The role of cytosolic Ca2+ and cyclic GMP on endothelin-3 in rat aorta
ABSTRACT: The role of
cytosolic Ca2+ and cyclic GMP on
endothelin-3 (ET-3) induced vasorelaxation in rat aorta were investigated. ET-3
induced transient increased in cytosolic Ca2+ [Ca2+]i and cyclic GMP
accompanied by transient vasorelaxation in aortic strips precontracted with 100
nM norepinephrine. An inhibitor of nitric oxide synthase, 100 µM NG-monomethyl-L-arginine(L-NMMA),
abolished completely the increase in cyclyc GMP and the relaxant effect but not
the increase in endothelial [Ca2+]i of ET-3. In the absence ofthe endothelium
or in the presence of an antagonist of ETB receptors, 3
µM IRL 1038 almost completely inhibited [Ca2+]i increase, cyclic GMP
increase, and vasorelaxation induced by ET-3 whereas pretreatment with an ETA receptor
antagonist, 3 µM BQ 123 did not change
the increase [Ca2+]i, increase cyclic GMP and relaxation induced by ET-3. These
results suggest that ET-3 acts on ETB receptors in the vascular endothelium to
increase [Ca2+]I and the production of
nitric oxid in the endothelium. Nitric oxide, in turn, stimulates guanylate
cyclase to increase production of cyclic GMP leading to relaxation of the
aorta.
Author: Sri Agus Sudjarwo
Journal Code: jpkedokterangg050005
