Effect of Rho-kinase inhibition on complexity of respiratory dynamics in asthmatic guinea pigs

Asthma represents an episodic and fluctuating behavior which is associated with decreased complexity of respiratory dynamics. There are evidences to show that asthma severity or control is associated with changes in lung function variability. Understanding the pathophysiological basis of such variable behavior may provide opportunities to develop better-targeted intervention and treatment strategies. Since biological roles associated with Rho-kinase are related to pathophysiological features of asthma, we investigated the effect of Rho-kinase inhibition on complexity of respiratory dynamics in guinea pigs modal asthma. Male Dunkin-Hartley guinea-pigs were exposed to 12 inhalations with ovalbumin or saline for 15 min, every 3 d. Animals were treated with inhaled Rho-kinase inhibitor (y-27632) or saline before each allergen challenge. We recorded respiration of conscious animals using whole-body plethysmography. Exposure to ovalbumin induced lung inflammation, airway hyperresponsiveness and remodeling, including goblet cell hyperplasia, increase in the thickness of airways smooth muscles and subepithelial collagen deposition. Entropy analysis of lung function variability showed decreased irregularity (less complexity) of respiratory rhythm in asthmatic guinea pigs. Rho-kinase inhibitor attenuated airway hyperresponsiveness and inhibited airway remodeling, but had no significant effect on lung inflammation and decreased complexity of respiratory dynamics. It seems that airway hyperresponsiveness and remodeling do not involve in complexity of respiratory dynamics. Inflammation may be the main cause of sift in the respiratory dynamics away from the normal fluctuation in asthma.