Decreased endothelium-dependent relaxation in subarachnoid hemorrhage-induced vasospasm: role of ET-1.
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 3 days following injection of autologous arterial blood into the rabbit cisterna magna compared with vessels from control rabbits. In situ suffusion with the endothelium-dependent relaxant, acetylcholine (ACh; 10 microM), 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, BQ-123 (1 microM), 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 endothelin-1 (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.
Zuccarello
M
M
Department of Neurosurgery, University of Cincinnati College of Medicine, Ohio 45267, USA.
Romano
A
A
Passalacqua
M
M
Rapoport
R M
RM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016232:Endothelins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D014661:Vasoconstriction; D014664:Vasodilation
D016232:Endothelins; D010456:Peptides, Cyclic; D012701:Serotonin; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)