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Rosuvastatin blocks allergic airway vagal hypertonia via reversed central CD73 downregulation in rats
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  • Hong Chen,
  • Ming Zeng,
  • Yun Lin,
  • Jialun Jiang,
  • Yi Yang,
  • Yonghua Chen,
  • Chunmei Xia,
  • Jin Wang,
  • Jijiang Wang
Hong Chen
Fudan University School of Basic Medical Sciences
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Ming Zeng
Fudan University School of Basic Medical Sciences
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Yun Lin
Fudan University School of Basic Medical Sciences
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Jialun Jiang
Fudan University School of Basic Medical Sciences
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Yi Yang
Fudan University School of Basic Medical Sciences
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Yonghua Chen
Fudan University School of Basic Medical Sciences
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Chunmei Xia
Fudan University School of Basic Medical Sciences
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Jin Wang
Fudan University School of Basic Medical Sciences
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Jijiang Wang
Fudan University School of Basic Medical Sciences
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Abstract

Background In asthma, the decrease of pulmonary function and occurrence of pulmonary inflammation are largely attributed to the increase of airway vagal activity, of which the genesis involves disrupted degradation of central extracellular ATP to adenosine due to decreased expression and activity of ecto-5’-nucleotidase (CD73). Meanwhile, the therapeutic use of statins reportedly is able to alleviate asthma; however, the mechanisms remain unclear. This study test whether rosuvastatin is able to attenuate the downregulation of central CD73 and, subsequently, attenuate the increase of airway vagal activity in the rat model of allergic asthma. Methods An experimental rat model of allergic asthma was prepared using ovalbumin. During the sensitization period, ovalbumin was inhaled alone or in combination with rosuvastatin. Plethysmographic measurement of pulmonary function was used to evaluate airway vagal activity; molecular biological assay was used to examine the expression and activity of medullary CD73 and the expression of eosinophil cationic protein 1 (ECP1) in the lungs. Results In ovalbumin-sensitized rats, the decreases in the expression and activity of medullary CD73 and the increases in the expression of ECP1 in the lungs and ATP concentration in cerebral spinal fluid were completely reversed by inhaled rosuvastatin, so was the increase of airway vagal activity manifested by the atropine-sensitive increase of airway resistance and decrease of airway compliance. Conclusions In the rat model of allergic asthma, inhaled rosuvastatin reverses the decreases in the expression and activity of brainstem CD73, which prevents pulmonary function decrease via an abolished increase of airway vagal activity.