Differential vasoconstrictions induced by angiotensin II: role of AT1 and AT2 receptors in isolated C57BL/6J mouse blood vessels

Zhou, Yingbi; Dirksen, Wessel P.; Babu, Gopal J.; Periasamy, Muthu

doi:10.1152/ajpheart.00466.2003

Cited by 59 publications

(79 citation statements)

References 26 publications

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“…Because blood vessels are an important site of production/actions of both Ang II and Ang-(1-7), 5 we examined the effect of Ang-(1-7) on the phenylephrineinduced contraction of abdominal aorta, demonstrating higher AT1-R responses, 25 in wild-type or AT1-R knockout mice. Abdominal aorta from AT1-R knockout mice did not exhibit alteration in gene expression of the two other Ang- (1-7) receptors, Mas-R or AT2-R ( Figure S11).…”

Section: Ang-(1-7) Attenuates Phenylephrine-induced Contraction Of Abmentioning

confidence: 99%

Cardioprotective Angiotensin-(1–7) Peptide Acts as a Natural-Biased Ligand at the Angiotensin II Type 1 Receptor

et al. 2016

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Hyperactivity of the renin–angiotensin–aldosterone system through the angiotensin II (Ang II)/Ang II type 1 receptor (AT1-R) axis constitutes a hallmark of hypertension. Recent findings indicate that only a subset of AT1-R signaling pathways is cardiodeleterious, and their selective inhibition by biased ligands promotes therapeutic benefit. To date, only synthetic biased ligands have been described, and whether natural renin–angiotensin–aldosterone system peptides exhibit functional selectivity at AT1-R remains unknown. In this study, we systematically determined efficacy and potency of Ang II, Ang III, Ang IV, and Ang-(1–7) in AT1-R–expressing HEK293T cells on the activation of cardiodeleterious G-proteins and cardioprotective β-arrestin2. Ang III and Ang IV fully activate similar G-proteins than Ang II, the prototypical AT1-R agonist, despite weaker potency of Ang IV. Interestingly, Ang-(1–7) that binds AT1-R fails to promote G-protein activation but behaves as a competitive antagonist for Ang II/Gi and Ang II/Gq pathways. Conversely, all renin–angiotensin–aldosterone system peptides act as agonists on the AT1-R/β-arrestin2 axis but display biased activities relative to Ang II as indicated by their differences in potency and AT1-R/β-arrestin2 intracellular routing. Importantly, we reveal Ang-(1–7) a known Mas receptor-specific ligand, as an AT1-R–biased agonist, selectively promoting β-arrestin activation while blocking the detrimental Ang II/AT1-R/Gq axis. This original pharmacological profile of Ang-(1–7) at AT1-R, similar to that of synthetic AT1-R–biased agonists, could, in part, contribute to its cardiovascular benefits. Accordingly, in vivo, Ang-(1–7) counteracts the phenylephrine-induced aorta contraction, which was blunted in AT1-R knockout mice. Collectively, these data suggest that Ang-(1–7) natural-biased agonism at AT1-R could fine-tune the physiology of the renin–angiotensin–aldosterone system.

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Section: Ang-(1-7) Attenuates Phenylephrine-induced Contraction Of Abmentioning

confidence: 99%

Cardioprotective Angiotensin-(1–7) Peptide Acts as a Natural-Biased Ligand at the Angiotensin II Type 1 Receptor

et al. 2016

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“…The generation of SM2 +/-mice was previously described (Chi et al, 2008 (Zhou et al, 2003;Martin et al, 2007). Functional studies were carried out using muscle strips.…”

Section: Animals and Tissue Preparationmentioning

confidence: 99%

“…Functional studies were carried out using muscle strips. Muscles from the front wall were cut transversely into 1 mm wide and 2 mm long strips, which were further tied with thread filaments to form loops at both ends separated by a distance of 1 mm (Zhou et al, 2003).…”

Section: Animals and Tissue Preparationmentioning

confidence: 99%

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SM2+/- male mice are predisposed to develop urinary tract obstruction and hyper contractility of the bladder smooth muscle upon ageing

