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Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models
The majority of the conventional techniques that are utilized for investigating the pathogenesis of cardiovascular disease in preclinical animal models do not permit microlevel assessment of in situ cardiomyocyte and microvascular functions. Therefore, it has been difficult to establish whether card...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814524/ https://www.ncbi.nlm.nih.gov/pubmed/35126171 http://dx.doi.org/10.3389/fphys.2021.766818 |
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author | Waddingham, Mark T. Tsuchimochi, Hirotsugu Sonobe, Takashi Asano, Ryotaro Jin, Huiling Ow, Connie P. C. Schwenke, Daryl O. Katare, Rajesh Aoyama, Kohki Umetani, Keiji Hoshino, Masato Uesugi, Kentaro Shirai, Mikiyasu Ogo, Takeshi Pearson, James T. |
author_facet | Waddingham, Mark T. Tsuchimochi, Hirotsugu Sonobe, Takashi Asano, Ryotaro Jin, Huiling Ow, Connie P. C. Schwenke, Daryl O. Katare, Rajesh Aoyama, Kohki Umetani, Keiji Hoshino, Masato Uesugi, Kentaro Shirai, Mikiyasu Ogo, Takeshi Pearson, James T. |
author_sort | Waddingham, Mark T. |
collection | PubMed |
description | The majority of the conventional techniques that are utilized for investigating the pathogenesis of cardiovascular disease in preclinical animal models do not permit microlevel assessment of in situ cardiomyocyte and microvascular functions. Therefore, it has been difficult to establish whether cardiac dysfunction in complex multiorgan disease states, such as heart failure with preserved ejection fraction and pulmonary hypertension, have their origins in microvascular dysfunction or rather in the cardiomyocyte. Herein, we describe our approach of utilizing synchrotron radiation microangiography to, first, ascertain whether the growth hormone secretagogue (GHS) hexarelin is a vasodilator in the coronary circulation of normal and anesthetized Sprague-Dawley rats, and next investigate if hexarelin is able to prevent the pathogenesis of right ventricle (RV) dysfunction in pulmonary hypertension in the sugen chronic hypoxia model rat. We show that acute hexarelin administration evokes coronary microvascular dilation through GHS-receptor 1a and nitric oxide, and through endothelium-derived hyperpolarization. Previous work indicated that chronic exogenous administration of ghrelin largely prevented the pathogenesis of pulmonary hypertension in chronic hypoxia and in monocrotaline models. Unexpectedly, chronic hexarelin administration prior to sugen chronic hypoxia did not prevent RV hypertrophy or RV cardiomyocyte relaxation impairment. Small-angle X-ray scattering revealed that super relaxed myosin filaments contributed to diastolic dysfunction, and that length-dependent activation might contribute to sustained contractility of the RV. Thus, synchrotron-based imaging approaches can reveal novel insights into cardiac and coronary functions in vivo. |
format | Online Article Text |
id | pubmed-8814524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88145242022-02-05 Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models Waddingham, Mark T. Tsuchimochi, Hirotsugu Sonobe, Takashi Asano, Ryotaro Jin, Huiling Ow, Connie P. C. Schwenke, Daryl O. Katare, Rajesh Aoyama, Kohki Umetani, Keiji Hoshino, Masato Uesugi, Kentaro Shirai, Mikiyasu Ogo, Takeshi Pearson, James T. Front Physiol Physiology The majority of the conventional techniques that are utilized for investigating the pathogenesis of cardiovascular disease in preclinical animal models do not permit microlevel assessment of in situ cardiomyocyte and microvascular functions. Therefore, it has been difficult to establish whether cardiac dysfunction in complex multiorgan disease states, such as heart failure with preserved ejection fraction and pulmonary hypertension, have their origins in microvascular dysfunction or rather in the cardiomyocyte. Herein, we describe our approach of utilizing synchrotron radiation microangiography to, first, ascertain whether the growth hormone secretagogue (GHS) hexarelin is a vasodilator in the coronary circulation of normal and anesthetized Sprague-Dawley rats, and next investigate if hexarelin is able to prevent the pathogenesis of right ventricle (RV) dysfunction in pulmonary hypertension in the sugen chronic hypoxia model rat. We show that acute hexarelin administration evokes coronary microvascular dilation through GHS-receptor 1a and nitric oxide, and through endothelium-derived hyperpolarization. Previous work indicated that chronic exogenous administration of ghrelin largely prevented the pathogenesis of pulmonary hypertension in chronic hypoxia and in monocrotaline models. Unexpectedly, chronic hexarelin administration prior to sugen chronic hypoxia did not prevent RV hypertrophy or RV cardiomyocyte relaxation impairment. Small-angle X-ray scattering revealed that super relaxed myosin filaments contributed to diastolic dysfunction, and that length-dependent activation might contribute to sustained contractility of the RV. Thus, synchrotron-based imaging approaches can reveal novel insights into cardiac and coronary functions in vivo. Frontiers Media S.A. 2022-01-21 /pmc/articles/PMC8814524/ /pubmed/35126171 http://dx.doi.org/10.3389/fphys.2021.766818 Text en Copyright © 2022 Waddingham, Tsuchimochi, Sonobe, Asano, Jin, Ow, Schwenke, Katare, Aoyama, Umetani, Hoshino, Uesugi, Shirai, Ogo and Pearson. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Waddingham, Mark T. Tsuchimochi, Hirotsugu Sonobe, Takashi Asano, Ryotaro Jin, Huiling Ow, Connie P. C. Schwenke, Daryl O. Katare, Rajesh Aoyama, Kohki Umetani, Keiji Hoshino, Masato Uesugi, Kentaro Shirai, Mikiyasu Ogo, Takeshi Pearson, James T. Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models |
title | Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models |
title_full | Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models |
title_fullStr | Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models |
title_full_unstemmed | Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models |
title_short | Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models |
title_sort | using synchrotron radiation imaging techniques to elucidate the actions of hexarelin in the heart of small animal models |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814524/ https://www.ncbi.nlm.nih.gov/pubmed/35126171 http://dx.doi.org/10.3389/fphys.2021.766818 |
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