Adventitial growth and lung connective tissue growth factor expression in pulmonary arterioles due to hypobaric...

Forty broilers maintained under natural hypobaric hypoxia (2,638 m above sea level) and 20 maintained under relative normoxia (460 m above sea level) were selected as pulmonary hypertensive (PHB) and nonpulmonary hypertensive (NPHB), to estimate the degree of the adventitial vascular thickness in lung arterioles and connective tissue growth factor (CTGF) expression in lung. In each group, the adventitial thickness (%AT) of 20 arterioles with 100 to 250 μm of external diameter was measured in lung samples of 24 and 42-day-old broilers. Also, mRNA extraction and real-time reverse transcription-PCR analysis were used to measure lung CTGF expression. The %AT was higher in PHB at 42 D as compared to NPHB at both ages and PHB at 24 D; however, the same differences were not evidenced at 24 D. In the 2 ages evaluated, differences were observed in the %AT between broilers under hypobaric hypoxia (PHB and NPHB) and under relative normoxia (P < 0.01). In broilers subjected to relative normoxia, no significant differences were found at any of the 2 ages. The expression levels of CTGF mRNA were higher in PHB compared to NPHB at the 2 ages. The %AT was higher in PHB with high levels of expression of CTGF mRNA than those NPHB with low expression of CTGF mRNA. This study showed that adventitial thickening is part of the pulmonary hypertension (PH) physiopathology in broilers exposed to hypobaric hypoxia, in which CTGF appears to be a fibrosis enhancer. Although present data suggest that adventitial engrossment could be a time-dependent process, individual susceptibility and the variable time-course of PH pathophysiology have to be considered.