AJP - Heart and Circulatory Physiology, Vol 249, Issue 1 95-101, Copyright © 1985 by American Physiological Society
Bioassay of endothelium-derived relaxing factor(s): inactivation by catecholamines
G. M. Rubanyi, R. R. Lorenz and P. M. Vanhoutte
A bioassay technique was developed to analyze the effect of vasoactive
substance(s) released from endothelial cells. Canine femoral arteries with
or without endothelium were perfused with physiological salt solution at 37
degrees C. The perfusate was bioassayed with a ring of coronary artery
without endothelium. A substance(s) released by the endothelial cells under
basal conditions caused relaxation of unstimulated coronary arteries or
relaxation of those contracted with prostaglandin F2 alpha. The release of
the relaxing substance(s) was augmented by acetylcholine. The relaxation
induced by acetylcholine was biphasic: an initial rapid phase followed by a
partial recovery and a slowly developing prolonged relaxation; the
half-life of the substance(s) causing the initial phase averaged 6.3 s.
Norepinephrine, epinephrine, and ascorbic acid, given downstream of the
femoral artery, reversibly prevented the second phase but only attenuated
the initial relaxation. These observations indicate that an
endothelium-derived relaxing substance(s) is released into the lumen of the
femoral artery under basal conditions and during stimulation with
acetylcholine. Catecholamines can inactivate the relaxing substance(s) but
do not prevent either its production by endothelial cells or its action on
vascular smooth muscle.
