Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors

Deminice, Rafael; Hyatt, Hayden W.; Yoshihara, Toshinori; Özdemir, Merve; Nguyen, Branden L.; Levine, Stephen B.; Powers, Scott K.

doi:10.3390/cells9071688

Cited by 12 publications

(14 citation statements)

References 47 publications

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“…Recently, our group has confirmed that AT1Rs exist on the sarcolemma of skeletal muscle fibers 24 and we also discovered that activation of the AT1R is required to promote VIDD. Specifically, pharmacological blockade of the AT1R attenuated MV-induced oxidative stress, contractile dysfunction, and muscle fiber atrophy in the diaphragm 25,26 .…”

Section: Accepted Articlementioning

confidence: 64%

“…Importantly, treatment of animals with Ang1-7 has been shown to protect locomotor muscles against atrophy due to prolonged inactivity or high circulating levels of AngII. 22,23 Recently, our group has confirmed that AT1Rs exist on the sarcolemma of skeletal muscle fibers 24 and we also discovered that activation of the AT1R is required to promote VIDD. Specifically, pharmacological blockade of the AT1R attenuated MV-induced oxidative stress, contractile dysfunction, and muscle fiber atrophy in the diaphragm.…”

Section: Introductionmentioning

confidence: 77%

“… 26 Moreover, this AT1R signaling is linked to a mechanical activation of AT1Rs located on the sarcolemma of diaphragm fibers. 24 Hence, a therapeutic agent that prevents VIDD must successfully block AT1R signaling. In this regard, Ang1‐7 binding to the G protein‐coupled MasR opposes the actions of the classical RAS pathway and has been shown to protect locomotor skeletal muscles against atrophy due to prolonged disuse or high circulating levels of AngII.…”

Section: Discussionmentioning

confidence: 99%

“…evidence confirms that AT1R signaling is required for both MV-induced diaphragmatic contractile dysfunction and fiber atrophy 26 . Moreover, this AT1R signaling is linked to a mechanical activation of AT1Rs located on the sarcolemma of diaphragm fibers 24 . Hence, a therapeutic agent that prevents VIDD must successfully block AT1R signaling.…”

Section: Accepted Articlementioning

confidence: 99%

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Angiotensin 1‐7 protects against ventilator‐induced diaphragm dysfunction

Yoshihara

Deminice

Hyatt

et al. 2021

Clinical Translational Sci

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Mechanical ventilation (MV) is a life-saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately, an unintended consequence of prolonged MV is the development of inspiratory weakness due to both diaphragmatic atrophy and contractile dysfunction; this syndrome is labeled ventilator-induced diaphragm dysfunction (VIDD). VIDD is clinically important because diaphragmatic weakness is an important contributor to problems in weaning patients from MV. Investigations into the pathogenesis of VIDD reveal that oxidative stress is essential for the rapid development of VIDD as redox disturbances in diaphragm fibers promote accelerated proteolysis. Currently, no standard treatment exists to prevent VIDD and therefore, developing a strategy to avert VIDD is vital. Guided by evidence indicating that activation of the classical axis of the renin-angiotensin system (RAS) in diaphragm fibers promotes oxidative stress and VIDD, we hypothesized that activation of the non-classical RAS signaling pathway via angiotensin1-7 (Ang1-7) will protect against VIDD. Using an established animal model of prolonged MV, our results disclose that infusion of Ang1-7 protects the diaphragm against MV-induced contractile dysfunction and fiber atrophy in Accepted Article This article is protected by copyright. All rights reserved both fast and slow muscle fibers. Further, Ang1-7 shielded diaphragm fibers against MV-induced mitochondrial damage, oxidative stress, and protease activation. Collectively, these results reveal that treatment with Ang1-7 protects against VIDD, in part, due to diminishing oxidative stress and protease activation. These important findings provide robust evidence that Ang 1-7 has the therapeutic potential to protect against VIDD by preventing MV-induced contractile dysfunction and atrophy of both slow and fast muscle fibers.