Chi

Zhou

Sopariwala

et al. 2011

J. Smooth Muscle Res.

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We previously showed that complete loss of smooth muscle myosin heavy chain isoform 2 (SM2) resulted in postnatal lethality, but in het mice a partial loss of SM2 (SM2 +/-) was accompanied by down-regulation of SM1 with unaltered SM2:SM1 ratio. To determine whether a normal bladder function would be maintained throughout its lifespan, we aged WT and SM2 +/-mice up to 18 months and analyzed a) SM2:SM1 ratio b) bladder smooth muscle structure and c) function in SM2 +/-het mice. A notable finding was that ~50% of 15-18 months old male SM2 +/-mice exhibited urinary retention in bladder with the distention of upper urethra. In SM2 +/-mouse bladder with urinary retention, the SM2:SM1 ratio was decreased but not in SM2 +/-mouse bladder that did not develop urinary retention. Interestingly in the distended bladder the expression levels of -actin and tropomyosin remained unaltered despite a reduction in the number of myosin thick filaments. These distended bladders showed hypersensitivity to submaximal K + depolarization and M3-receptor stimulation, without a significant increase in myosin light chain phosphorylation. We therefore suggest that a partial loss of SM2 may predispose male mice to develop lower urinary tract obstruction during ageing. In addition our data suggest that bladder obstruction can cause a further reduction in SM2 expression and SM2:SM1 ratio, and a hyper-contractility of the bladder smooth muscle.

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“…Although previous studies (38,39) have suggested that the mouse aorta has low levels of AT 1 receptors under normal conditions, others have shown that AT 1A receptors play a predominant role in angiotensin II-induced superoxide production in the mouse aorta (27). Other studies have shown that LPS upregulates AT 1 receptors (2, 37) in endothelial cells in vitro.…”

Section: Discussionmentioning

confidence: 96%

Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice

Lund¹,

Brooks²,

Faraci³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Lund DD, Brooks RM, Faraci FM, Heistad DD. Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice. Am J Physiol Heart Circ Physiol 293: H3726-H3731, 2007. First published October 26, 2007; doi:10.1152/ajpheart.01116.2007] increases levels of superoxide in blood vessels and impairs vasomotor function. Angiotensin II plays an important role in the generation of superoxide in several disease states, including hypertension and heart failure. The goal of this study was to determine whether the activation of the renin-angiotensin system contributes to oxidative stress and endothelial dysfunction after endotoxin. We examined the effects of enalapril (an angiotensinconverting enzyme inhibitor) or L-158809 (an angiotensin receptor blocker) on increases of superoxide and vasomotor dysfunction in mice treated with LPS. C57BL/6 mice were treated with either enalapril (60 mg ⅐ kg) for 4 days. After the third day, LPS (10 -20 mg/kg) or vehicle was injected intraperitoneally, and one day later, vasomotor function of the aorta was examined in vitro. After precontraction with PGF2␣, the maximal responses to sodium nitroprusside were similar in the aorta from normal and LPS-treated mice. In contrast, the relaxation to acetylcholine was impaired after LPS (54 Ϯ 5% at 10 Ϫ5 , mean Ϯ SE) compared with vessels treated with vehicle (88 Ϯ 1%; P Ͻ 0.05). Enalapril improved (P Ͻ 0.05) relaxation in response to acetylcholine to 81 Ϯ 6% after LPS. L-158809 also improved relaxation in response to acetylcholine to 77 Ϯ 4% after LPS. Superoxide (measured with lucigenin and hydroethidine) was increased (P Ͻ 0.05) in aorta after LPS, and levels were reduced (P Ͻ 0.05) following enalapril and L-158809. Thus, after LPS, enalapril and L-158809 reduce superoxide levels and improve relaxation to acetylcholine in the aorta. The findings suggest that activation of the renin-angiotensin system contributes importantly to oxidative stress and endothelial dysfunction after endotoxin. (12,13,20). Mechanisms that account for the generation of superoxide after LPS, however, are not entirely clear.Angiotensin II appears to play a key role in the generation of superoxide in several disease states, including hypertension and heart failure (9, 10, 21, 30). The activation of NADPH oxidase appears to contribute importantly to increases in the generation of superoxide by angiotensin II (3,11,28,36).Recent evidence suggests that angiotensin II may contribute to vascular dysfunction after LPS (33). This hypothesis is supported by the finding that an angiotensin-converting enzyme (ACE) inhibitor attenuated endothelial dysfunction in the aortas of rabbits 5 days after LPS. The first goal of the present study was to determine whether an ACE inhibitor, enalapril, prevents endothelial dysfunction Ͻ1 day after LPS. Because LPS causes mice to reduce food and water intake, we sought to reduce the indirect effects on blood vessels by studying vasomotor responses much sooner after LPS than in a previous study (33).Enalapril also inhibits brady...

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Differential vasoconstrictions induced by angiotensin II: role of AT1 and AT2 receptors in isolated C57BL/6J mouse blood vessels

Cited by 59 publications

References 26 publications

Cardioprotective Angiotensin-(1–7) Peptide Acts as a Natural-Biased Ligand at the Angiotensin II Type 1 Receptor

Cardioprotective Angiotensin-(1–7) Peptide Acts as a Natural-Biased Ligand at the Angiotensin II Type 1 Receptor

SM2+/- male mice are predisposed to develop urinary tract obstruction and hyper contractility of the bladder smooth muscle upon ageing

Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice

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