KEGG   PATHWAY: rno04270
Entry
rno04270                    Pathway                                
Name
Vascular smooth muscle contraction - Rattus norvegicus (rat)
Description
The vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regulate the blood flow and pressure.
The principal mechanisms that regulate the contractile state of VSMCs are changes in cytosolic Ca2+ concentration ([Ca2+]c). In response to vasoconstrictor stimuli, Ca2+ is mobilized from intracellular stores and/or the extracellular space to increase [Ca2+]c in VSMCs. The increase in [Ca2+]c, in turn, activates the Ca2+-CaM-MLCK pathway and stimulates MLC20 phosphorylation, leading to myosin-actin interactions and, hence, the development of contractile force. The sensitivity of contractile myofilaments or MLC20 phosphorylation to Ca2+ can be secondarily modulated by other signaling pathways. During receptor stimulation, the contractile force is greatly enhanced by the inhibition of myosin phosphatase. Rho/Rho kinase, PKC, and arachidonic acid have been proposed to play a pivotal role in this enhancement.
The signaling events that mediate relaxation include the removal of a contractile agonist (passive relaxation) and activation of cyclic nucleotide-dependent signaling pathways in the continued presence of a contractile agonist (active relaxation). Active relaxation occurs through the inhibition of both Ca2+ mobilization and myofilament Ca2+ sensitivity in VSMCs.
Class
Organismal Systems; Circulatory system
Pathway map
rno04270  Vascular smooth muscle contraction
rno04270

Other DBs
GO: 0014829
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
29412  Adra1a; alpha-1A adrenergic receptor [KO:K04135]
24173  Adra1b; alpha-1B adrenergic receptor [KO:K04136]
29413  Adra1d; alpha-1D adrenergic receptor [KO:K04137]
24179  Agt; angiotensinogen precursor [KO:K09821]
24180  Agtr1a; type-1 angiotensin II receptor A [KO:K04166]
81638  Agtr1b; type-1 angiotensin II receptor B [KO:K04166]
24323  Edn1; endothelin-1 preproprotein [KO:K16366]
24324  Edn2; endothelin-2 precursor [KO:K16367]
366270  Edn3; endothelin-3 precursor [KO:K05227]
24326  Ednra; endothelin-1 receptor precursor [KO:K04197]
24221  Avp; vasopressin-neurophysin 2-copeptin preproprotein [KO:K05242]
25107  Avpr1a; vasopressin V1a receptor [KO:K04226]
100909648  Avpr1b; vasopressin V1b receptor [KO:K04227]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
81662  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
29354  Pla2g5; phospholipase A2 group V precursor [KO:K01047] [EC:3.1.1.4]
29359  Pla2g10; group 10 secretory phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
29387  Pla2g2c; group IIC secretory phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
29526  Pla2g1b; phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
29692  Pla2g2a; phospholipase A2, membrane associated precursor [KO:K01047] [EC:3.1.1.4]
289733  Pla2g3; group 3 secretory phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
367415  Pla2g12b; group XIIB secretory phospholipase A2-like protein isoform X2 [KO:K01047] [EC:3.1.1.4]
298579  Pla2g2d; group IID secretory phospholipase A2 precursor [KO:K01047] [EC:3.1.1.4]
690388  Pla2g2f; group IIF secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
296091  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
24653  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
311341  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
691905  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
691907  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
691810  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
360426  Pla2g6; 85/88 kDa calcium-independent phospholipase A2 isoform 1 [KO:K16343] [EC:3.1.1.4]
298423  Cyp4a3; cytochrome P450 4A14 [KO:K07425] [EC:1.14.14.80]
50549  Cyp4a1; cytochrome P450 4A10 [KO:K07425] [EC:1.14.14.80]
266674  Cyp4a8; cytochrome P450 4A12 [KO:K07425] [EC:1.14.14.80]
120102953  Cyp4a2l1; cytochrome P450, family 4, subfamily a, polypeptide 2 like 1 [KO:K07425] [EC:1.14.14.80]
24306  Cyp4a2; cytochrome P450 4A2 [KO:K07425] [EC:1.14.14.80]
83731  Kcnma1; calcium-activated potassium channel subunit alpha-1 isoform 1 [KO:K04936]
680912  Kcnu1; potassium channel subfamily U member 1 isoform X6 [KO:K05274]
29747  Kcnmb1; calcium-activated potassium channel subunit beta-1 [KO:K04937]
294961  Kcnmb2; calcium-activated potassium channel subunit beta-2 [KO:K04938]
310303  Kcnmb3; calcium-activated potassium channel subunit beta-3 [KO:K04939]
66016  Kcnmb4; calcium-activated potassium channel subunit beta-4 [KO:K04941]
24239  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
29716  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
114493  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
682930  Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
50663  Calm2; calmodulin-2 [KO:K02183]
288057  Mylk; myosin light chain kinase, smooth muscle [KO:K00907] [EC:2.7.11.18]
