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.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*