well as differences due to varying amounts of these catecholamines that are released and sensitivities of various receptors to concentrations. generally, arterial smooth muscle responds to carbon dioxide by producing vasodilation, and responds to oxygen by producing vasoconstriction. pulmonary blood vessels within the lung are unique as they vasodilate to high oxygen tension and vasoconstrict when it falls. bronchiole, smooth muscle that line the airways of the lung, respond to high carbon dioxide producing vasodilation and vasoconstrict when carbon dioxide is low. these responses to carbon dioxide and oxygen by pulmonary blood vessels and bronchiole airway smooth muscle aid in matching perfusion and ventilation within the lungs. further different smooth muscle tissues display extremes of abundant to little sarcoplasmic reticulum so excitation-contraction coupling varies with its dependence on intracellular or extracellular calcium. recent research indicates that sphingosine-1-phosphate (s1p) signaling is an important regulator of vascular smooth muscle contraction. when transmural pressure increases, sphingosine kinase 1 phosphorylates sphingosine to s1p, which binds to the s1p2 receptor in plasma membrane of cells. this leads to a transient increase in intracellular calcium, and activates rac and rhoa signaling pathways. collectively, these serve to increase mlck activity and decrease mlcp activity, promoting muscle contraction. this allows arterioles to increase resistance in response to increased blood pressure and thus maintain constant blood flow. the rhoa and rac portion of the signaling pathway provides a calcium-independent way to regulate resistance artery tone. spread of impulse to maintain organ dimensions against force, cells are fastened to one another by adherens junctions. as a consequence, cells are mechanically coupled to one another such that contraction of one cell invokes some degree of contraction in an adjoining cell. gap junctions couple adjacent cells chemically and electrically, facilitating the spread of chemicals (e.g., calcium) or action potentials between smooth muscle cells. single unit smooth muscle displays numerous gap junctions and these tissues often organize into sheets or bundles which contract in bulk. contraction smooth muscle contraction is caused by the sliding of myosin and actin filaments (a sliding filament mechanism) over each other. the energy for this to happen is provided by the hydrolysis of atp. myosin functions as an atpase utilizing atp to produce a molecular conformational change of part of the myosin and produces movement. movement of the filaments over each other happens when the globular heads protruding from myosin filaments attach and interact with actin filaments to form crossbridges. the myosin heads tilt and drag along the actin filament a small distance (10–12 nm). the heads then release the actin filament and then changes angle to relocate to another site on the actin filament a further distance (10–12 nm) away. they can then re-bind to the actin molecule and drag it along further. this process is called crossbridge cycling and is the same for all muscles (see muscle contraction). unlike cardiac and skeletal muscle, smooth muscle does not contain the calcium-binding protein troponin. contraction is initiated by a calcium-regulated phosphorylation of myosin, rather than a calcium-activated troponin system. crossbridge cycling causes contraction of myosin and actin complexes, in turn causing increased tension along the entire chains of tensile structures, ultimately resulting in contraction of the entire smooth muscle tissue. phasic or tonic smooth muscle may contract phasically with rapid contraction and relaxation, or tonically with slow and sustained contraction. the reproductive, digestive, respiratory, and urinary tracts, skin, eye, and vasculature all contain this tonic muscle type. this type of smooth muscle can maintain force for prolonged time with only little energy utilization. there are differences in the myosin heavy and light chains that also correlate with these differences in contractile patterns and kinetics of contraction between tonic and phasic smooth muscle. activation of myosin heads crossbridge cycling cannot occur until the myosin heads have been activated to allow crossbridges to form. when the light chains are phosphorylated, they become active and will allow contraction to occur. the enzyme that phosphorylates the light chains is called myosin light-chain kinase (mlck), also called mlc20 kinase. in order to control contraction, mlck will work only when the muscle is stimulated to contract. stimulation will increase the intracellular concentration