Thesis (Ph.D.)--Chulalongkorn University, 2008

It has been reported that depletion of GSH affected the function of vascular system, including control of vascular tone. This study investigated the direct effects of GSH on vascular tension, using the in vitro model of isolated rat thoracic aorta. The results showed that GSH significantly induced both endothelium-dependent and endothelium-independent relaxation of aortic preparations which were precontracted with PE. However, the presence of endothelium influenced the response of aortic muscles toward treatment of GSH, resulting in the difference of the characteristic of the tracing profiles and degree of relaxation. The endothelium-dependent relaxation were abolished by pretreatment with L-NAME, methylene blue and glibenclamide whereas the endothelium-independent relaxation were reduced only by pretreatment with glibenclamide. Therefore, the mechanisms of GSH-induced relaxation involved the NOcGMP pathway as well as membrane hyperpolarization pathway. Moreover, extracellular Ca2+ could also determine the effects of GSH on vasorelaxation because the presence of EGTA, but not BAPTA-AM, could interfere the vasorelaxation. In addition, GSH was able to enhance the effects of Ach, but not SNP on vasorelaxation. Hence, it was likely that GSH enhanced the production of NO via increasing Ca2+ influx in endothelium cell, but had no effect on the production of cGMP in vascular smooth muscle cell. Furthermore, GSH was able to directly inhibit the contraction of smooth muscle in certain conditions. The results showed that GSH could elicit its inhibitory action toward the contraction induced by PE, 5-HT and histamine but not those induced by KCl, TEA and PMA. In addition, GSH also inhibited the Ca2+ influx in high K+-depolarizing solution. Thus, these findings suggested that GSH modulated the vascular tone via interference of Ca2+ influx through membrane Ca2+ channels on vascular smooth cells. Moreover, GSH could partially interfere Ca2+-release from internal storage which coupled to IP3 signaling. Taken together, GSH could directly modulate the control of vascular tone by enhance the NO-cGMP pathway in endothelium cells as well as disrupt the Ca2+ influx and Ca2+- release in the smooth muscle cells.