Ca²⁺ signaling induces gene transcription and mediates cellular functions in diverse types of cells. In neurons, Ca²⁺ influx through voltage-dependent Ca²⁺ channels (VDCC) activates Ca²⁺/calmodulin-dependent protein kinases (CaMK), promotes gene transcription and constructs neural networks. This pathway is called excitation-transcription (E-T) coupling. E-T coupling is also reported in vascular smooth muscle cells (VSMC), but its molecular mechanisms and pathophysiological roles are unknown. In VSMCs, caveolin (cav)-1, an essential component of caveolae, forms Ca²⁺ microdomains where VDCC and its effectors are accumulated and regulates vascular tone. In the present study, we hypothesized that prolonged VDCC activation in caveolae triggers E-T coupling in VSMC and causes vascular remodeling. When the mesenteric artery was depolarized for longer than 30 min, nuclear CREB phosphorylation and pro-inflammatory gene transcription were promoted. These responses were significantly reduced in cav-1 KO mice. Pharmacological inhibition or siRNA knockdown of CaMKK-CaMK pathway revealed the molecular pathway connecting Ca²⁺ influx through VDCC in caveolae and CREB phosphorylation. These results suggest that excessive Ca²⁺ signaling in caveolae causes E-T coupling in VSMC and triggers vascular remodeling by upregulating pro-inflammatory genes.