of calcium ions. these bind to a molecule called calmodulin, and form a calcium-calmodulin complex. it is this complex that will bind to mlck to activate it, allowing the chain of reactions for contraction to occur. activation consists of phosphorylation of a serine on position 19 (ser19) on the mlc20 light chain, which causes a conformational change that increases the angle in the neck domain of the myosin heavy chain, which corresponds to the part of the cross-bridge cycle where the myosin head is unattached to the actin filament and relocates to another site on it. after attachment of the myosin head to the actin filament, this serine phosphorylation also activates the atpase activity of the myosin head region to provide the energy to fuel the subsequent contraction. phosphorylation of a threonine on position 18 (thr18) on mlc20 is also possible and may further increase the atpase activity of the myosin complex. sustained maintenance phosphorylation of the mlc20 myosin light chains correlates well with the shortening velocity of smooth muscle. during this period there is a rapid burst of energy utilization as measured by oxygen consumption. within a few minutes of initiation the calcium level markedly decrease, mlc20 myosin light chains phosphorylation decreases, and energy utilization decreases and the muscle can relax. still, smooth muscle has the ability of sustained maintenance of force in this situation as well. this sustained phase has been attributed to certain myosin crossbridges, termed latch-bridges, that are cycling very slowly, notably slowing the progression to the cycle stage whereby dephosphorylated myosin detaches from the actin, thereby maintaining the force at low energy costs. this phenomenon is of great value especially for tonically active smooth muscle. isolated preparations of vascular and visceral smooth muscle contract with depolarizing high potassium balanced saline generating a certain amount of contractile force. the same preparation stimulated in normal balanced saline with an agonist such as endothelin or serotonin will generate more contractile force. this increase in force is termed calcium sensitization. the myosin light chain phosphatase is inhibited to increase the gain or sensitivity of myosin light chain kinase to calcium. there are number of cell signalling pathways believed to regulate this decrease in myosin light chain phosphatase: a rhoa-rock kinase pathway, a protein kinase c-protein kinase c potentiation inhibitor protein 17 (cpi-17) pathway, telokin, and a zip kinase pathway. further rock kinase and zip kinase have been implicated to directly phosphorylate the 20kd myosin light chains. other contractile mechanisms other cell signaling pathways and protein kinases (protein kinase c, rho kinase, zip kinase, focal adhesion kinases) have been implicated as well and actin polymerization dynamics plays a role in force maintenance. while myosin light chain phosphorylation correlates well with shortening velocity, other cell signaling pathways have been implicated in the development of force and maintenance of force. notably the phosphorylation of specific tyrosine residues on the focal adhesion adapter protein-paxillin by specific tyrosine kinases has been demonstrated to be essential to force development and maintenance. for example, cyclic nucleotides can relax arterial smooth muscle without reductions in crossbridge phosphorylation, a process termed force suppression. this process is mediated by the phosphorylation of the small heat shock protein, hsp20, and may prevent phosphorylated myosin heads from interacting with actin. relaxation the phosphorylation of the light chains by mlck is countered by a myosin light-chain phosphatase, which dephosphorylates the mlc20 myosin light chains and thereby inhibits contraction. other signaling pathways have also been implicated in the regulation actin and myosin dynamics. in general, the relaxation of smooth muscle is by cell-signaling pathways that increase the myosin phosphatase activity, decrease the intracellular calcium levels, hyperpolarize the smooth muscle, and/or regulate actin and myosin muscle can be mediated by the endothelium-derived relaxing factor-nitric oxide, endothelial derived hyperpolarizing factor (either an endogenous cannabinoid, cytochrome p450 metabolite, or hydrogen peroxide), or prostacyclin (pgi2). nitric oxide and pgi2 stimulate soluble guanylate cyclase and membrane bound adenylate cyclase, respectively. the cyclic nucleotides (cgmp and camp) produced by these cyclases activate protein kinase g and protein kinase a and phosphorylate a number of proteins. the phosphorylation events lead to a decrease in