Role of ACE/AT2R complex in the control of mesenteric resistance artery contraction induced by ACE/AT1R complex activation in response to Ang I

Su, Jun; Palen, Desiree I; Boulares, Hamid; Matrougui, Khalid

doi:10.1007/s11010-007-9686-0

Cited by 7 publications

(6 citation statements)

References 26 publications

(31 reference statements)

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“…Employing rat adrenal medulla as the positive control for AT2R antibody, we obtained a distinct band at 50~ kDa (blot 5, Figure 5). This molecular weight is consistent with Abcam datasheet (http://www.abcam.com/Angiotensin-II-Type-2-Receptor-antibody-ab78747.pdf), and published data by other groups using AT2R antibody from Cell Signaling Technology 70 or from Santa Cruz Biotechnology 71 , and our previous results by AT2R antibody from Santa Cruz Biotechnology (sc-9040) 11 , which is another rigorously validated, well-characterized AT2R antibody 72 . The AT1R has a calculated mass of 40,889 Daltons as deduced from its 359 amino acid sequence 73;74 and the molecular mass of AT2R is predicated to be 41,346 Daltons based on its 363 amino acid sequence 75;76 .…”

Section: Discussionsupporting

confidence: 90%

Ontogeny of angiotensin type 2 and type 1 receptor expression in mice

Gao

Chao

Parbhu

et al. 2012

J Renin Angiotensin Aldosterone Syst

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In the current experiment, we determined AT2R and AT1R protein expression by Western blot analysis in developing normal mice. The results indicate that, (1) in all detected brain regions and in the spinal cord, adult mice exhibited significantly higher AT2R expression and lower AT1R expression in total protein extracts compared to fetuses and neonates; (2) other major organs, including heart, lung, liver, and kidney, exhibited the same expression pattern as the brain and spinal cord; (3) reciprocal changes in AT2R and AT1R expression were found in the total protein extracts from the brainstems of mice from one day prenatal to six weeks of age. There was a negative correlation between AT2R and AT1R protein expression; (4) in both membrane and cytosolic fractions from the brainstem, adult mice exhibited higher AT2R and lower AT1R expression than did fetuses and neonates; (5) in the brainstem, there were no significant differences in AT2R and AT1R mRNA levels among fetal, neonatal, and adult mice. The above results reconfirmed our previous finding in rats that adult animals have higher AT2R and lower AT1R expression compared to fetuses and neonates. These data imply an involvement of AT1R in fetal development and of AT2R in adult function.

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Section: Discussionsupporting

confidence: 90%

Ontogeny of angiotensin type 2 and type 1 receptor expression in mice

Gao

Chao

Parbhu

et al. 2012

J Renin Angiotensin Aldosterone Syst

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show abstract

“…However, the TDA exhibited a low response to Ang II compared with the other vasoconstrictors discussed above; indeed, the maximum effect for Ang II was approximately 70% of the maximal diameter, whereas all the other vasoconstrictors induced a maximum effect between 30 and 40% of the maximal diameter. However, this observation has also been reported in several papers in the second and third order of mesenteric artery [35,42,54,67]. Altogether, these results demonstrate that the TDA exhibits similar responses to contractile agents compared to those reported in the extensively studied mesenteric arteries, which makes the TDA an adequate vascular model system for vasoreactivity studies.…”

Section: Discussionsupporting

confidence: 85%

Characterization of the Thoracodorsal Artery: Morphology and Reactivity

et al. 2012

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In this paper, we describe the histological and contractile properties of the thoracodorsal artery (TDA), which indirectly feeds the spinotrapezius muscle. Our results demonstrate that the TDA is composed of approximately one-two layers of smooth muscle cells, is highly innervated with adrenergic nerves, and develops spontaneous tone at intraluminal pressures above 80 mmHg. The reactivity of the TDA in response to various contractile agonists such as phenylephrine, noradrenaline, angiotensin II, serotonin, endothelin 1 and ATP as well as vasodilators show that the TDA exhibits a remarkably comparable reactivity to what has been observed in mesenteric arteries. We further studied the different components of the TDA response to acetylcholine and found that the TDA was sensitive to TRAM 34, a blocker of the intermediate conductance potassium channel, which is highly suggestive of an endothelium-dependent hyperpolarization. We conclude that the TDA exhibits comparable characteristics to other current vascular models, with the additional advantage of being easily manipulated for molecular and ex vivo vasoreactivity studies.

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“…In addition, it has been reported that Ang II increases vasoconstriction partially through O 2 •− -induced inactivation of vasorelaxant NO 1 , although this response depends on vascular-bed and genetic background. 25, 26 In the present study, we found that contractions to the Ang II, but not KCl, are significantly increased in mesenteric arteries of the Atox1 −/− mice compared with WT mice. This is inhibited by SOD mimetic tempol.…”

Section: Discussionsupporting

confidence: 50%

Role of Copper Transport Protein Antioxidant 1 in Angiotensin II–Induced Hypertension

et al. 2012

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Extracellular superoxide dismutase (SOD3) is a secretory copper enzyme involved in protecting angiotensin II (Ang II)-induced hypertension. We previously found that Ang II upregulates SOD3 expression and activity as a counter-regulatory mechanism; however, underlying mechanisms are unclear. Antioxidant-1 (Atox1) is shown to act as a copper-dependent transcription factor as well as copper chaperone for SOD3 in vitro, but its role in Ang II-induced hypertension in vivo is unknown. Here we show that Ang II infusion increases Atox1 expression as well as SOD3 expression and activity in aortas of wild-type mice, which are inhibited in mice lacking Atox1. Accordingly, Ang II increases vascular O2•− production, reduces endothelium-dependent vasodilation and increases vasoconstriction in mesenteric arterioles to a greater extent in Atox1−/− than in wild-type mice. This contributes to augmented hypertensive response to Ang II in Atox1−/− mice. In cultured vascular smooth muscle cells, Ang II promotes translocation of Atox1 to the nucleus, thereby increasing SOD3 transcription by binding to Atox1 responsive element in the SOD3 promoter. Furthermore, Ang II increases Atox1 binding to the copper exporter ATP7A which obtains copper from Atox1 as well as translocation of ATP7A to plasma membranes where it colocalizes with SOD3. As its consequence, Ang II decreases vascular copper levels, which is inhibited in Atox1−/− mice. In summary, Atox1 functions to prevent Ang II-induced endothelial dysfunction and hyper-contraction in resistant vessels as well as hypertension in vivo by reducing extracellular O2•− levels via increasing vascular SOD3 expression and activity.

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Role of ACE/AT2R complex in the control of mesenteric resistance artery contraction induced by ACE/AT1R complex activation in response to Ang I

Cited by 7 publications

References 26 publications

Ontogeny of angiotensin type 2 and type 1 receptor expression in mice

Ontogeny of angiotensin type 2 and type 1 receptor expression in mice

Characterization of the Thoracodorsal Artery: Morphology and Reactivity

Role of Copper Transport Protein Antioxidant 1 in Angiotensin II–Induced Hypertension

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