**3.3 NO-induced muscle relaxation through Ca2+ signaling**

To fully understand how NO causes vasodilation, it is necessary to perceive the relationship between NO-cGMP pathway and [Ca2+]i. At rest, extracellular Ca2+ concentration is high (1–2 mM), while the cytosolic Ca2+ is over 1000 times lower (>1 μM) [40, 41]. In the endoplasmic reticulum (ER, or SR in cardiac muscles), Ca2+ concentration is also high (about 400 μM) [40]. NO modulates [Ca2+]i by controlling Ca2+ exchange mechanisms on both cell and SR membranes.
