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. Author manuscript; available in PMC: 2014 Mar 1.
Published in final edited form as: J Cardiovasc Pharmacol. 2013 Mar;61(3):176–187. doi: 10.1097/FJC.0b013e31828165db

Figure 5.

Figure 5

Co-release of constitutive (c) and inducible (i) EDHFs mediate synergistic vasorelaxation. In vascular endothelial cells, acetylcholine activates; 1) calcium influx which stimulates IKCa and SKCa channels resulting in K ion efflux (the cEDHF pathway) and 2) PLA2 release of AA from membrane phospholipids. AA is metabolized by 15-LO-1 to HEETA and THETA (the iEDHF pathway). 15-LO-1 expression is increased by hypoxia, hypercholesterolemia, interleukin-4 (IL-4), interleukin-13 (IL-13), estrogen and anemia. The cEDHF and iEDHF pathways cause smooth muscle hyperpolarization via distinct synergistic mechanisms. For the cEDHF pathway, endothelial cell hyperpolarization from K ion efflux is transmitted to the smooth muscle through myoendothelial gap junctions or K ions activate smooth muscle KIR channels and the Na/K ATPase. HEETAs and THEETAs from the iEDHF pathway activate smooth muscle SKCa channels.