Thapsigargin induces an endothelium-dependent, intracellular calcium ion-dependent vasodilation in vitro

The effect of thapsigargin, a specific inhibitor of intracellular Ca(2+)-ATPases, on endothelium-dependent relaxation was studied in the guinea pig thoracic aorta. Thapsigargin (1 nM-1 microM) produced a concentration-dependent relaxation of aortic strips precontracted by phenylephrine (0.1 microM) in the presence and absence of extracellular Ca2+. Thapsigargin (0.1 microM-10 microM) produced the concentration-dependent contraction in aortic strips with no endothelium in the presence and absence of extracellular Ca2+. The relaxant effect of thapsigargin (1 microM) was not attained in a de-endothelialised aortic strip. NG-nitro-L-arginine (10 nM-0.1 mM), a blocker of NO synthase, produced a concentration-dependent inhibition of thapsigargin-induced relaxation. Thapsigargin failed to produce vasodilation by pretreatment of aortic strips with NG-nitro-L-arginine (10 microM). Thapsigargin (1 microM) increased tissue levels of guanosine 3', 5' cyclic-monophosphate in aortic strips preincubated with phenylephrine (0.1 microM). The results suggest that the intracellular Ca2+ mobilization in endothelial cells by thapsigargin is of significance in the endothelium-dependent relaxation of guinea pig thoracic aorta.