Nitric oxide and protein kinase G act on TRPC1 to inhibit 11,12-EET-induced vascular relaxation

Aims Vascular endothelial cells synthesize and release vasodilators such as nitric oxide (NO) and epoxyeicosatrienoic acids (EETs). NO is known to inhibit EET-induced smooth muscle hyperpolarization and relaxation. This study investigates the underlying mechanism of this inhibition. Methods and results Throughmeasurements ofmembrane potential and arterial tension, we show that 11,12-EET inducedmembrane hyper-polarization and vascular relaxation in endothelium-denuded porcine coronary arteries. These responses were sup-pressed by S-nitroso-N-acetylpenicillamine (SNAP) and 8-Br-cGMP, an NO donor and a membrane-permeant analogueof cGMP, respectively. The inhibitoryactionsof SNAPand8-Br-cGMPon11,12-EET-inducedmembranehyper-polarization and vascular relaxation were reversed by hydroxocobalamin, an NO scavenger; ODQ, a guanylyl cyclase inhibitor; and KT5823, a protein kinase G (PKG) inhibitor. The inhibitory actions of SNAP and 8-bromo cyclic GM