Ontogenic changes in porcine pulmonary vascular and airway smooth muscle responsiveness in vitro

A marked decrease in pulmonary vascular resistance occurs in the newborn period, and a decrease in susceptibilty to bronchospasm occurs with maturation in humans. Both of these processes may be related to changes in the responsiveness of the smooth muscle to constricting and relaxing mediators. The goals of these studies were to determine if maturational changes occurred in the responsiveness of airway and vascular porcine smooth muscle in vitro. Studies were performed using pigs ranging in age from newborn to adult. Rings of pulmonary artery with and without endothelium, and tracheal smooth muscle strips or bronchial rings were suspended in organ baths filled with physiological salt solution, maintained at 37°C, and bubbled with 95%C>2 5%C02- Tissues were stretched to their optimal length for force development, and then concentration-response curves to a variety of agonists obtained.Pulmonary arteries from immature pigs were less responsive than those from adult pigs to adrenoreceptor mediated vasoconstriction. An alpha-2 adrenoreceptor mediated release of endothelium-derived relaxing factor was demonstrated in pulmonary arteries from adult pigs but not in those from immature pigs. Arteries from immature pigs were less responsive to relaxation induced by nitric oxide and hypoxia but not by sodium nitroprusside. Bronchial rings from immature pigs produced greater force (normalised to wet weight) in response to acetylcholine or potassium chloride than did rings from adult pigs, although the concentration of acetycholine required to produced half-maximal response (EC50) was similar. Rings from newborn pigs were more sensitive to the bronchodilator ketamine than those from adult pigs, as manifested by a shift in EC50. The relaxant action of ketamine on tracheal smooth muscle was shown to be due to an inhibitory effect on excitation of the postsynaptic nicotinic receptors of the intramural parasympathetic ganglion and a direct effect on the smooth muscle cell. Nonadrenergic noncholinergic innervation was shown to be present from birth. Hypoxic bronchodilation was seen in bronchial rings from all ages. In conclusion, this study demonstrates age-related changes in the in vitro responsiveness of both pulmonary vascular and airway smooth muscle to contractile and relaxant agonists, responses depending not only upon the agonist used to elicit contraction or relaxation, but also upon the age of the animal studied