AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 5 999-1003, Copyright © 1993 by American Physiological Society
Endothelium-derived factors modulate contraction of bronchial smooth muscle
A. J. McLarty, C. G. McGregor and V. M. Miller
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Experiments were designed to determine how changes in the ratio of specific
vascular endothelium-derived factors might affect reactivity of bronchial
smooth muscle. The epithelium was mechanically removed from rings of
third-order canine bronchi, and the rings were suspended in organ chambers
for measurement of isometric force. Rings of pulmonary artery were cut; in
some the endothelium was mechanically removed. The arterial rings were
everted and pairs, with and without endothelium, were incubated with
control solution, NG-monomethyl-L-arginine (L-NMMA), indomethacin, or both
L-NMMA and indomethacin for 90 min. They were then inserted into the lumen
of the bronchial rings. Cumulative concentration-response curves to
acetylcholine and 5-hydroxytryptamine were obtained. There was no
significant difference in response between bronchi containing arteries with
or without endothelium incubated with control solution. Contractions of
bronchi containing arteries without endothelium, incubated in either L-NMMA
or indomethacin, increased from control. However, in rings containing
arteries with endothelium, incubation with either inhibitor decreased
bronchial contractions. Incubation with both inhibitors eliminated the
difference. These results suggest that the vascular endothelium produces
factors that can both contract and relax bronchial smooth muscle. With
inhibition of production of either nitric oxide with L-NMMA or prostanoids
with indomethacin, release of other endothelium-derived factors occurs that
attenuates contractions of bronchial smooth muscle. Therefore, an imbalance
in the ratio of production of endothelium-derived factors may contribute to
bronchospastic disorders.
