摘要
Abstract Objective To investigate the effects of endothelin on the mechanism of exercise induced asthma by taking an animal experiment with Bosentan. Methods Nineteen pathogen free Hartley Guinea pigs were divided into 2 groups. A) Bosentan group (n=10): Bosentan group (Hoffmann La Roche) was administered by intraperitoneal injection 24, 16, 8h prior to isocapnic hyperpnea challenge in each dose of 30 mg/kg body weight. B) Control group (n=9): the control group was given water for injection at same interval time by i.p. (0.5 ml/animal). Lung resistance (R L) and dynamic compliance (Cdyn) of 2 groups were measured before isocapnic hyperpnea challenge as baseline value. After the measurement of baseline value, the tracheal cannula was connected to a rodent respirator(Jiang Nan Ⅰ, Chinese 2nd Military Medical University) to provide mechanical ventilation (8 ml/animal, 100 breaths/min) for 5 minutes. The ventilator was connected to a compressed gas bag contained with dry 5%CO 2-95%O 2 mixture. After isocapnic hyperpnea challenge R L and Cdyn were measured again immediately, then, the airway lumens of guinea Pulmonary Department, Zhongshan Hospital, Shanghai Medical University, Shanghai 200032, China (Liang YJ and Cai YY) pigs were washed with two aliquots (5 ml) of normal saline. The collected volume of BALF from both groups was recorded. Results In control group, isocapnic hyperpnea elicited a marked increase in R L and decrease in Cdyn, which usually began just finish of the hyperpnea challenge and showed a peak at 5 min. There was a 3.82 fold increase in R L and 49.9% decrease in Cdyn during peak bronchoconstriction. In contrast, R L and Cdyn of the Guinea pigs from Bosentan group did not change significantly. The collected volume of BALF of Bosentan group (58.8%±6.1%) was more than that of control group (42.3%±5.5%) (P<0.001). The correlation between the collected volume of BALF and the R L showed statistical significance (P<0.05). Conclusions The endothelin (ET) receptor antagonist (Bosentan) inhibited the bronchoconstriction induced by isocapnic hyperpnea in Guinea pigs. Our data demonstrated that ET may participate the mechanism of exercise induced asthma. Bosentan might be a potentially useful drug in the management of clinical disorders associated with bronchoconstriction.
Abstract Objective To investigate the effects of endothelin on the mechanism of exercise induced asthma by taking an animal experiment with Bosentan. Methods Nineteen pathogen free Hartley Guinea pigs were divided into 2 groups. A) Bosentan group (n=10): Bosentan group (Hoffmann La Roche) was administered by intraperitoneal injection 24, 16, 8h prior to isocapnic hyperpnea challenge in each dose of 30 mg/kg body weight. B) Control group (n=9): the control group was given water for injection at same interval time by i.p. (0.5 ml/animal). Lung resistance (R L) and dynamic compliance (Cdyn) of 2 groups were measured before isocapnic hyperpnea challenge as baseline value. After the measurement of baseline value, the tracheal cannula was connected to a rodent respirator(Jiang Nan Ⅰ, Chinese 2nd Military Medical University) to provide mechanical ventilation (8 ml/animal, 100 breaths/min) for 5 minutes. The ventilator was connected to a compressed gas bag contained with dry 5%CO 2-95%O 2 mixture. After isocapnic hyperpnea challenge R L and Cdyn were measured again immediately, then, the airway lumens of guinea Pulmonary Department, Zhongshan Hospital, Shanghai Medical University, Shanghai 200032, China (Liang YJ and Cai YY) pigs were washed with two aliquots (5 ml) of normal saline. The collected volume of BALF from both groups was recorded. Results In control group, isocapnic hyperpnea elicited a marked increase in R L and decrease in Cdyn, which usually began just finish of the hyperpnea challenge and showed a peak at 5 min. There was a 3.82 fold increase in R L and 49.9% decrease in Cdyn during peak bronchoconstriction. In contrast, R L and Cdyn of the Guinea pigs from Bosentan group did not change significantly. The collected volume of BALF of Bosentan group (58.8%±6.1%) was more than that of control group (42.3%±5.5%) (P<0.001). The correlation between the collected volume of BALF and the R L showed statistical significance (P<0.05). Conclusions The endothelin (ET) receptor antagonist (Bosentan) inhibited the bronchoconstriction induced by isocapnic hyperpnea in Guinea pigs. Our data demonstrated that ET may participate the mechanism of exercise induced asthma. Bosentan might be a potentially useful drug in the management of clinical disorders associated with bronchoconstriction.
