Am. J. Respir. Crit. Care Med., Vol 150, No. 5, 11 1994, 1402-1410.
NADPH-diaphorase activity as a marker for nitric oxide synthase in neurons of the guinea pig respiratory tract
T Shimosegawa and T Toyota
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Recent studies in physiology have suggested that part of the inhibitory
nonadrenergic noncholinergic (iN-ANC) response of airway smooth muscle is
mediated by nitric oxide (NO). To examine this point morphologically, the
guinea pig respiratory tract was investigated histochemically for
nicotinamide adenine dinucleotide phosphate (NADPH)- diaphorase (NADPH-d),
a marker for NO synthase (NOS). In addition, coexpression of NOS and
vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide
(CGRP) was studied using a combination of histochemistry for NADPH-d and
immunohistochemistry for VIP or CGRP. Nerve fibers showing NADPH-d activity
were abundantly observed in the respiratory tract. They were distributed
throughout smooth-muscle bundles, lamina propria, submucosal glands, and
around bronchial and pulmonary arteries. NADPH-d-containing nerve-cell
bodies were occasionally found within airway ganglia. The colocalization
study demonstrated that NADPH-d-containing nerve fibers frequently
coincided with VIP-like immunoreactive nerve fibers but not with CGRP-like
immunoreactive nerve fibers. Among nonneural tissues, NADPH-d activity was
noticed in the endothelium of both bronchial and pulmonary vessels, and in
the pleura. These observations indicated that NO may be produced by neurons
and vascular endothelium of the guinea pig respiratory tract, and may
function as a neuronal mediator as well as endothelium- derived relaxing
factor (EDRF). Colocalization of NADPH-d and VIP-like immunoreactivity in
nerve fibers suggested that NO and VIP may function as cotransmitters.