intracellular calcium (inhibit l type calcium channels, inhibits ip3 receptor channels, stimulates sarcoplasmic reticulum calcium pump atpase), a decrease in the 20kd myosin light chain phosphorylation by altering calcium sensitization and increasing myosin light chain phosphatase activity, a stimulation of calcium sensitive potassium channels which hyperpolarize the cell, and the phosphorylation of amino acid residue serine 16 on the small heat shock protein (hsp20)by protein kinases a and g. the phosphorylation of hsp20 appears to alter actin and focal adhesion dynamics and actin-myosin interaction, and recent evidence indicates that hsp20 binding to 14-3-3 protein is involved in this process. an alternative hypothesis is that phosphorylated hsp20 may also alter the affinity of phosphorylated myosin with actin and inhibit contractility by interfering with crossbridge formation. the endothelium derived hyperpolarizing factor stimulates calcium sensitive potassium channels and/or atp sensitive potassium channels and stimulate potassium efflux which hyperpolarizes the cell and produces relaxation. invertebrate smooth muscle in invertebrate smooth muscle, contraction is initiated with the binding of calcium directly to myosin and then rapidly cycling cross-bridges, generating force. similar to the mechanism of vertebrate smooth muscle, there is a low calcium and low energy utilization catch phase. this sustained phase or catch phase has been attributed to a catch protein that has similarities to myosin light-chain kinase and the elastic protein-titin called twitchin. clams and other bivalve mollusks use this catch phase of smooth muscle to keep their shell closed for prolonged periods with little energy usage. specific effects although the structure and function is basically the same in smooth muscle cells in different organs, their specific effects or end-functions differ. the contractile function of vascular smooth muscle regulates the lumenal diameter of the small arteries-arterioles called resistance arteries, thereby contributing significantly to setting the level of blood pressure and blood flow to vascular beds. smooth muscle contracts slowly and may maintain the contraction (tonically) for prolonged periods in blood vessels, bronchioles, and some sphincters. activating arteriole smooth muscle can decrease the lumenal diameter 1/3 of resting so it drastically alters blood flow and resistance. activation of aortic smooth muscle doesn't significantly alter the lumenal diameter but serves to increase the viscoelasticity of the vascular wall. in the digestive tract, smooth muscle contracts in a rhythmic peristaltic fashion, rhythmically forcing foodstuffs through the digestive tract as the result of phasic contraction. a non-contractile function is seen in specialized smooth muscle within the afferent arteriole of the juxtaglomerular apparatus, which secretes renin in response to osmotic and pressure changes, and also it is believed to secrete atp in tubuloglomerular regulation of glomerular filtration rate. renin in turn activates the renin–angiotensin system to regulate blood pressure. growth and rearrangement the mechanism in which external factors stimulate growth and rearrangement is not yet fully understood. a number of growth factors and neurohumoral agents influence smooth muscle growth and differentiation. the notch receptor and cell-signaling pathway have been demonstrated to be essential to vasculogenesis and the formation of arteries and veins. the proliferation is implicated in the pathogenesis of atherosclerosis and is inhibited by nitric oxide. the embryological origin of smooth muscle is usually of mesodermal origin, after the creation of muscle cells in a process known as myogenesis. however, the smooth muscle within the aorta and pulmonary arteries (the great arteries of the heart) is derived from ectomesenchyme of neural crest origin, although coronary artery smooth muscle is of mesodermal origin. related diseases multisystemic smooth muscle dysfunction syndrome is a genetic condition in which the body of a developing embryo does not create enough smooth muscle for the gastrointestinal system. this condition is fatal. anti-smooth muscle antibodies (asma) can be a symptom of an auto-immune disorder, such as hepatitis, cirrhosis, or lupus. smooth muscle tumors are most commonly benign, and are then called leiomyomas. they can occur in any organ, but they usually occur in the uterus, small bowel, and esophagus. malignant smooth muscle tumors are called leiomyosarcomas. leiomyosarcomas are one of the more common types of soft-tissue sarcomas. vascular smooth muscle tumors are very rare. they can be malignant or benign,