Increased perfusion pressure enhances the expression of endothelin (ETB) and angiotensin II (AT1, AT2) receptors in rat mesenteric artery smooth muscle cells

Lindstedt, Isak; Xu, Cang‐Bao; Zhang, Yaping; Edvinsson, Lars

doi:10.1080/08037050902850184

Cited by 9 publications

(10 citation statements)

References 25 publications

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“…We hypothesize that the change in vascular wall shear stress and luminal pressure that occur during a stroke or organ culture is one important factor (Olesen et al, 1988). An early study of isolated mesenteric arteries were perfused at different flow levels and perfusion pressures (Szok et al, 2001) showed that perfusion at increased pressure (150 mm Hg) results in enhanced ET B receptor mRNA expression (Lindstedt et al, 2009). This study supports the hypothesis that pressure changes can induce receptor changes.…”

Section: Upstream Initiators Of Cerebrovascular Signal Transduction Amentioning

confidence: 99%

“…In addition, ET B receptors are elevated in vascular smooth muscle following experimental chronic increases in intraluminal pressure (Lindstedt et al, 2009) and in human hypertension (Nilsson et al, 2008), which is a well-known risk factor for stroke. Thus, a range of stroke risk factors are able to enhance cerebrovascular vasoconstrictor receptor upregulation, and this mechanism may be a target for therapy to minimize stroke risk in certain patients.…”

Section: Upstream Initiators Of Cerebrovascular Signal Transduction Amentioning

confidence: 99%

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Vascular plasticity in cerebrovascular disorders

Edvinsson

Povlsen

2011

J Cereb Blood Flow Metab

115

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Cerebral ischemia remains a major cause of morbidity and mortality with little advancement in subacute treatment options. This review aims to cover and discuss novel insight obtained during the last decade into plastic changes in the vasoconstrictor receptor profiles of cerebral arteries and microvessels that takes place after different types of stroke. Receptors like the endothelin type B, angiotensin type 1, and 5-hydroxytryptamine type 1B/1D receptors are upregulated in the smooth muscle layer of cerebral arteries after different types of ischemic stroke as well as after subarachnoid hemorrhage, yielding rather dramatic changes in the contractility of the vessels. Some of the signal transduction processes mediating this receptor upregulation have been elucidated. In particular the extracellular regulated kinase 1/2 pathway, which is activated early in the process, has proven to be a promising therapeutic target for prevention of vasoconstrictor receptor upregulation after stroke. Together, those findings provide new perspectives on the pathophysiology of ischemic stroke and point toward a novel way of reducing vasoconstriction, neuronal cell death, and thus neurologic deficits after stroke.

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Section: Upstream Initiators Of Cerebrovascular Signal Transduction Amentioning

confidence: 99%

Section: Upstream Initiators Of Cerebrovascular Signal Transduction Amentioning

confidence: 99%

Vascular plasticity in cerebrovascular disorders

Edvinsson

Povlsen

2011

J Cereb Blood Flow Metab

115

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“…Studies showing increased expression of and vasoconstriction by ET B and AT 1 receptors in arteries following elevated perfusion pressure could point to the latter. Thus, using pressure myography, rabbit carotid and rat mesenteric arteries subjected to high pressure of 160 mm Hg for 6 and 17 h, respectively, showed increased levels of both mRNA and protein for the ET B receptor, compared to normotensive controls at 80-90 mm Hg [17,18]. Elevated pressure also increased AT 1 receptor protein expression in the mesenteric arteries [18].…”

Section: Discussionmentioning

confidence: 99%

“…All experimental models employed to investigate this particular phenomenon to date have included an element of reperfusion. It could be speculated that reperfusion-induced hyperperfusion could be the possible culprit as studies have shown increased ET B receptor-mediated contractile responses and receptor protein expression as well as elevated levels of AT 1 receptor mRNA in response to increased perfusion pressure [17,18,19]. On the other hand, there are also indications of a favouring of ET B receptor-mediated contractions in low-pressure systems such as veins [20,21,22].…”

Section: Introductionmentioning

confidence: 99%

Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ETB, 5-HT1B and AT1 Receptor-Mediated Contractility Downstream of Occlusion

