The Role of Rho and Rho-Dependent Kinase in Serotonin-Induced Contraction Observed in Bovine Middle Cerebral Artery

Nishikawa, Yasumasa; Doi, Mamoru; Koji, Takahiro; Watanabe, Mikio; Kimura, Shuichi; Kawasaki, Satoshi; Sasaki, Kazuhiko

doi:10.1620/tjem.201.239

Cited by 14 publications

(12 citation statements)

References 31 publications

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“…Relatively few studies have examined the functional importance of Rho-kinase in cerebral circulation, but recent evidence suggests that this signaling pathway mediates vasoconstrictor responses to serotonin, endothelin-1, UTP, and oxyhemoglobin (Miao et al, 2002;Nishikawa et al, 2003;Wickman et al, 2003;Luykenaar et al, 2004).…”

Section: Constrictor Responses Of Cerebral Arteries To Angiotensin IImentioning

confidence: 99%

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Cerebral Vascular Effects of Angiotensin II: New Insights from Genetic Models

Faraci

Lamping

Modrick

et al. 2005

J Cereb Blood Flow Metab

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Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT 1A receptors and Rho-kinase. Basilar arteries (baseline diameter B130 lm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by B85% in mice deficient in expression of AT 1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R þ ) and angiotensinogen (A þ ). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R þ A þ mice (Po0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R þ A þ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R þ A þ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT 1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.

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Section: Constrictor Responses Of Cerebral Arteries To Angiotensin IImentioning

confidence: 99%

“…Second, we examined the role of Rho-kinase in mediating vasoconstriction in response to Ang II. Activation of Rho-kinase is thought to be a key mechanism of calcium sensitization that mediates responses to several vasoconstrictors (Miao et al, 2002;Nishikawa et al, 2003;Wickman et al, 2003;Luykenaar et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Cerebral Vascular Effects of Angiotensin II: New Insights from Genetic Models

Faraci

Lamping

Modrick

et al. 2005

J Cereb Blood Flow Metab

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“…20 Another study suggested the activation of Rho A and ROCK in 5-HT-induced contraction of the bovine middle cerebral artery. 21 Serotonin participates in pulmonary hypertension, 5,22,23 and a polymorphism of the 5-HT transporter has been proposed to be involved in pulmonary hypertension in humans. 24 Because agents that block ROCK are currently available 25,26 and may be useful in pulmonary hypertension, [27][28][29] we have undertaken an investigation of the potential participation of ROCK in pulmonary arterial SMC signaling and proliferation produced by 5-HT.…”

mentioning

confidence: 99%

Rho Kinase–Induced Nuclear Translocation of ERK1/ERK2 in Smooth Muscle Cell Mitogenesis Caused by Serotonin

Liu

Suzuki

Day

et al. 2004

Circulation Research

178

160

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Abstract-There is now considerable evidence supporting a mitogenic action of serotonin (5-HT) on vascular smooth muscle cells (SMC) that might participate in pulmonary hypertension (PH). Our previous studies have demonstrated that 5-HT-induced proliferation depends on the generation of reactive oxygen species and activation of extracellular signal-regulated kinase (ERK) 1/ERK2. Activation of Rho kinase (ROCK) in SMC also may be important in PH. We undertook the present study to assess the role of Rho A/ROCK and its possible relation to ERK1/ERK2 in 5-HT-induced pulmonary artery SMC proliferation. We found that this stimulation of SMC proliferation requires Rho A/ROCK as inhibition with Y27632, a ROCK inhibitor, or dominant negative (DN) mutant Rho A blocks 5-HT-induced proliferation, cyclin D1 expression, phosphorylation of Elk, and the DNA binding of transcription factors, Egr-1 and GATA-4. 5-HT activated ROCK, and the activation was blocked by GR 55562 and GR127935, 5-HT 1B/1D receptor antagonists, but not by serotonin transport ( Key Words: smooth muscle cells Ⅲ serotonin Ⅲ Rho kinase Ⅲ ERK1/ERK2 Ⅲ pulmonary hypertension I n addition to its actions as a vasoconstrictor and neurotransmitter, serotonin (5-HT) is now recognized to be a cellular mitogen. [1][2][3] There is evidence that this mitogenic action is initiated by active transport via a cell surface transporter (SERT) of bovine, rat, and human pulmonary vascular smooth muscle cells (SMC). 1,4 -6 For other cells, the mitogenic action might be started through 1 or more of the cell surface receptors for 5-HT. A hierarchy of cell signaling responses occurs subsequent to ligation of the cell surface transporter or receptor. It has been well-established that these signaling responses include sequential activations of the small GTPase coupled protein, Rac-1, NADPH oxidase producing superoxide that is dismutated to H 2 O 2 , and extracellular signal-regulated kinase (ERK) 1/ERK2 MAP kinase. 2,[7][8][9] The small GTPase Rho A and its effector, Rho kinase (ROCK), also participate in cellular stress fiber formation and cell cycle progression. 10 -19 There has been limited study of the relationship of Rho A and ROCK to 5-HT. One study showed that Rho A bound to GTP is elevated in the rabbit aortic vascular ring preparation treated with 5-HT. 20 Another study suggested the activation of Rho A and ROCK in 5-HT-induced contraction of the bovine middle cerebral artery. 21 Serotonin participates in pulmonary hypertension, 5,22,23 and a polymorphism of the 5-HT transporter has been proposed to be involved in pulmonary hypertension in humans. 24 Because agents that block ROCK are currently available 25,26 and may be useful in pulmonary hypertension, 27-29 we have undertaken an investigation of the potential participation of ROCK in pulmonary arterial SMC signaling and proliferation produced by 5-HT. The results of our study show that ROCK is activated by 5-HT and that its activation is essential for SMC proliferation produced by 5-HT. Furthermore, with the use of a chemi...

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“…For example, activity of rho kinase is thought to be a key mediator of vasoconstrictor responses through effects on calcium sensitization. [17][18][19] Activity of rho kinase may be increased in cerebral blood vessels during disease. 8,20 The precise cause for this increase is not certain but may be a consequence of loss of inhibitory effects of NO on rho kinase or direct effects of ROS to promote activity of rho kinase.…”

mentioning

confidence: 99%

Oxidative Stress

Faraci

2005

Stroke

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The Role of Rho and Rho-Dependent Kinase in Serotonin-Induced Contraction Observed in Bovine Middle Cerebral Artery

Cited by 14 publications

References 31 publications

Cerebral Vascular Effects of Angiotensin II: New Insights from Genetic Models

Cerebral Vascular Effects of Angiotensin II: New Insights from Genetic Models

Rho Kinase–Induced Nuclear Translocation of ERK1/ERK2 in Smooth Muscle Cell Mitogenesis Caused by Serotonin

Oxidative Stress

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