Reparixin, an Inhibitor of CXCR1 and CXCR2 Receptor Activation, Attenuates Blood Pressure and Hypertension-Related Mediators Expression in Spontaneously Hypertensive Rats

Kim, Hye Young; Choi, Jin Hee; Kang, Young Jin; Park, So Young; Choi, Hyoung Chul; Kim, Hee Sun

doi:10.1248/bpb.34.120

Cited by 29 publications

(22 citation statements)

References 46 publications

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“…When given intravenously to rats with hypertension, reparixin, an IL-8 receptor inhibitor, caused a reduction in blood pressure, decreased expression of CXCL-8, CCL2, 12-lipoxygenase (LO), endothelin-1 (eT)-1 and angiotensin aT1 receptor. In these rats, a higher concentration of nitric oxide was also observed [34].…”

Section: Il-8 Ip-10 and Fractalkine In Hypertensionmentioning

confidence: 64%

The Role of Chemokines in Hypertension

Martynowicz¹,

Janus²,

Nowacki³

et al. 2014

Adv Clin Exp Med

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Hypertension is a major risk factor for cardiovascular disease, which is a serious health problem in the highly industrialized countries. In more than 95% of the cases, the etiology of hypertension remains unknown. a key role in the etiology of hypertension is played by endothelial dysfunction and the inflammatory reaction in the vascular wall, in which the low molecular weight proteins -so-called chemokines -are involved. The chemokines involved in the pathogenesis of hypertension include monocyte chemoattractant protein-1, MCP-1, CCL2, interferon--inducible protein (IP-10; CXCL10), interleukin-8 (IL-8; CXCL8), RaNTeS (CCL5), fractalkine (CX3CL1) and their receptors CCR2, CCR5, CXCR1, CXCR2, CXCR3 and CX3CR1. The mechanisms involving chemokines and their receptors in the pathogenesis of hypertension are complex and not fully understood. They include the impact of the migration of macrophages and monocytes to the vascular wall, endothelial dysfunction, effects on nitric oxide and endothelin-1 and smooth muscle cell proliferation. Chemokines are also involved in the pathogenesis of complications of hypertension, such as atherosclerosis, myocardial and renal fibrosis. Hypertension is one of the most important risk factors for cardiovascular diseases. In Poland, cardiovascular diseases pose a major medical, economic and social problem. The prevalence of hypertension in Poland reaches 32% of the adult population, but only one in three Poles suffering from hypertension is aware of the disease [1]. In more than 95% of the cases, the etiology of essential hypertension remains unknown. a significant role in the pathogenesis of hypertension is played by genetic factors regulating the transport of ions and water, renal hemodynamics and the function of numerous hormones such as aldosterone, catecholamines, renin, vasopressin and endothelin-1 (eT-1). The level of blood pressure depends on the interplay of numerous systems and factors such as the renin-angiotensin-aldosterone system (RaaS), the sympathetic nervous system, natriuretic peptides and the vascular endothelium. blood pressure level is also affected by factors such as sodium intake, low physical activity, stress and obesity. In recent years, attention has been paid to the participation of inflammatory factors in the etiology of hypertension leading to endothelial dysfunction, which in turn plays a key role in the pathogenesis of hypertension. Low molecular weight proteins of the cytokine family which have the ability to stimulate and control leukocyte migration -so-called chemokines -participate in the inflammatory reaction involving the vascular wall. These proteins have the ability to bind to receptors associated with 7-transdomain G proteins; however, most chemokines bind to more than one receptor, and the receptors are capable of binding more than one * dorian Nowacki's doctoral scholarship is co-financed by the european Union as part of the european Social fund.

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Section: Il-8 Ip-10 and Fractalkine In Hypertensionmentioning

confidence: 64%

The Role of Chemokines in Hypertension

Martynowicz¹,

Janus²,

Nowacki³

et al. 2014

Adv Clin Exp Med

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“…Sua ação é mediada por receptores CXCR1 e CXCR2 acoplados a proteína G (GPCRs), que têm alta afinidade por quimiocinas glutamina-leucina-arginina positivas (Mukaida 2003, Kim et al 2011. IL-8 tem sido detectada em vários tecidos humanos acometidos por condições inflamatórias como psoríase (Giustizieri et al 2001), asma e doença pulmonar obstrutiva crônica (Woodman et al 2006), todas condições associadas com severa infiltração neutrofílica.…”

