Expression of myosin heavy-chain isoforms in the respiratory muscles following inspiratory resistive breathing

We investigated the effect of inspiratory resistive breathing (IRB) on the expression of the genes encoding fast and slow isoforms of myosin heavy cha in (MyHC) in respiratory muscles. Eleven mongrel dogs were studied for base line MyHC messenger RNA (mRNA) expression, seven of which were also used to study the effects of IRB. For this latter objective, awake and spontaneous ly breathing animals were subjected to 2 h of IRB (80 cm H2O/L/s) per day f or four consecutive days, mRNA expression was assessed in the diaphragm, ex ternal intercostal muscle, and a limb muscle, using both slot-blot and in s itu hybridizations with isoform-specific probes, A current semiquantitative scoring method (from 0 to 4) was used to quantify the in situ mRNA express ion levels, and slot-blot data were analyzed with densitometry. Prior to IR B, slow- and fast-MyHC mRNA expression was moderate, similar, and homogeneo us throughout the different regions of the diaphragm, with scores of 1.50 /- 0.54 (mean +/- SD) for slow and 2.13 +/- 0.35 for fast mRNAs in the cost al region of the diaphragm, and of 1.81 +/- 0.37 for slow and 2.13 +/- 0.64 for fast mRNAs in the crural region of the diaphragm. Although expression of fast-MyHC mRNA remained unchanged after IRB, the relative expression of the mRNA for the slow isoform increased in costal (+30%), crural (+12%), an d external intercostal (+27%) muscles. MyHC mRNA expression did not change in limb muscles. We conclude that breathing with a moderate inspiratory res istance for a short period induces the expression of slow MyHC in respirato ry muscles.