Cardiac Hypertrophy in the Prague- Hypertensive Rat Is Associated with Enhanced JNK2 but not ERK Tissue Activity

Vogel, Volker; Bokemeyer, Dirk; Heller, J; Kramer, Herbert J.

doi:10.1159/000054206

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…Although there is evidence that changes in [Na + ] i and [Mg 2+ ] i are associated with altered MAP kinase activity [15,16,39], the exact molecular mechanisms underlying these processes await clarification. Activation of the other major MAP kinases, p38MAP kinase and JNK, has also been shown to be augmented in hypertension [20,42]. Our findings in the present study are in agreement with previous studies.…”

Section: Figure 4 Effects Of Quinidine and Imipramine On Map Kinase Asupporting

confidence: 94%

“…In the present study vascular and renal ERK1/2 phosphorylation was significantly augmented in Ang II-induced hypertensive rats. Hyperactivation of ERK1/2 has been implicated in cellular growth processes leading to vascular and renal hypertrophy in hypertension [19][20][21][22] …”

Section: Figure 3 Effects Of Quinidine and Imipramine On Map Kinase Amentioning

confidence: 99%

“…ERK1/2 is a major growth signalling kinase, whereas JNK and p38MAP kinase influence cell survival, apoptosis, differentiation and inflammation [17,18]. Increased activation of MAP kinases has been demonstrated in cardiac, vascular and renal tissue of hypertensive rats and appears to be important in cardiovascular remodelling, renal fibrosis and inflammation in hypertension [19][20][21][22]. Because Mg 2+ modulates activity of many enzymes, including MAP kinases, it is possible that disturbances in Mg 2+ metabolism in hypertension could contribute to altered regulation of MAP kinases and consequently to vascular and renal functional and structural changes.…”

Section: Introductionmentioning

confidence: 99%

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Up-regulation of vascular and renal mitogen-activated protein kinases in hypertensive rats is normalized by inhibitors of the Na+/Mg2+ exchanger

Touyz

Yao

2003

Clinical Science

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In the present in vivo study, we have investigated whether inhibitors of the Na(+)/Mg(2+) exchanger quinidine and imipramine influence the development of hypertension and whether this is associated with modulation of mitogen-activated protein (MAP) kinase activation in arteries and kidneys of hypertensive rats. Sprague-Dawley rats were divided into four groups (n =6/group): control (vehicle), angiotensin II (Ang II; 150 ng/kg of body weight per min subcutaneously), quinidine [Ang II (150 ng/kg of body weight per min)+quinidine (5 mg/kg of body weight per day in food)] and imipramine groups [Ang II (150 ng/kg of body weight per min)+imipramine (5 mg/kg/day in food)]. Rats were studied for 3 weeks. Phosphorylation of vascular and renal extracellular-signal-regulated protein kinase 1/2 (ERK1/2), p38MAP kinase and c-Jun N-terminal kinase (JNK) were assessed using phospho-specific antibodies. Ang II increased systolic blood pressure from 112+/-5 mmHg to 215+/-9 mmHg ( P <0.01). Development of hypertension was attenuated in Ang II-infused rats treated with quinidine (173+/-6 mmHg) and imipramine (152+/-6 mmHg) (P <0.01). Phosphorylation of ERK1/2, p38MAP kinase and JNK, which were increased 2-3-fold in arteries of the Ang II group, were reduced by quinidine and imipramine (P <0.05). Activation of renal MAP kinases was also increased in the Ang II group (P <0.05). Quinidine and imipramine reduced the phosphorylation of renal ERK1/2, but did not modify renal p38MAP kinase or JNK. Our data demonstrate that Ang II induces severe hypertension in Sprague-Dawley rats and this is associated with increased phosphorylation of vascular and renal MAP kinases. Quinidine and imipramine attenuated the development of hypertension and normalized MAP kinase activity. The findings from this study suggest a possible role for the Na(+)/Mg(2+) exchanger in vascular signalling events associated with blood pressure elevation in Ang II-dependent hypertension.

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Section: Figure 4 Effects Of Quinidine and Imipramine On Map Kinase Asupporting

confidence: 94%

Section: Figure 3 Effects Of Quinidine and Imipramine On Map Kinase Amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Up-regulation of vascular and renal mitogen-activated protein kinases in hypertensive rats is normalized by inhibitors of the Na+/Mg2+ exchanger

Touyz

Yao

2003

Clinical Science

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“…Previous studies have suggested that JNK is involved in cardiac hypertrophy in hypertensive rats [33]. In addition, we have confirmed that JNK is also involved in the upregulation of ET A receptors induced by DSP in rat basilar arteries [12].…”

Section: Discussionsupporting

confidence: 83%

DMSO-Soluble Cigarette Smoke Particles Alter the Expression of Endothelin B Receptor in Rat Coronary Artery

