Effect of MAPK inhibition on the hypoxia hypercapnia-induced pulmonary vasoconstriction

AIM: To investigate isometric force displacement in isolated rat main pulmonary artery rings and right main branch pulmonary artery (second pulmonary artery) rings during hypoxia hypercapnia and the role of mitogen activated protein kinase (MAPK). METHODS: The main pulmonary artery rings were dissected from the male Sprague-Dawley rats and were randomly divided into control group and hypoxia hypercapnia group. The second pulmonary artery rings were also randomly divided into control group, hypoxia hypercapnia group, DMSO incubation group, U0126 incubation group and SB203580 incubation group. The tension changes of pulmonary artery rings were monitored in vitro. RESULTS: Under normoxia conditions, there was no statistically significant change between main pulmonary artery rings and second pulmonary artery rings. A biphasic pulmonary artery contractile response to hypoxia hypercapnia in the second pulmonary artery rings was observed instead of a sharp and transient increase in the main pulmonary artery tension. Both p38 MAPK inhibitor SB203580 and ERK1/2 inhibitor U0126 significantly attenuated the delayed, but not early, contractile phase of the biphasic pulmonary artery contraction. CONCLUSION: Acute hypoxia hypercapnia causes a biphasic pulmonary artery contractile response in the second pulmonary artery, and p38 MAPK and ERK1/2 may be two key mediators in the process.