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. TITLE=Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models JOURNAL=Frontiers in Physiology VOLUME=Volume 12 - 2021 YEAR=2022 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.766818 DOI=10.3389/fphys.2021.766818 ISSN=1664-042X ABSTRACT=The majority of conventional techniques utilized for investigating the pathogenesis of cardiovascular disease in preclinical animal models do not permit microlevel assessment of in situ cardiomyocyte and microvascular function. Therefore, it has been difficult to establish whether cardiac dysfunction in complex multiorgan disease states such as a heart failure with preserved ejection fraction and pulmonary hypertension have their origins in microvascular dysfunction or in the cardiomyocyte. Herein we describe our approach utilizing synchrotron radiation microangiography to first, ascertain whether the growth hormone secretagogue (GHS) hexarelin is a vasodilator in the coronary circulation of normal, anaesthetised 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 endothelium-derived hyperpolarization. Previous work indicated that chronic exogenous administration of ghrelin largely prevented the pathogenesis of pulmonary hypertension in chronic hypoxia and 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 super relaxed myosin filaments contribute to diastolic dysfunction while length-dependent activation might contribute to sustained contractility of the RV. Thus, synchrotron-based imaging approaches can reveal novel insights into cardiac and coronary function in vivo.