Exogenous ghrelin improves blood flow distribution in pulmonary hypertension—assessed using synchrotron radiation microangiography

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• 作者：Daryl O. Schwenke (1)
  Emily A. Gray (1)
  James T. Pearson (2) (3)
  Takashi Sonobe (4)
  Hatsue Ishibashi-Ueda (5)
  Isabel Campillo (1)
  Kenji Kangawa (6)
  Keiji Umetani (7)
  Mikiyasu Shirai (4)
  
• 关键词：Ghrelin ; Chronic hypoxia ; Pulmonary hypertension ; Endothelin ; 1 ; Rat
• 刊名：Pfl眉gers Archiv - European Journal of Physiology
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：462
• 期：3
• 页码：397-406
• 全文大小：499KB
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• 作者单位：Daryl O. Schwenke (1)
  Emily A. Gray (1)
  James T. Pearson (2) (3)
  Takashi Sonobe (4)
  Hatsue Ishibashi-Ueda (5)
  Isabel Campillo (1)
  Kenji Kangawa (6)
  Keiji Umetani (7)
  Mikiyasu Shirai (4)
  
  1. Department of Physiology, University of Otago, PO Box 56, Dunedin, New Zealand
  2. Department of Physiology, Monash University, Melbourne, Australia
  3. Australian Synchrotron, Melbourne, Australia
  4. Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan
  5. Department of Pathology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan
  6. National Cardiovascular Center Research Institute, Suita, Osaka, Japan
  7. Japan Synchrotron Radiation Research Institute, Sayo-gun, Hyogo, Japan
  
• ISSN：1432-2013

文摘

Ghrelin has cardioprotective properties and, recently, has been shown to improve endothelial function and reduce endothelin-1 (ET-1)-mediated vasoconstriction in peripheral vascular disease. Recently, we reported that ghrelin attenuates pulmonary hypertension (PH) caused by chronic hypoxia (CH), which we hypothesized in this study may be via suppression of the ET-1 pathway. We also aimed to determine whether ghrelin’s ability to prevent alterations of the ET-1 pathway also prevented adverse changes in pulmonary blood flow distribution associated with PH. Sprague–Dawley rats were exposed to CH (10% O2 for 2?weeks) with daily subcutaneous injections of ghrelin (150?μg/kg) or saline. Utilizing synchrotron radiation microangiography, we assessed pulmonary vessel branching structure, which is indicative of blood flow distribution, and dynamic changes in vascular responsiveness to (1) ET-1 (1?nmol/kg), (2) the ET-1A receptor antagonist, BQ-123 (1?mg/kg), and (3) ACh (3.0?μg?kg??min?). CH impaired blood flow distribution throughout the lung. However, this vessel “rarefaction-was attenuated in ghrelin-treated CH-rats. Moreover, ghrelin (1) reduced the magnitude of endothelial dysfunction, (2) prevented an increase in ET-1-mediated vasoconstriction, and (3) reduced pulmonary vascular remodeling and right ventricular hypertrophy—all adverse consequences associated with CH. These results highlight the beneficial effects of ghrelin for maintaining optimal lung perfusion in the face of a hypoxic insult. Further research is now required to establish whether ghrelin is also an effective therapy for restoring normal pulmonary hemodynamics in patients that already have established PH.