Cargando…
Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors
Abundant evidence reveals that activation of the renin-angiotensin system promotes skeletal muscle atrophy in several conditions including congestive heart failure, chronic kidney disease, and prolonged mechanical ventilation. However, controversy exists about whether circulating angiotensin II (Ang...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407103/ https://www.ncbi.nlm.nih.gov/pubmed/32674346 http://dx.doi.org/10.3390/cells9071688 |
_version_ | 1783567548322676736 |
---|---|
author | Deminice, Rafael Hyatt, Hayden Yoshihara, Toshinori Ozdemir, Mustafa Nguyen, Branden Levine, Sanford Powers, Scott |
author_facet | Deminice, Rafael Hyatt, Hayden Yoshihara, Toshinori Ozdemir, Mustafa Nguyen, Branden Levine, Sanford Powers, Scott |
author_sort | Deminice, Rafael |
collection | PubMed |
description | Abundant evidence reveals that activation of the renin-angiotensin system promotes skeletal muscle atrophy in several conditions including congestive heart failure, chronic kidney disease, and prolonged mechanical ventilation. However, controversy exists about whether circulating angiotensin II (AngII) promotes skeletal muscle atrophy by direct or indirect effects; the centerpiece of this debate is the issue of whether skeletal muscle fibers express AngII type 1 receptors (AT1Rs). While some investigators assert that skeletal muscle expresses AT1Rs, others argue that skeletal muscle fibers do not contain AT1Rs. These discordant findings in the literature are likely the result of study design flaws and additional research using a rigorous experimental approach is required to resolve this issue. We tested the hypothesis that AT1Rs are expressed in both human and rat skeletal muscle fibers. Our premise was tested using a rigorous, multi-technique experimental design. First, we established both the location and abundance of AT1Rs on human and rat skeletal muscle fibers by means of an AngII ligand-binding assay. Second, using a new and highly selective AT1R antibody, we carried out Western blotting and determined the abundance of AT1R protein within isolated single muscle fibers from humans and rats. Finally, we confirmed the presence of AT1R mRNA in isolated single muscle fibers from rats. Our results support the hypothesis that AT1Rs are present in both human and rat skeletal muscle fibers. Moreover, our experiments provide the first evidence that AT1Rs are more abundant in fast, type II muscle fibers as compared with slow, type I fibers. Together, these discoveries provide the foundation for an improved understanding of the mechanism(s) responsible for AngII-induced skeletal muscle atrophy. |
format | Online Article Text |
id | pubmed-7407103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74071032020-08-11 Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors Deminice, Rafael Hyatt, Hayden Yoshihara, Toshinori Ozdemir, Mustafa Nguyen, Branden Levine, Sanford Powers, Scott Cells Article Abundant evidence reveals that activation of the renin-angiotensin system promotes skeletal muscle atrophy in several conditions including congestive heart failure, chronic kidney disease, and prolonged mechanical ventilation. However, controversy exists about whether circulating angiotensin II (AngII) promotes skeletal muscle atrophy by direct or indirect effects; the centerpiece of this debate is the issue of whether skeletal muscle fibers express AngII type 1 receptors (AT1Rs). While some investigators assert that skeletal muscle expresses AT1Rs, others argue that skeletal muscle fibers do not contain AT1Rs. These discordant findings in the literature are likely the result of study design flaws and additional research using a rigorous experimental approach is required to resolve this issue. We tested the hypothesis that AT1Rs are expressed in both human and rat skeletal muscle fibers. Our premise was tested using a rigorous, multi-technique experimental design. First, we established both the location and abundance of AT1Rs on human and rat skeletal muscle fibers by means of an AngII ligand-binding assay. Second, using a new and highly selective AT1R antibody, we carried out Western blotting and determined the abundance of AT1R protein within isolated single muscle fibers from humans and rats. Finally, we confirmed the presence of AT1R mRNA in isolated single muscle fibers from rats. Our results support the hypothesis that AT1Rs are present in both human and rat skeletal muscle fibers. Moreover, our experiments provide the first evidence that AT1Rs are more abundant in fast, type II muscle fibers as compared with slow, type I fibers. Together, these discoveries provide the foundation for an improved understanding of the mechanism(s) responsible for AngII-induced skeletal muscle atrophy. MDPI 2020-07-14 /pmc/articles/PMC7407103/ /pubmed/32674346 http://dx.doi.org/10.3390/cells9071688 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Deminice, Rafael Hyatt, Hayden Yoshihara, Toshinori Ozdemir, Mustafa Nguyen, Branden Levine, Sanford Powers, Scott Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors |
title | Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors |
title_full | Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors |
title_fullStr | Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors |
title_full_unstemmed | Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors |
title_short | Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors |
title_sort | human and rodent skeletal muscles express angiotensin ii type 1 receptors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407103/ https://www.ncbi.nlm.nih.gov/pubmed/32674346 http://dx.doi.org/10.3390/cells9071688 |
work_keys_str_mv | AT deminicerafael humanandrodentskeletalmusclesexpressangiotensiniitype1receptors AT hyatthayden humanandrodentskeletalmusclesexpressangiotensiniitype1receptors AT yoshiharatoshinori humanandrodentskeletalmusclesexpressangiotensiniitype1receptors AT ozdemirmustafa humanandrodentskeletalmusclesexpressangiotensiniitype1receptors AT nguyenbranden humanandrodentskeletalmusclesexpressangiotensiniitype1receptors AT levinesanford humanandrodentskeletalmusclesexpressangiotensiniitype1receptors AT powersscott humanandrodentskeletalmusclesexpressangiotensiniitype1receptors |