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. CONCLUSION: 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.