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Section: Accepted Articlementioning

confidence: 64%

Section: Introductionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Accepted Articlementioning

confidence: 99%

See 2 more Smart Citations

Angiotensin 1‐7 protects against ventilator‐induced diaphragm dysfunction

Yoshihara

Deminice

Hyatt

et al. 2021

Clinical Translational Sci

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“…To eliminate the risk of contamination of other tissue types that may be abundant in RAS proteins (i.e., vascular tissue), individual muscle fibers (~3 mm in length) were isolated from bundles of costal diaphragm, soleus, and plantaris muscles as previously described by Deminice et al. 34 Briefly, bundles of muscle fibers were placed in a relax solution (in mM: 100 KCl, 20 imidazole, 4 ATP, 2 EGTA, and 7 MgCl 2 ; pH adjusted to 7.0 using KOH) on ice where ~80 individual muscle fibers were carefully isolated under a stereomicroscope and placed into Eppendorf tubes prepared for Western blot analysis.…”

Section: Methodsmentioning

confidence: 99%

Alterations in renin-angiotensin receptors are not responsible for exercise preconditioning of skeletal muscle fibers

Nguyen

Yoshihara

Deminice

et al. 2021

Sports Medicine and Health Science

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Renin angiotensin system-induced muscle wasting: putative mechanisms and implications for clinicians

Afsar,

Caliskan

et al. 2024

Mol Cell Biochem

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Renin angiotensin system (RAS) alters various mechanisms related to muscle wasting. The RAS system consists of classical and non-classical pathways, which mostly function differently. Classical RAS pathway, operates through angiotensin II (AngII) and angiotensin type 1 receptors, is associated with muscle wasting and sarcopenia. On the other hand, the non-classical RAS pathway, which operates through angiotensin 1–7 and Mas receptor, is protective against sarcopenia. The classical RAS pathway might induce muscle wasting by variety of mechanisms. AngII reduces body weight, via reduction in food intake, possibly by decreasing hypothalamic expression of orexin and neuropeptide Y, insulin like growth factor-1 (IGF-1) and mammalian target of rapamycin (mTOR), signaling, AngII increases skeletal muscle proteolysis by forkhead box transcription factors (FOXO), caspase activation and muscle RING-finger protein-1 transcription. Furthermore, AngII infusion in skeletal muscle reduces phospho-Bad (Ser136) expression and induces apoptosis through increased cytochrome c release and DNA fragmentation. Additionally, Renin angiotensin system activation through AT1R and AngII stimulates tumor necrosis factor-α, and interleukin-6 which induces muscle wasting, Last but not least classical RAS pathway, induce oxidative stress, disturb mitochondrial energy metabolism, and muscle satellite cells which all lead to muscle wasting and decrease muscle regeneration. On the contrary, the non-classical RAS pathway functions oppositely to mitigate these mechanisms and protects against muscle wasting. In this review, we summarize the mechanisms of RAS-induced muscle wasting and putative implications for clinical practice. We also emphasize the areas of uncertainties and suggest potential research areas. Graphical abstract Classical and non-classical renin angiotensin systems (RAS) play opposing roles in muscle wasting. Classical RAS system operates through Angiotensin (Ang)I/ACE/AngII)/Angiotensin Type 1 Receptor (AT1R) and induces muscle wasting by mechanisms including inducing anorexia, ubiquitin–proteasome system (UPS), apoptosis, inflammation, oxidative stress, mitochondrial dysfunction, albuminuria, fibrosis (increasing transforming growth factor beta, connective tissue growth factor) and decrease insulin-like growth factor 1 (IGF-1) signaling, vitamin D and satellite cell function. Non-classical RAS system operates through Angiotensin1/ACE2/Ang (1–7)/Mas Receptor and have opposite actions to classical RAS system and protects against muscle wasting.

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Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors

Cited by 12 publications

References 47 publications

Angiotensin 1‐7 protects against ventilator‐induced diaphragm dysfunction

Angiotensin 1‐7 protects against ventilator‐induced diaphragm dysfunction

Alterations in renin-angiotensin receptors are not responsible for exercise preconditioning of skeletal muscle fibers

Renin angiotensin system-induced muscle wasting: putative mechanisms and implications for clinicians

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