Two heavy chains of smooth muscle myosin (MHC1 and MHC2) were identified in pig airways and parenchyma. The ratio of MHC1 to MHC2 was the same along the bronchial tree in animals of the same age, but it changed with age (mature, young, suckling, and fetus), ranging from 0.8 in the mature to 2.2 in the fetus. Stress developed in airway (trachea, bronchus, and bronchiole) and parenchymal preparations in response to carbachol and histamine (mN/mm2) was normalized for myosin content (N/mm2 myosin). Airways from sucklings always developed the greatest stress to carbachol and histamine with the rank order of maximum force (Emax) suckling greater than fetus greater than young greater than mature for carbachol in large airways. Airway ranking to histamine was similar except that Emax of fetal bronchus and bronchiole were least. In parenchymal strips, mature animals gave strong responses to carbachol and histamine compared with other age groups. Sensitivity to carbachol was increased in the suckling trachea; otherwise it did not vary with age. Chemically skinned tracheal fibers exhibited three- to fourfold greater sensitivity to Ca2+ in fetal and suckling airways compared with the older animals. It is concluded that maturation of smooth muscle occurs in the expression of myosin, in the Ca2(+)-force relationships of the contractile machinery, and in the pharmacological responsiveness of the intact smooth muscle, with the latter greatest at or soon after birth.

In this study, isovolumic bronchial segments and bronchial rings were used to investigate the influence of airway diameter on smooth muscle force generation and acetylcholine responsiveness.Segments with internal diameters ranging from 1.0-6.0 mm were obtained from the mainstem bronchus of eight pigs. Responses to increasing acetylcholine concentrations were quantified in segments by intralumenal pressure (cmH 2 O), and in rings by tension (g·cm -1 ). The negative log of the concentration producing half the maximal effect (EC50) (i.e. pD 2 ) to acetylcholine was calculated for each segment and ring. Ring tension was used to calculate a theoretical lumen pressure for each ring, and this, along with the pD 2 , was compared with values obtained from segments of the same diameter.Intermediate-sized segments produced significantly greater intralumenal pressures than did large or small segments. Small segments were 160 times more sensitive to acetylcholine than large segments. In contrast to the segments, bronchial rings showed no effect of size on acetylcholine sensitivity. Theoretical ring lumen pressures matched those measured for large and intermediate segments, but not for small segments.The different behaviour of bronchial segments and rings obtained from the same sized airway suggests that the three-dimensional architecture of the airway is an important factor in determining behaviour, particularly in small airways.

Mucosal trypsin, a protease-activated receptor (PAR) stimulant, may have an endogenous bronchoprotective role on airway smooth muscle. To test this possibility the effects of lumenal trypsin on airway tone in segments of pig bronchus were tested.Bronchial segments from pigs were mounted in an organ chamber containing Kreb's solution. Contractions were assessed from isovolumetric lumen pressure induced by acetylcholine (ACh) or carbachol added to the adventitia.Trypsin, added to the airway lumen (300 mg?mL), had no immediate effect on smooth muscle tone but suppressed ACh-induced contractions after 60 min, for at least 3 h. Synthetic activating peptides (AP) for PAR 1 , PAR 2 or PAR 3 were without effect, but PAR 4 AP caused rapid, weak suppression of contractions. Lumenal thrombin was without effect and did not prevent the effects of trypsin. Effects of trypsin were reduced by N w -nitro-L-arginine methyl ester but not indomethacin. Trypsin, thrombin and PAR 4 AP released prostaglandin E2. Adventitially, trypsin, thrombin and PAR 4 AP (but not PAR 2 AP) relaxed carbachol-toned airways after ,3 min.The findings of this study show that trypsin causes delayed and persistent bronchoprotection by interacting with airway cells accessible from the lumen. The signalling mechanism may involve nitric oxide synthase but not prostanoids or protease-activated receptors.