMP is induced in the cGMP-dependent manner.