117558  Mylk2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
291926  Mylk3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
100911165  Mylk4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
685867  Myl6; myosin light polypeptide 6 [KO:K12751]
304447  RGD1559821; myosin light polypeptide 6-like [KO:K12751]
102551071  myosin light polypeptide 6-like [KO:K12751]
296313  Myl9; myosin regulatory light polypeptide 9 [KO:K12755]
25745  Myh9; myosin-9 [KO:K10352]
308572  Myh14; myosin-14 [KO:K10352]
79433  Myh10; myosin-10 [KO:K10352]
24582  Myh11; myosin-11 [KO:K10352]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
170538  Prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
29340  Prkce; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
81749  Prkch; protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
85420  Prkcq; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
64363  Araf; serine/threonine-protein kinase A-Raf isoform 1 [KO:K08845] [EC:2.7.11.1]
114486  Braf; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
25687  Cald1; non-muscle caldesmon isoform 2 [KO:K12327]
81633  Acta2; actin, aortic smooth muscle [KO:K12313]
25365  Actg2; actin, gamma-enteric smooth muscle [KO:K12315]
114004  Ppp1r14a; protein phosphatase 1 regulatory subunit 14A [KO:K12328]
24668  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
24669  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform 1 [KO:K06269] [EC:3.1.3.16]
25594  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
116670  Ppp1r12a; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
304813  Ppp1r12b; protein phosphatase 1 regulatory subunit 12B [KO:K12329]
499076  Ppp1r12c; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
81663  Gna12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
303634  Gna13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
367072  Arhgef12; rho guanine nucleotide exchange factor 12 [KO:K07532]
60323  Arhgef1; rho guanine nucleotide exchange factor 1 [KO:K12330]
78966  Arhgef11; rho guanine nucleotide exchange factor 11 [KO:K12331]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
81762  Rock1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
25537  Rock2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
25369  Adora2a; adenosine receptor A2a A2AR [KO:K04266]
29316  Adora2b; adenosine receptor A2b [KO:K04267]
292661  Ptgir; prostacyclin receptor [KO:K04263]
24241  Calca; calcitonin gene-related peptide 1 isoform Cgrp preproprotein [KO:K12332]
171519  Calcb; calcitonin gene-related peptide 2 [KO:K12332]
25026  Adm; pro-adrenomedullin precursor [KO:K12333]
399475  Adm2; protein ADM2 preproprotein [KO:K25343]
25029  Calcrl; calcitonin gene-related peptide type 1 receptor precursor [KO:K04577]
58965  Ramp1; receptor activity-modifying protein 1 precursor [KO:K08447]
58966  Ramp2; receptor activity-modifying protein 2 precursor [KO:K08448]
56820  Ramp3; receptor activity-modifying protein 3 precursor [KO:K08449]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
24602  Nppa; natriuretic peptides A precursor [KO:K12334]
25105  Nppb; natriuretic peptides B precursor [KO:K12335]
24603  Npr1; atrial natriuretic peptide receptor 1 precursor [KO:K12323] [EC:4.6.1.2]
114593  Nppc; C-type natriuretic peptide precursor [KO:K12336]
116564  Npr2; atrial natriuretic peptide receptor 2 precursor [KO:K12324] [EC:4.6.1.2]
54286  Prkg1; cGMP-dependent protein kinase 1 [KO:K07376] [EC:2.7.11.12]
308899  Irag1; inositol 1,4,5-triphosphate receptor associated 1 isoform b [KO:K12337]
66012  Gucy1a2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
497757  Gucy1a1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
25206  Gucy1b2; guanylate cyclase soluble subunit beta-2 isoform 2 [KO:K12319] [EC:4.6.1.2]
25202  Gucy1b1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00212  Adenosine
C00219  Arachidonate
C00238  Potassium cation
C00533  Nitric oxide
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00942  3',5'-Cyclic GMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01312  Prostaglandin I2
C14748  20-HETE
C14768  5,6-EET
C14769  8,9-EET
C14770  11,12-EET
C14771  14,15-EET
Reference
PMID:17458653
  Authors
Akata T
  Title
Cellular and molecular mechanisms regulating vascular tone. Part 2: regulatory mechanisms modulating Ca2+ mobilization and/or myofilament Ca2+ sensitivity in vascular smooth muscle cells.
  Journal
J Anesth 21:232-42 (2007)
DOI:10.1007/s00540-006-0488-4
Reference
PMID:12689814
  Authors
Ogut O, Brozovich FV
  Title
Regulation of force in vascular smooth muscle.
  Journal
J Mol Cell Cardiol 35:347-55 (2003)
DOI:10.1016/S0022-2828(03)00045-2
Reference
PMID:16339747
  Authors
Hilgers RH, Webb RC
  Title
Molecular aspects of arterial smooth muscle contraction: focus on Rho.
  Journal
Exp Biol Med (Maywood) 230:829-35 (2005)
DOI:10.1177/153537020523001107
Reference
PMID:12693609
  Authors
Schlossmann J, Feil R, Hofmann F
  Title
Signaling through NO and cGMP-dependent protein kinases.
