Early maturation of force production in pig tracheal smooth muscle during fetal development

The contractility of airway smooth muscle is fully established at late term at birth but its responsiveness during fetal life has not been defined. In this study, the contractile force of airway smooth muscle to acetylcholine (ACh), K+ depolarizing solution, and electrical field stimulation (EFS) was measured in tracheas from small fetal pigs. Contraction to either agonist and to EFS was detectable in fetuses of as low as 9 g body weight, which corresponds to approximately 36 days of gestation. Isometric force increased progressively with age, reaching 4.1 +/- 0.4 mN for K+ and 5.8 +/- 0.5 mN for ACh (10(-4) M) at 600 g fetal weight (90 days). However, when normalized for cross sectional area of smooth muscle, the stress was essentially the same from 17- to 600-g fetuses. (K+: 17 g = 74.4 +/- 10.6 mN/mm2, 600 g = 89.3 +/- 13.0 mN/mm2; ACh [10(-4) M]: 17 g = 76.3 +/- 16.0 mN/mm2, 600 g = 127.0 +/- 13.0 mN/mm2). The sensitivities of the various groups to ACh were not significantly different (e.g., EC50: 30 g = 4.0 +/- 0.2 x 10(-6) M, 600 g = 3.7 +/- 1.1 x 10(-6) M). EFS produced frequency-dependent contractile responses in all groups. With increasing fetal size, there was a corresponding increase in force. When this force was normalized to a maximum ACh response (10(-4) M), there was no significant difference between groups of fetuses. Histologic examination showed the major tissue components of the trachea were present in fetuses above 7 g. Immunocytochemistry detected myosin, caldesmon, and filamin in the smooth muscle from fetuses of 7 g and above, showing that contractile and actin-binding proteins were present from a very early age. It is concluded that smooth muscle contractile function is well developed very early in fetal life in pigs.