Gn. Colasurdo et al., MATURATION OF NONADRENERGIC NONCHOLINERGIC INHIBITORY SYSTEM IN NORMAL AND ALLERGEN-SENSITIZED RABBITS, American journal of physiology. Lung cellular and molecular physiology, 11(6), 1994, pp. 120000739-120000744
We investigated the functional existence of the nonadrenergic noncholi
nergic inhibitory (NANCi) system in developing rabbit airways in vitro
. Furthermore, we evaluated the effect of parenteral exposure to a spe
cific allergen (ragweed) on the maturation of this neural pathway. NAN
Ci responses were studied on tracheal smooth muscle (TSM) segments obt
ained from normal and ragweed-sensitized New Zealand White rabbits at
1, 2, 4, and 12 wk of age. The TSM segments were removed and placed in
tissue baths containing modified Krebs-Henseleit solution, atropine (
1 x 10(-5) M), and propranolol (5 x 10(-6) M). After contraction with
neurokinin A (1 x 10(-5) M), electrical field stimulation was applied
at stimulation frequencies ranging from 5 to 30 Hz to determine the fr
equency that produced maximal relaxation. The NANCi response to EFS wa
s measured and expressed as the mean (+/-SE) percent relaxation at 20
Hz, because this stimulation frequency gave the maximal NANCi response
at each age studied. TSM segments obtained from control rabbits at 1
wk of age did not demonstrate a NANCi response at the frequencies of s
timulation used. By contrast, a reproducible NANC relaxation was demon
strated in TSM from 2-, 4-, and 12-wk-old rabbits. The magnitude of th
is response was 27 +/- 4.7 (n = 10), 29 +/- 4.8 (n = 9), and 37 +/- 4%
(n = 18), respectively. The same experiments performed on TSM segment
s obtained from ragweed-sensitized animals gave significantly decrease
d values of NANCi response. In 2-, 4-, and 12-wk-old rabbits, the NANC
i responses were 11.5 +/- 3.4 (n = 9), 11 +/- 2 (n = 13), and 16 +/- 4
.2% (n = 14). Again, no NANC relaxation was present at 1 wk of age. Th
ese findings suggest that NANCi innervation is not functional at birth
and undergoes considerable postnatal development. Furthermore, the ma
turation of the NANCi system is impaired in ragweed-sensitized rabbits
. This early dysfunction may disrupt the airways' neural control and c
ontribute to the development of altered airways function.