  Journal
Ann Med 35:21-7 (2003)
DOI:10.1080/07853890310004093
Reference
PMID:16870827
  Authors
Mehta PK, Griendling KK
  Title
Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.
  Journal
Am J Physiol Cell Physiol 292:C82-97 (2007)
DOI:10.1152/ajpcell.00287.2006
Reference
PMID:19120701
  Authors
Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG
  Title
Smooth muscle signalling pathways in health and disease.
  Journal
J Cell Mol Med 12:2165-80 (2008)
DOI:10.1111/j.1582-4934.2008.00552.x
Reference
PMID:11165670
  Authors
Fukata Y, Amano M, Kaibuchi K
  Title
Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.
  Journal
Trends Pharmacol Sci 22:32-9 (2001)
DOI:10.1016/S0165-6147(00)01596-0
Reference
PMID:17158339
  Authors
Dimopoulos GJ, Semba S, Kitazawa K, Eto M, Kitazawa T
  Title
Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle.
  Journal
Circ Res 100:121-9 (2007)
DOI:10.1161/01.RES.0000253902.90489.df
Reference
PMID:17200683
  Authors
Hynynen MM, Khalil RA
  Title
The vascular endothelin system in hypertension--recent patents and discoveries.
  Journal
Recent Pat Cardiovasc Drug Discov 1:95-108 (2006)
DOI:10.2174/157489006775244263
Reference
PMID:15269340
  Authors
Brain SD, Grant AD
  Title
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
  Journal
Physiol Rev 84:903-34 (2004)
DOI:10.1152/physrev.00037.2003
Reference
PMID:11773611
  Authors
Roman RJ
  Title
P-450 metabolites of arachidonic acid in the control of cardiovascular function.
  Journal
Physiol Rev 82:131-85 (2002)
DOI:10.1152/physrev.00021.2001
Reference
PMID:18040024
  Authors
Surks HK
  Title
cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two isoforms.
  Journal
Circ Res 101:1078-80 (2007)
DOI:10.1161/CIRCRESAHA.107.165779
Reference
PMID:15026027
  Authors
Vanhoutte PM
  Title
Endothelium-dependent hyperpolarizations: the history.
  Journal
Pharmacol Res 49:503-8 (2004)
DOI:10.1016/j.phrs.2003.11.015
Reference
PMID:10221985
  Authors
Davis MJ, Hill MA
  Title
Signaling mechanisms underlying the vascular myogenic response.
  Journal
Physiol Rev 79:387-423 (1999)
DOI:10.1152/physrev.1999.79.2.387
Reference
PMID:11679404
  Authors
Fleming I.
  Title
Cytochrome p450 and vascular homeostasis.
  Journal
Circ Res 89:753-62 (2001)
DOI:10.1161/hh2101.099268
Reference
PMID:10911373
  Authors
Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP
  Title
Molecular mechanism of cGMP-mediated smooth muscle relaxation.
  Journal
J Cell Physiol 184:409-20 (2000)
DOI:10.1002/1097-4652(200009)184:3<409::AID-JCP16>3.0.CO;2-K
Reference
PMID:18552454
  Authors
Ko EA, Han J, Jung ID, Park WS
  Title
Physiological roles of K+ channels in vascular smooth muscle cells.
  Journal
J Smooth Muscle Res 44:65-81 (2008)
DOI:10.1540/jsmr.44.65
Reference
PMID:18703404
  Authors
Woodard GE, Rosado JA
  Title
Natriuretic peptides in vascular physiology and pathology.
  Journal
Int Rev Cell Mol Biol 268:59-93 (2008)
DOI:10.1016/S1937-6448(08)00803-4
Reference
PMID:11709400
  Authors
Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG
  Title
Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide.
  Journal
Am J Physiol Heart Circ Physiol 281:H2337-65 (2001)
DOI:10.1152/ajpheart.2001.281.6.H2337
Reference
PMID:15725705
  Authors
Hirano K, Hirano M, Kanaide H
  Title
Regulation of myosin phosphorylation and myofilament Ca2+ sensitivity in vascular smooth muscle.
  Journal
J Smooth Muscle Res 40:219-36 (2004)
DOI:10.1540/jsmr.40.219
Reference
PMID:9458738
  Authors
Freeman EJ, Ruehr ML, Dorman RV
  Title
ANG II-induced translocation of cytosolic PLA2 to the nucleus in vascular smooth muscle cells.
  Journal
Am J Physiol 274:C282-8 (1998)
DOI:10.1152/ajpcell.1998.274.1.C282
Reference
PMID:12060106
  Authors
Murphy TV, Spurrell BE, Hill MA
  Title
Cellular signalling in arteriolar myogenic constriction: involvement of tyrosine phosphorylation pathways.
  Journal
Clin Exp Pharmacol Physiol 29:612-9 (2002)
DOI:10.1046/j.1440-1681.2002.03698.x
Related
pathway
rno00590  Arachidonic acid metabolism
rno04020  Calcium signaling pathway
KO pathway
ko04270   
LinkDB

DBGET integrated database retrieval system