High vascular and airway pressures increase interstitial protein mRNA expression in isolated rat lungs

We hypothesized that wall stresses produced by high peak airway (Paw) and venous (Ppv) pressures would increase mRNA levels for structural proteins of the interstitial matrix in isolated rat lungs. Groups of lungs (n = 6) were perfused for 4 h at a peak Paw of 35 cmH2O (HiPaw), cyclical peak Ppv of 28 cmH2O (HiPv), or baseline vascular and airway pressures (LoPress). In two separate groups, comparable peak pressures increased capillary filtration coefficient fourfold in each group. Northern blots were probed for mRNA of alpha 1(I), alpha 1(III), and alpha 2(IV) procollagen chains, laminin B chain, fibronectin, and transforming growth factor-beta 1, and densities were normalized to 18S rRNA. mRNA was significantly higher in the HiPv group for type I (4.3-fold) and type III (3.8-fold) procollagen and laminin B chain (4.8-fold) and in the HiPaw group for type I (2.4-fold) and type IV (4.5-fold) procollagen and laminin B chain (2.3-fold) than in the LoPress group. Only fibronectin mRNA was significantly increased (3.9-fold) in the LoPress group relative to unperfused lungs. Estimated wall stresses were highest for alveolar septa in the HiPaw group and for capillaries in the HiPv group. The different patterns of mRNA expression are attributed to different regional stresses or extent of injury.