Decreased endothelium-dependent relaxation in subarachnoid
hemorrhage-induced vasospasm: role of endothelin-1.
Zuccarello, Mario, Alberto Romano, Marcello Passalacqua, and Robert M.
Rapoport.
Departments of Neurosurgery and Pharmacology and Cell Biophysics,
and Veterans Affairs Medical Center, University of Cincinnati College
of Medicine, 231 Bethesda Avenue, Cincinnati, Ohio 45267
APStracts 2:0209H, 1995.
The purpose of this study was to test whether endothelium-dependent
relaxation is decreased during acute vasospasm following subarachnoid
hemorrhage (SAH), and the mechanism underlying the decrease. Basilar
artery in situ was 35% constricted three days following injection of
autologous arterial blood into the rabbit cisterna magna, as compared
to vessels from control rabbits. In situ suffusion with the
endothelium-dependent relaxant, acetylcholine (ACh; 10[mu]M), relaxed
resting and serotonin (5-HT)-contracted control vessels, but not
vasospastic and 5-HT-contracted vasospastic vessels. In contrast, the
relaxant potency, and efficacy, of ACh was similar in control and
vasospastic vessels contracted with 5-HT in vitro. In situ suffusion
with the ETA receptor antagonist, BQ123 (1 [mu]M), reversed the
vasospasm by 51%, and restored the magnitude of ACh relaxation of
vasospastic and 5-HT-contracted vasospastic vessels to that of
controls. ACh in situ and in vitro relaxed ET-1-contracted control
vessels to a smaller magnitude than 5-HT-contracted control vessels.
These results suggest, in contrast to previous studies, that
endothelium-dependent relaxation is decreased during acute vasospasm
following SAH. The decreased endothelium-dependent relaxation is
secondary to the underlying ET-1-mediated spasm. The inhibition of
endothelium-dependent relaxation observed in situ following SAH
cannot be demonstrated in vitro, presumably due to loss of the ET-1
-mediated vasospasm.
Received 17 October 1994; accepted in final form 24 March 1995.
APS Manuscript Number H926-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.