Section: Introductionunclassified

Avaliação clínica e hematológica de equinos submetidos ao modelo de laminite por oligofructose, tratados ou não com um agente antagonista de receptores CXCR1/2

et al. 2013

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Pesq. Vet. Bras. 33(8):992-998, agosto 2013 992 Avaliação clínica e hematológica de equinos submetidos ao modelo de laminite por oligofructose, tratados ou não com um agente antagonista de receptores CXCR1/2 Brazil. E-mail: faleirosufmg@gmail.com Leucocytes recruitment to tissues is an essential part of the innate immune response and an unregulated process can result in tissue damage. Thus, leucocytes infiltration has been implicated in the pathogenesis of acute laminitis. The objectives of this stud were to determine the effect of an antagonist for CXCR1/2, a chemokine receptor for neutrophils attraction on clinical signs and hematological parameters in horses given oligofructose to induce laminitis. Twelve horses were given oligofructose (10g/kg bw PO) in time 0 and divided into two groups: one treated (30mg/kg bw. ICXCR1/2 IV, times 6, 12, 18 e 24 h) and the other not treated. Cardiac and respiratory frequency, rectal temperature, mucous membrane colour, digital pulse, hoof sensitivity and Obel's grade of lameness were recorded. Values for RBC, WBC and blood glucose, BUN, creatinin, ALT, AST, alkaline phosphatase, GGT, total bilirubin and serum protein concentrations were measured on times 0, 6, 12, 18, 24, 36, 48, 60 e 72 h. All the horses given oligofructose developed signs of endotoxemia like diarrhea, fever and leukocytosis and laminitis. Also, CXCR1/2 antagonist treatment did not cause any adverse effects. However, this substance when injected intravenously (30mg/kg) 6/6 hours in 4 applications, did not ameliorate clinical and hematological signs of endotoxemia.

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“…The expression levels of AT1 R and AT2 R, including hypertensive mediators, in SHR VSMCs have been shown to be significantly higher than those in normotensive WKY VSMCs [18]. In our previous studies, the down-regulatory effect of CCL5 on the expression of Ang IIinduced hypertensive mediators has been shown to be mediated through the AT2 R pathway [26].…”

Section: Discussionmentioning

confidence: 88%

“…Expressions of Ang II-induced 12-LO and ET-1 mRNA are mediated through the AT1 R and AT2 R pathways [17,18].…”

Section: R Inhibitor In Shr Vsmcsmentioning

confidence: 99%

Sulfatase 1 mediates the inhibitory effect of angiotensin II type 2 receptor inhibitor on angiotensin II-induced hypertensive mediator expression and proliferation in vascular smooth muscle cells from spontaneously hypertensive rats

Kim

2017

Yeungnam Univ J Med

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Background: Extracellular sulfatases (Sulfs), sulfatase 1 (Sulf1) and sulfatase 2 (Sulf2), play a pivotal role in cell signaling by remodeling the 6-O-sulfation of heparan sulfate proteoglycans on the cell surface. The present study examined the effects of Sulfs on angiotensin II (Ang II)-induced hypertensive mediator expression and vascular smooth muscle cells (VSMCs) proliferation in spontaneously hypertensive rats (SHR). Methods: Ang II receptors, 12-lipoxygenase (12-LO), and endothelin-1 (ET-1) messenger RNA (mRNA) expressions in SHR VSMCs were analyzed by real-time polymerase chain reaction and Western blotting. VSMCs proliferation was determined by [ 3 H]-thymidine incorporation. Results: Basal Sulfs mRNAs expression and enzyme activity were elevated in SHR VSMCs. However, Sulfs had no effect on the basal or Ang II-induced 12-LO and ET-1 mRNA expression in SHR VSMCs. The inhibition of Ang II-induced 12-LO and ET-1 expression by blockade of the Ang II type 2 receptor (AT2 R) pathway was not observed in Sulf1 siRNA-transfected SHR VSMCs. However, Sulf2 did not affect the action of AT2 R inhibitor on Ang II-induced 12-LO and ET-1 expression in SHR VSMCs. The down-regulation of Sulf1 induced a reduction of AT2 R mRNA expression in SHR VSMCs. In addition, the inhibition of Ang II-induced VSMCs proliferation by blockade of the AT2 R pathway was mediated by Sulf1 in SHR VSMCs. Conclusion: These findings suggest that extracellular sulfatase Sulf1 plays a modulatory role in the AT2 R pathway that leads to an Ang II-induced hypertensive effects in SHR VSMCs.

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Reparixin, an Inhibitor of CXCR1 and CXCR2 Receptor Activation, Attenuates Blood Pressure and Hypertension-Related Mediators Expression in Spontaneously Hypertensive Rats

Cited by 29 publications

References 46 publications

The Role of Chemokines in Hypertension

The Role of Chemokines in Hypertension

Avaliação clínica e hematológica de equinos submetidos ao modelo de laminite por oligofructose, tratados ou não com um agente antagonista de receptores CXCR1/2

Sulfatase 1 mediates the inhibitory effect of angiotensin II type 2 receptor inhibitor on angiotensin II-induced hypertensive mediator expression and proliferation in vascular smooth muscle cells from spontaneously hypertensive rats

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