Rasmussen

Hornbak²,

Larsen³

et al. 2013

J Vasc Res

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Background/Aims: In response to experimental stroke, a characteristic functional and expressional upregulation of contractile G-protein-coupled receptors has been uncovered in the affected cerebral vasculature; however, the mechanism initiating this phenomenon remains unknown. Methods: Using a model of permanent distal occlusion of rat middle cerebral arteries, we investigated whether there was a regional difference in receptor-mediated contractility of segments located upstream and downstream of the occlusion site. The contractile response to endothelin, angiotensin and 5-hydroxytryptamine receptor stimulation was studied by sensitive wire myograph. Results: Only downstream segments exhibited an augmented contractile response to stimulation with each of the three ligands, with the response towards sarafotoxin 6c being especially augmented compared to sham, upstream and contralateral controls. This functional increase did not seem to relate to ischemic tissue damage, inflammatory cell infiltration or the element of reperfusion. Interestingly, immunohistochemistry did not show any difference in the level of immunoreactivity towards endothelin B (ET_B) receptors between groups. Conclusion: Single artery occlusion without significant visible infarct resulted in locally increased ET_B, angiotensin type 1 and 5-hydroxytryptamine 1B receptor-mediated contractile responses only in segments located downstream of the occlusion site. This suggests lack of wall stress as an initiating trigger leading to regulation of contractile response after cerebral stroke.

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“…This is further supported by the fact that activation of the AHR by exogenous ligands sensitizes mice to Ang II-mediated hypertension [36], and induces AT1R mRNA expression in mesenteric arteries (unpublished data). Further, physiological shear stress has been shown to activate the AHR [37–39], and to increase AT1R expression [40], providing indirect evidence that AHR may contribute to the regulation of AT1R expression. Additionally, the AHR interacts with several other transcription factors including E2F1, TFIIE, TFIIB, as well as coactivators like CREB-binding protein, CBP/p300 and nuclear receptor-interacting protein 1 (RIP140) [41, 42] and thus alteration in AT1R expression could result from crosstalk with other signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness

Agbor

Elased

Walker

2011

Biochemical Pharmacology

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Hypotension in aryl hydrocarbon receptor knockout mice (ahr−/−) is mediated, in part, by a reduced contribution of angiotensin (Ang) II to basal blood pressure (BP). Since AHR is highly expressed in endothelial cells (EC), we hypothesized that EC-specific ahr−/− (ECahr−/−) mice would exhibit a similar phenotype. We generated ECahr−/− mice by crossing AHR floxed mice (ahrfx/fx) to mice expressing Cre recombinase driven by an EC-specific promoter. BP was assessed by radiotelemetry prior to and following an acute injection of Ang II or chronic treatment with an angiotensin converting enzyme inhibitor (ACEi). ECahr−/− mice were hypotensive (ECahr+/+: 116.1 ± 1.4; ECahr−/−: 107.4 ± 2.0 mmHg, n=11, p<0.05) and exhibited significantly different responses to Ang II and ACEi. While Ang II increased BP in both genotypes, the increase was sustained in ECahr+/+, whereas the increase in ECahr−/− mice steadily declined. Area under the curve analysis showed that Ang II-induced increase in diastolic BP (DBP) over 30 min was significantly lower in ECahr−/− mice (ECahr+/+ 1297 ± 223 mmHg/30 min; ECahr−/−AUC: 504 ± 138 mmHg/30 min, p<0.05). In contrast, while ACEi decreased BP in both genotypes, the subsequent rise in DBP after treatment was significantly delayed in the ECahr−/− mice. ECahr−/− mice also exhibited reduced vascular and adipose Ang II type 1 receptor (AT1R) expression, and reduced aortic Ang II-dependent vasoconstriction in the presence of vascular adipose. Taken together these data suggest that hypotension in ECahr−/− mice results from reduced vascular responsiveness to Ang II that is influenced by AT1R expression and adipose.

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Increased perfusion pressure enhances the expression of endothelin (ET_B) and angiotensin II (AT₁, AT₂) receptors in rat mesenteric artery smooth muscle cells

Cited by 9 publications

References 25 publications

Vascular plasticity in cerebrovascular disorders

Vascular plasticity in cerebrovascular disorders

Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ET<sub>B</sub>, 5-HT<sub>1B</sub> and AT<sub>1</sub> Receptor-Mediated Contractility Downstream of Occlusion

Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness

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