Angiotensin II-mediated vascular smooth muscle cell growth signaling

Inagami, Tadashi; Eguchi, Satoru

doi:10.1590/s0100-879x2000000600002

Cited by 20 publications

(9 citation statements)

References 29 publications

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“…Increases in pERK1/2 confirmed that WNK3 knockout mice do not lack the AngII response in aorta ( Figure S2). 25 These data indicate Figure 2. Phosphorylation of STE20/SPS1-related proline/ alanine-rich kinase (SPAK) and Na-K-Cl cotransporter isoform 1 (NKCC1) in aorta from wild-type (WT) and with-no-lysine kinase 3 (WNK3) knockout (KO) mice fed a normal diet or a low-salt diet.…”

mentioning

confidence: 67%

Dietary Salt Intake Regulates WNK3–SPAK–NKCC1 Phosphorylation Cascade in Mouse Aorta Through Angiotensin II

Zeniya

Sohara²,

Kita³

et al. 2013

Hypertension

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N a-K-Cl cotransporter isoform 1 (NKCC1) is involved in the regulation of vascular smooth muscle cell contractions via intracellular Cl − accumulation, membrane depolarization, and activation of voltage-gated Ca channels, leading to elevation of peripheral resistance.1 Indeed, NKCC1 knockout mice showed lower blood pressure because of decreased vascular tonus only when mice were fed a low-salt diet, as compared with those fed a normal diet, although dietary salt intake does not affect blood pressure in wild-type mice.2 This indicates that NKCC1 plays a key role in the regulation of myogenic tone in arteries by dietary salt intake.Pseudohypoaldosteronism type II is an autosomal-dominant disease characterized by salt-sensitive hypertension, hyperkalemia, and metabolic acidosis. 3 Mutations in with-no-lysine kinase 1 (WNK1) and WNK4 have been reported to cause pseudohypoaldosteronism type II. 4 It has been demonstrated previously that the WNK kinase family phosphorylated and activated oxidative stress-responsive kinase 1 (OSR1) and STE20/ SPS1-related proline/alanine-rich kinase (SPAK), and that these OSR1/SPAK kinases could phosphorylate and activate NKCC and Na-Cl cotransporter (NCC), which are solute carrier 12a (SLC12a) family cotransporters. This regulation of SLC12 family members by WNK-OSR1/SPAK signaling was confirmed in vivo in various genetically engineered mouse models. [5][6][7][8][9][10] Recently, the WNK-OSR1/SPAK-NKCC1 phosphorylation cascade in vascular smooth muscle cells was also found to be important for maintenance of vascular tone. Bergaya et al,8 as well as our group, 11 reported decreased NKCC1 phosphorylation in the aorta and decreased myogenic tone in the mesenteric arteries in WNK1 +/− mice, indicating that WNK1 plays Abstract-Na-K-Cl cotransporter isoform 1 (NKCC1) is involved in the regulation of vascular smooth muscle cell contraction. Recently, the with-no-lysine kinase (WNK)-STE20/SPS1-related proline/alanine-rich kinase (SPAK)-NKCC1 phosphorylation cascade in vascular smooth muscle cells was found to be important in the regulation of vascular tone. In this study, we investigated whether the WNK-SPAK-NKCC1 cascade in mouse aortic tissue is regulated by dietary salt intake and the mechanisms responsible. Phosphorylation of SPAK and NKCC1 was significantly reduced in the aorta in high-salt-fed mice and was increased in the aorta in low-salt-fed mice, indicating that the WNK-SPAK-NKCC1 phosphorylation cascade in the aorta was indeed regulated by dietary salt intake. Acute and chronic angiotensin II infusion increased phosphorylation of SPAK and NKCC1 in the mouse aorta. In addition, valsartan, an antagonist of angiotensin II type 1 receptor, inhibited low-salt diet-induced phosphorylation of SPAK and NKCC1, demonstrating that angiotensin II activates the WNK-SPAK-NKCC1 phosphorylation cascade through the angiotensin II type 1 receptor. However, a low-salt diet and angiotensin II together did not increase phosphorylation of SPAK and NKCC1 in the aorta in WNK3 knockout mice, indicating tha...

