Abstract
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.
