It may be possible that, for example, peroxynitrite formation by Sin-1 does not reach the deeper smooth muscle cell layers when applied ex vivo, but that intrinsic formation of NO and superoxide radical by in vivo arterial hypertension generates enough intracellular peroxynitrite to cause the necessary oxidative damage in the smooth muscle cells that leads to impaired nitrite-response. Here, MAPKAP1 is linked to Hypertension.