From Field to Lab: Asking Questions about Hypoxia Regulation of Vascular Tone in Cell Culture Systems
Seals are physiologically specialized to exploit prey resources below the ocean surface through extended breath‐hold diving. This dive response includes remarkable cardiovascular control, managed regional blood flow based on metabolic need, and an ability to sustain periods without oxygen. To identi...
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Online Access: | http://dx.doi.org/10.1096/fasebj.31.1_supplement.1075.1 |
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crwiley:10.1096/fasebj.31.1_supplement.1075.1 2024-09-15T18:40:36+00:00 From Field to Lab: Asking Questions about Hypoxia Regulation of Vascular Tone in Cell Culture Systems Hindle, Allyson Allen, Kaitlin Batten, Annabelle Wareham, Lauren Buys, Emmanuel Zapol, Warren 2017 http://dx.doi.org/10.1096/fasebj.31.1_supplement.1075.1 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor The FASEB Journal volume 31, issue S1 ISSN 0892-6638 1530-6860 journal-article 2017 crwiley https://doi.org/10.1096/fasebj.31.1_supplement.1075.1 2024-08-06T04:13:53Z Seals are physiologically specialized to exploit prey resources below the ocean surface through extended breath‐hold diving. This dive response includes remarkable cardiovascular control, managed regional blood flow based on metabolic need, and an ability to sustain periods without oxygen. To identify the molecular mechanisms that underlie the seal's natural protection of critical tissues by region‐specific control of perfusion, we investigated the nitric oxide (NO) – cyclic GMP system in the vasculature of Weddell seals. In terrestrial mammals, this pathway responds to tissue hypoxia to trigger local vasodilation. Underwater, any tissue may experience hypoxia, yet perfusion remains under tight regional control. We assayed cGMP production in response to stimulation by NO donors in vitro. In intact arteries collected from animals at necropsy, preliminary results indicate that NO‐cGMP signaling may be impaired in Weddell seals compared to terrestrial mammals, however, the system remains functional in all vascular beds examined. To complement this in vitro assessment of gene expression and enzyme activities in key pathway enzymes, we established cultured endothelial cells from placental arteries in the field. After return of cryo‐preserved primary cells to the US, they were tested for expression of cell type‐specific enzymes, then experimentally perturbed to either stimulate/repress NO‐cGMP signaling or to provide hypoxia exposure. These cell resources provide an opportunity to address mechanistic questions about free‐living animals in the lab, and their phenotype can be validated through comparisons with intact tissue samples. Because diving ability defines and limits the role of marine mammals in their ecosystem, we can apply a mechanistic understanding of the dive response to understand the ability of these species to respond to natural and anthropogenic disturbance. In future, these insights also have tremendous potential for human medicine, pointing to novel therapies for cardiovascular trauma (stroke, heart ... Article in Journal/Newspaper Weddell Seals Wiley Online Library The FASEB Journal 31 S1 |
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Wiley Online Library |
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English |
description |
Seals are physiologically specialized to exploit prey resources below the ocean surface through extended breath‐hold diving. This dive response includes remarkable cardiovascular control, managed regional blood flow based on metabolic need, and an ability to sustain periods without oxygen. To identify the molecular mechanisms that underlie the seal's natural protection of critical tissues by region‐specific control of perfusion, we investigated the nitric oxide (NO) – cyclic GMP system in the vasculature of Weddell seals. In terrestrial mammals, this pathway responds to tissue hypoxia to trigger local vasodilation. Underwater, any tissue may experience hypoxia, yet perfusion remains under tight regional control. We assayed cGMP production in response to stimulation by NO donors in vitro. In intact arteries collected from animals at necropsy, preliminary results indicate that NO‐cGMP signaling may be impaired in Weddell seals compared to terrestrial mammals, however, the system remains functional in all vascular beds examined. To complement this in vitro assessment of gene expression and enzyme activities in key pathway enzymes, we established cultured endothelial cells from placental arteries in the field. After return of cryo‐preserved primary cells to the US, they were tested for expression of cell type‐specific enzymes, then experimentally perturbed to either stimulate/repress NO‐cGMP signaling or to provide hypoxia exposure. These cell resources provide an opportunity to address mechanistic questions about free‐living animals in the lab, and their phenotype can be validated through comparisons with intact tissue samples. Because diving ability defines and limits the role of marine mammals in their ecosystem, we can apply a mechanistic understanding of the dive response to understand the ability of these species to respond to natural and anthropogenic disturbance. In future, these insights also have tremendous potential for human medicine, pointing to novel therapies for cardiovascular trauma (stroke, heart ... |
format |
Article in Journal/Newspaper |
author |
Hindle, Allyson Allen, Kaitlin Batten, Annabelle Wareham, Lauren Buys, Emmanuel Zapol, Warren |
spellingShingle |
Hindle, Allyson Allen, Kaitlin Batten, Annabelle Wareham, Lauren Buys, Emmanuel Zapol, Warren From Field to Lab: Asking Questions about Hypoxia Regulation of Vascular Tone in Cell Culture Systems |
author_facet |
Hindle, Allyson Allen, Kaitlin Batten, Annabelle Wareham, Lauren Buys, Emmanuel Zapol, Warren |
author_sort |
Hindle, Allyson |
title |
From Field to Lab: Asking Questions about Hypoxia Regulation of Vascular Tone in Cell Culture Systems |
title_short |
From Field to Lab: Asking Questions about Hypoxia Regulation of Vascular Tone in Cell Culture Systems |
title_full |
From Field to Lab: Asking Questions about Hypoxia Regulation of Vascular Tone in Cell Culture Systems |
title_fullStr |
From Field to Lab: Asking Questions about Hypoxia Regulation of Vascular Tone in Cell Culture Systems |
title_full_unstemmed |
From Field to Lab: Asking Questions about Hypoxia Regulation of Vascular Tone in Cell Culture Systems |
title_sort |
from field to lab: asking questions about hypoxia regulation of vascular tone in cell culture systems |
publisher |
Wiley |
publishDate |
2017 |
url |
http://dx.doi.org/10.1096/fasebj.31.1_supplement.1075.1 |
genre |
Weddell Seals |
genre_facet |
Weddell Seals |
op_source |
The FASEB Journal volume 31, issue S1 ISSN 0892-6638 1530-6860 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1096/fasebj.31.1_supplement.1075.1 |
container_title |
The FASEB Journal |
container_volume |
31 |
container_issue |
S1 |
_version_ |
1810485002829299712 |