Am. J. Respir. Crit. Care Med., Vol 154, No. 3, Sep 1996, 629-632.
Nonadrenergic noncholinergic relaxation of human pulmonary arteries is partially mediated by nitric oxide
JA Scott, I Craig and DG McCormack
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
Nonadrenergic noncholinergic (NANC) vasodilator mechanisms may contribute
to the maintenance of low vascular resistance characteristic of the
pulmonary circulation. Previous studies have demonstrated that nitric oxide
(NO) is the principal NANC neurotransmitter in guinea pig pulmonary
arteries. We examined whether NANC relaxation could be demonstrated in
human pulmonary arteries, and the role of NO in this phenomenon. Fresh
human pulmonary artery rings, with and without an intact endothelium, were
mounted in organ baths containing Krebs' solution and precontracted with
U44069 (0.3 microM). Adrenergic and cholinergic neurotransmitter pathways
were blocked with guanethidine and atropine, respectively (10 microM each).
In both endothelium-intact and -denuded vessels, electrical field
stimulation (EFS, 1 to 10 Hz, 100 V) resulted in a frequency-dependent
relaxation (maximal relaxation of 25 +/- 4% and 15 +/- 2% in
endothelium-intact and -denuded vessels, respectively). Tetrodotoxin (0.3
microM) abolished the EFS-induced relaxation. L-NG-nitro-arginine methyl
ester (L-NAME, 10 microM), was used to block enzymatic synthesis of NO. In
both endothelium-intact and -denuded vessels, L-NAME reduced NANC
relaxation to approximately 50% of control values. This reduction was
reversible with the application of L-arginine (100 microM). We conclude
that NANC relaxation exists in human pulmonary arteries and that it is
partly mediated through NO.
