Vasodilation produced by the direct effects of caffeine on the VSMC. Caffeine inhibits the voltage-dependent Ca2+ channels and the entrance of calcium to the cytoplasm. In addition, it inhibits the IP3 receptor and increases the “non-contractile Ca2+. Due to its antiphosphodiesterase action, there is an accumulation of cAMP, which increases the non-contractile Ca2+, diminishes cytoplasmic Ca2+ (iCa2+), and inhibits Myosin Light Chain Kinase (MLC Kinase). Therefore MLC phosphatase predominates and there is vasodilation. Caffeine also directly inhibits MLC Kinase and the actin-myosin interaction.