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confidence: 67%

Dietary Salt Intake Regulates WNK3–SPAK–NKCC1 Phosphorylation Cascade in Mouse Aorta Through Angiotensin II

Zeniya

Sohara²,

Kita³

et al. 2013

Hypertension

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“…GPCR -epidermal growth factor receptor (EGFR) cross-talk pathways are widely established and it has been reported that stimulation of angiotensin II involves transactivation of the EGFR, resulting in the activation of the MAPK pathway in various cell types (16,(41)(42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Local angiotensin II-generation in human gastric cancer: Correlation with tumor progression through the activation of ERK1/2, NF-κB and survivin

Koyama

Fushida²,

Harada³

et al. 2009

Int J Oncol

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Abstract. Angiotensin II is a main effector peptide in renin-angiotensin system, acting as a growth promoter via angiotensin II type 1 (AT1) receptor. The present study examined intrinsic angiotensin II generating system in gastric cancer and potential roles of angiotensin II in cellular proliferation and survival. The expression of AT1 receptor was examined in gastric cancer cell lines and tissues. In addition, we measured angiotensin II concentration in tissues from twenty gastric cancer and corresponding normal region using the florisil method. In vitro, we investigated the potential roles of angiotensin II in cellular proliferation and cell survival in cultured human gastric cancer cell line. The effects of AT1 receptor blocker candesartan were evaluated in a mouse model of peritoneal carcinomatosis. AT1 receptor protein was expressed in gastric cancer cell lines and tissues. Angiotensin II concentration in tumor region (1447±624 pg/g wet) was significantly higher than those of normal region (775±320 pg/g wet) (p<0.05). Angiotensin II stimulates the cell proliferation in the AT1 receptor-positive OCUM2MD3 gastric cancer cell line and this proliferative effect of angiotensin II was inhibited by a specific AT1 receptor antagonist, candesartan. We also confirmed the angiotensin II stimulated ERK1/2, nuclear transcript factor-κB (NF-κB) and surviving activation, which are central molecules of cellular proliferation and survival in OCUM2MD3 cells. Candesartan significantly prolonged survival time in a mouse model of peritoneal carcinomatosis compared with control group (p=0.0.197, log-rank test). Our data provide in vivo evidence of intrinsic angiotensin II generating system in gastric cancer and indicate locally formed angiotensin II is involved in cellular proliferation and survival.

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“…It has been recently suggested that Ras induces premature senescence in vascular cells, thereby promoting human atherosclerosis [23]. It is well recognized that Ang II mediates cell growth via a Ras-dependent mechanism [36]. It has also been reported that Aldo rapidly induces Ras protein level through a genomic mechanism, thereby promoting cell proliferation [5].…”

Section: Discussionmentioning

confidence: 99%

Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence

Min

Mogi

Iwanami

et al. 2007

Cardiovascular Research

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Objective: Our aim was to examine the possible cross-talk of angiotensin II (Ang II) and aldosterone (Aldo) in the regulation of vascular cell senescence in cultured vascular smooth muscle cells (VSMC). Methods: VSMC were prepared from thoracic aorta of adult male Sprague-Dawley rats. Cellular senescence was evaluated by senescenceassociated β-galactosidase (SA-β-gal) staining and expression of p21, p53, p16, and p27. Oxidative stress was determined by measuring NADPH oxidase activity and superoxide production. Signal transduction was examined by immunoblot analysis with or without RNA interference methods. Results: Persistent Ang II (100 nM) stimulation increased SA-β-gal-stained VSMC and enhanced expression of p21, p53, p16, p27 and Kiras2A. These effects of Ang II were markedly inhibited by treatment with a selective AT 1 receptor blocker, valsartan, but partially attenuated by a mineralocorticoid receptor antagonist, spironolactone. The culture medium of VSMC treated with Ang II (100 nM) showed a timedependent increase in Aldo concentration, which increased senescent VSMC. Antioxidant, N-acetyl-L-cysteine or superoxide dismutase attenuated Ang II-or Aldo-induced VSMC senescence and Ki-ras2A expression. A lower dose combination of Ang II (100 pM) and Aldo (1 pM) significantly enhanced SA-β-gal-stained VSMC with increases in expression of p21, p53, p16, p27 and Ki-ras2A, oxidative stress, and activity of transcription factors such as NF-κB, AP-1, whereas Ang II or Aldo alone at these doses did not affect these parameters. Kiras2A-siRNA treatment attenuated senescent VSMC, expression of p21, p53, p16 and p27, oxidative stress induced by Ang II or a lower dose combination of Ang II and Aldo. Conclusion: These results suggest that Ang II and Aldo exert cross-talk in VSMC senescence with involvement of oxidative stress and Kiras2A, and could provide a therapeutic benefit for age-related vascular disorders by blockade of both Ang II and Aldo.

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Angiotensin II-mediated vascular smooth muscle cell growth signaling

Cited by 20 publications

References 29 publications

Dietary Salt Intake Regulates WNK3–SPAK–NKCC1 Phosphorylation Cascade in Mouse Aorta Through Angiotensin II

Dietary Salt Intake Regulates WNK3–SPAK–NKCC1 Phosphorylation Cascade in Mouse Aorta Through Angiotensin II

Local angiotensin II-generation in human gastric cancer: Correlation with tumor progression through the activation of ERK1/2, NF-κB and survivin

Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence

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