AJP - Heart and Circulatory Physiology, Vol 253, Issue 2 234-H239, Copyright © 1987 by American Physiological Society
Selective inhibition of endothelium-dependent dilation in resistance-sized vessels in vivo
U. Pohl, L. Dezsi, B. Simon and R. Busse
In vivo experiments were performed in autoperfused hindlimbs of rabbits to
investigate the role of endothelium-mediated vasomotion in resistance-sized
vessels. The flow responses to the vasodilators acetylcholine (ACh), ATP,
and substance P (SP), all of which have been shown to act in an
endothelium-dependent manner in large conduit arteries, were studied before
and after exposure of the hindleg vasculature to gossypol (a potent
inhibitor of endothelium-mediated vasodilation in vitro). The flow
responses to adenosine (ADO), nitroglycerin (GTN), and prostaglandin E2
(PGE2), which induce relaxation by a direct effect on vascular smooth
muscle, were tested in the same manner. All vasodilators induced
dose-dependent increases in femoral flow up to two- to threefold when
administered intra-arterially. After gossypol, the flow responses to the
endothelium-dependent compounds (ACh, ATP, and SP) were severely reduced
(by 88 +/- 3%, P less than 0.01) or sometimes were converted to
constrictions (ATP). The flow increases induced by ADO, PGE2, and GTN
remained largely unaffected. Sham treatment (gossypol solute only),
exposure to indomethacin (10 microM), and ganglionic blockade had no
differential effect on the flow responses. The selective action of gossypol
in suppressing the flow responses to the endothelium-dependent compounds
ACh, ATP, and SP is consistent with a vasomotor role for endothelial cells
in resistance-sized vessels in vivo.
