Katayose D, Ohe M, Yamauchi K, Ogata M, Shirato K, Fujita H, Shibahara S, Takishima T
First Department of Internal Medicine, Tohoku University School of Medicine, Miyagi, Japan.
Am J Physiol. 1993 Feb;264(2 Pt 1):L100-6. doi: 10.1152/ajplung.1993.264.2.L100.
To study the molecular basis of vascular remodeling in pulmonary hypertension, we developed an experimental system in which male Sprague-Dawley rats were exposed to hypoxia for up to 3 wk. Both the right ventricular systolic pressure and gravimetric index for right ventricular hypertrophy were higher in rats exposed to hypoxia for 3 wk than those of age-matched control rats (P < 0.01), indicating that pulmonary hypertension was established under conditions used. To examine the possible involvement of platelet-derived growth factor (PDGF) in the pulmonary vascular remodeling caused by hypoxia, we cloned rat PDGF A- and B-chain cDNA and prepared specific cRNA probes. Northern blot analysis revealed that PDGF B-chain mRNA levels in the lungs were increased, reached a maximum of day 1, and were sustained at day 3, whereas PDGF A-chain mRNA levels reached a maximum on day 3. Thus the increase in the PDGF B-chain mRNA level precedes that in the PDGF A-chain mRNA level. These results suggest that the PDGF A- and B-chain products may be coordinately and sequentially involved in hypoxic pulmonary vascular remodeling.
