The main function of vascular smooth muscle tissue is the regulation o
f blood pressure through changes in the vascular tone. Two main factor
s regulate the contraction and relaxation of vascular smooth muscle ce
lls: the cytosolic free Ca2+ concentration ([Ca2+](i)) and the Ca2+ se
nsitivity of the contractile elements. Schematically, constrictors inc
rease [Ca2+](i) and the Ca2+ sensitivity of contractile apparatus whil
e relaxant agonists have opposite effects, The sources of Ca2+ are bot
h extracellular and intracellular. The sarcoplasmic reticulum (SR) is
the physiological intracellular source of Ca2+. The Ca2+ storage capac
ity of SR involves intraluminal Ca2+ binding protein such as calseques
trin and calreticulin. Ca2+ is released from SR to the cytosol through
InsP(3) and ryanodine receptors (InsP(3)-induced Ca2+ release and Ca2
+-induced Ca2+ release), During relaxation, the [Ca2+], is reduced in
part by Ca2+ pumping into the Sn by Ca2+-ATPase (SERCA). Several isofo
rms of SERCA are expressed in vascular smooth muscle, Ca2+ enters into
vascular smooth cells through Ca2+ permeable ion channels. The capaci
tative Ca2+ entry and ligand-gated channels (P-2 kappa-purinoceptors)
allow extracellular Ca2+ to flow into the cytosol. However, voltage-de
pendent Ca2+ channels represent the main route for Ca2+ entry which is
essentially modulated by the membrane potential. Ca2+-activated chann
els such as Cl- (Cl-Ca) or K+ (K-ca) channels play a key role in the m
odulation of membrane potential. Activated Cl-cd channels depolarize w
hereas activated K-ca channels hyperpolarize the membrane thus causing
increase and decrease in the vascular tone, respectively, Modulation
of the force at constant [Ca2+](i) results from charges in the activit
ies of kinases and phosphatases, acting on the regulatory light chain
of myosin (MLC20) phosphorylation. Intracellular messengers such as ar
achidonic acid or protein kinase modulate the activity of the MLC20 ph
osphatase and thus, the Ca2+ sensitivity. G protein-coupled Ca2+ sensi
tization also involves inhibition of the MLC20 phosphatase. Trimeric a
s well as monomeric G proteins (Rho p(21), Ras p(21)) seem to be respo
nsible for this mechanism. Recent studies, by identifying new regulato
ry mechanisms, provide a better understanding of the funda mental mech
anisms regulating contractile properties of vascular smooth muscle and
open new way for the treatment of vascular diseases.