Sustained arterial narrowing after prolonged exposure to perivascular endothelin.
OBJECTIVE
The vasoconstrictor peptide endothelin-1 (ET-1) produces narrowing of cerebral arteries and has been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. Little is known, however, regarding the physiological consequences of prolonged exposure of arterial wall to ET-1.


METHODS
In 30 rats, normal saline or 10(-8) mol/h of ET-1 was continuously applied for 3 or 5 days to the adventitial surface of the femoral artery in a Silastic cuff via an osmotic infusion pump. Vessels were examined for histopathological changes and luminal narrowing during ET-1 infusion (3 or 5 d) or at intervals from 2 to 9 days after infusion was stopped.


RESULTS
Marked arterial constriction (30-40% arterial diameter reduction) was present during continuous ET-1 infusion for 3 or 5 days. For both 3- and 5-day ET-1 infusions, significant reduction in arterial cross sectional area persisted up to 4 days after cessation of infusion, after which normal caliber returned. In arteries with persistent luminal narrowing after cessation of ET-1 infusion, light microscopic findings revealed morphological changes in the vessel wall similar to those observed in cerebral vasospasm after subarachnoid hemorrhage, with apparent increased collagen deposition in media and adventitia.


CONCLUSIONS
Continuous infusion of ET-1 produces reversible arterial narrowing that persists beyond the usual interval of physiological effect for this agent. Prolonged arterial constriction may produce physiological changes in arterial wall that act to maintain a narrowed lumen.
Ahn
Young Min
YM
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington, USA.
Gajdusek
Corinne
C
London
Susan
S
Moon
Chang Taek
CT
Oh
Chang Wan
CW
Mayberg
Marc R
MR
D000818:Animals; D002536:Cerebral Arteries / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014661:Vasoconstriction
D019332:Endothelin-1