Evidence for functional coupling of cGMP/cGKI signalling and TRPC channels in endothelium but not in vascular smooth muscle

Background Signaling via cGMP-dependent protein kinase I (cGKI) is the major pathway in vascular smooth muscle (SM), by which endothelial NO regulates vascular tone. Recent evidence suggests that canonical transient receptor potential (TRPC) channels are targets of cGKI in SM and mediate the relaxant effects of cGMP signaling. We tested this concept by investigating the role of cGMP/cGKI signaling on vascular tone and peripheral resistance using Trpc6, Trpc3, Trpc3/6, Trpc1/3/6, and SM-specific cGKI (sm-cGKI) mice.