Rosuvastatin blocks allergic airway vagal hypertonia via reversed
central CD73 downregulation in rats
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.