The role of cGMP/cGKI signalling and Trpc channels in regulation of vascular tone.

摘要: Aims Signalling via cGMP-dependent protein kinase I (cGKI) is the major pathway in vascular smooth muscle (SM), by which endothelial NO regulates tone. Recent evidence suggests that canonical transient receptor potential (Trpc) channels are targets of cGKI SM and mediate relaxant effects cGMP signalling. We tested this concept investigating role cGMP/cGKI signalling on tone peripheral resistance using Trpc 6−/−, 3−/−, 3−/−/ 6 −/−, 1−/−/3−/−/6−/−, SM-specific cGKI−/− (sm-cGKI−/−) mice. Methods results α-Adrenergic stimulation induced similar contractions L-NG-nitroarginine methyl ester (l-NAME)-treated aorta comparably increased pressure hind limbs from all mouse lines investigated. After α-adrenergic stimulation, 8-Br-cGMP diminished similarly aortic control, 3−/−/6−/−, 1−/−/3−/−/6−/− mice but not sm-cGKI−/− mice. In untreated aorta, control 3−/− larger sm-cGKI−/−, mice, indicating a functional link between Trpc6 channels. Trpc3 were detected immunocytochemistry both isolated cells (SMCs) (ECs), whereas only ECs. Phenylephrine-stimulated Ca2+ levels SMCs (Ctr) −/− Carbachol-stimulated reduced ECs Stimulated lowered Ctr Trpc6−/− ECs. Conclusions The suggest Trpc1,3,6 functionally coupled SM. Deletion impaired vasodilator aorta.