Huang

Zhang²,

He³

et al. 2013

J Vasc Res

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In coronary artery diseases, cigarette smoking is a risk factor and the endothelin system plays a key role in the pathogenesis. This study was to examine if dimethylsulfoxide-soluble smoke particles (DSP) upregulate endothelin type-B (ET_B) receptors in the coronary artery and investigate the mechanism. The isolated rat coronary arteries were organ-cultured for 24 h. The contractile response of the coronary artery was recorded by myograph. The mRNA and protein expression of the ET_B receptors was studied using quantitative real-time PCR and immunohistochemistry. Results showed that the ET_B receptor agonist, sarafotoxin 6c, induced a weak contraction in the fresh coronary artery. After culture, the contraction curve mediated by ET_B receptor was shifted towards the left with an increased E_max of 152 ± 12%. DSP of 0.2 and 0.4 µl/ml shifted the concentration-contractile curves towards the left with further increased E_max of 270 ± 26 and 280 ± 29%, respectively. The culture increased ET_B receptor mRNA and protein levels from fresh arteries, which was further enhanced by DSP. PD98059 (ERK1/2 inhibitor), wedelolactone (NF-κB inhibitor), actinomycin D or cycloheximide significantly inhibited the DSP-enhanced contraction and expression of mRNA and protein of the ET_B receptor. However, SB203580 (p38 inhibitor) further increased DSP-enhanced contraction and protein expression of the ET_B receptor. The results indicate that DSP upregulates ET_B receptors in rat coronary artery via ERK1/2 and the NF-κB pathway.

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“…Hypertension induces remodeling, leading to functional consequences associated with heart failure 3, 4) , which involves excess parallel signal transduction events 35,36) . Innate immunity is activated in the injured heart in different ways and is evident in the form of cytokine release from the heart and the activation of TLRs that play a role in recognizing danger as well as NF-κB, which regulates gene programs involved in inflammation 8, 11,37) .…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Ⅱ Activates MCP-1 and Induces Cardiac Hypertrophy and Dysfunction via Toll-like Receptor 4

Matsuda

Umemoto

Yoshimura

et al. 2015

J Atheroscler Thromb

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Aim Angiotensin II (AngII) produces reactive oxygen species (ROS), thus contributing to the development of cardiac hypertrophy and subsequent heart failure, and stimulates the expression of monocyte chemoattractant protein-1 (MCP-1). In addition, Toll-like receptor 4 (TLR4) is involved in the upregulation of MCP-1. In order to clarify whether TLR4 is involved in the onset of cardiac dysfunction caused by AngII stimulation, we investigated the effects of TLR4 on oxidative stress, the MCP-1 expression and cardiac dysfunction in mice with AngII-induced hypertension. Methods TLR4-deficient (Tlr4lPS-d) and wild-type (WT) mice were randomized into groups treated with AngII, norepinephrine (NE) or a subdepressor dose of the AngII receptor blocker irbesartan (IRB) and Angll for two weeks. Results AngII and NE similarly increased systolic blood pressure in all drug-treated groups compared to that observed in the control group among both WT and T1r4lps-d mice (p< 0.05). In the WT mice, AngII induced cardiac hypertrophy as well as vascular remodeling and perivascular fibrosis of the intramyocardial arteries and monocyte/macrophage infiltration in the heart (P<0.05). Furthermore, AngII treatment decreased the left ventricular diastolic function and resulted in a greater left ventricular end-systolic dimension (P<0.05) in addition to producing a five-fold increase in the NADPH oxidase activity, ROS content and MCP-1 expression (P<0.05). In contrast, the Tlr4lps-d mice showed little effects of AngII on these indices. In the WT mice, IRB treatment reversed these changes compared to that seen in the mice treated with AngII alone. NE produced little effect on any of the indices in either the WT or T1r4lps-d mice. Conclusions TLR4 may be involved in the processes underlying the increased oxidative stress, selectively activated MCP-1 expression and cardiac hypertrophy and dysfunction seen in cases of AngII-induced hypertension.

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Cardiac Hypertrophy in the Prague- Hypertensive Rat Is Associated with Enhanced JNK2 but not ERK Tissue Activity

Cited by 9 publications

References 20 publications

Up-regulation of vascular and renal mitogen-activated protein kinases in hypertensive rats is normalized by inhibitors of the Na+/Mg2+ exchanger

Up-regulation of vascular and renal mitogen-activated protein kinases in hypertensive rats is normalized by inhibitors of the Na+/Mg2+ exchanger

DMSO-Soluble Cigarette Smoke Particles Alter the Expression of Endothelin B Receptor in Rat Coronary Artery

Angiotensin Ⅱ Activates MCP-1 and Induces Cardiac Hypertrophy and Dysfunction via Toll-like Receptor 4

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