Thapsigargin,A Ca2+-ATPase inhibitor,relaxes rat aorta via nitric oxide formation

Thapsigargin induced endothelium-dependent relaxation and cGMP production in rat thoracic aorta, and these effects were inhibited by nitric oxide (NO) pathway inhibitors, a calmodulin inhibitor and removal of Ca²⁺, suggesting that NO is involved in the thapsigargin-induced relaxation. Thapsigargin may deplete Ca²⁺ stores in the endothelial cells by inhibiting the CA²⁺-ATPase, a Ca²⁺ pump, which in turn triggers influx of extracellular Ca²⁺, leading to activation of constitutive NO synthase and resultant NO generation. The NO thus formed may activate soluble guanylate cyclase to produce cGMP in the vascular smooth muscle.