Regulation of vascular smooth muscle contraction. The roles of Ca2+, protein kinase C and myosin light chain phosphatase.

Vasoconstrictors bind to their receptors on the cell surface to active phospholipase C and Ca2+ channels, resulting in the mobilization of Ca2+ from intracellular are extracellular Ca2+ pools and protein kinase C activation. Vasoconstrictors are also thought to activate a distinct cellular mechanism for downregulating 20 kDa myosin light chain (MLC20) phosphatase activity, which involves Rho p21 and protein kinase C, resulting in an increase in the Ca2+ sensitivity of MLC20 phosphorylation. Protein kinase C also appears to activate a MLC20 phosphorylation-independent mechanism for contraction, contributing to the maintenance of agonist-induced contraction. On the other hand, vasorelaxants inhibit activation of phospholipase C and gating of Ca2+ channels, or stimulate Ca2+ extrusion across the plasma membrane, leading to a decrease in the [Ca2+]i. Vasorelaxants also appear to stimulate MLC20 phosphatase activity, resulting in a further reduction of contractile response. The modulatory mechanism for changing the Ca2+ sensitivity, together with the major regulatory mechanism for cellular Ca2+ metabolism, plays an important role in regulating vascular smooth muscle tone.