Molecular biological considerations in cerebral vasospasm following aneurysmal subarachnoid hemorrhage

Abstract

<jats:p>Chronic delayed cerebral vasospasm (CDCV) remains a serious and often fatal complication of aneurysmal subarachnoid hemorrhage (SAH). The current understanding of its fundamental mechanisms and molecular biological characterization is rudimentary. Two important vasoactive substances have been implicated in CDCV: endothelin-1 (ET-1) and nitric oxide (NO). A 21-amino acid vasoconstrictor peptide, ET-1 has generated interest as a possible important contributor to cerebral vasospasm on the basis of both clinical and experimental evidence suggesting abnormally enhanced production. Nitric oxide is a cell membrane-permeable free radical gas that accounts for the vasodilatory effect of endothelium-derived relaxation factor and is a physiological antagonist of ET-1. As with ET-1, abnormalities of NO production have been implicated in several pathological conditions including cerebral vasospasm. This brief report reviews some of the physiological and regulatory features of these two molecules and explores the possibility of their relationship to cerebral vasospasm.</jats:p>

Safety of Intrathecal Sodium Nitroprusside for the Treatment and Prevention of Refractory Cerebral Vasospasm and Ischemia in Humans

“…30 -33 If ET-1 and NO are important factors in maintaining a dynamic equilibrium in vasomotor tone, the liberation of oxyhemoglobin from erythrocytes spilled into the subarachnoid space by SAH might be expected to result in a profound disequilibrium between the vasomotor effects of these molecules, resulting in unmitigated vasoconstriction. 24 That DCV is a substrate-driven phenomenon characterized by delayed availability and exhaustibility of the substrate and susceptible to being overwhelmed by repletion of NO is suggested by its limited time course and its possible response to exogenously administered NO. The delayed liberation of oxyhemoglobin by lysis of erythrocytes after SAH may provide a partial explanation for the delay almost uniformly observed in DCV.…”

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

“…Furthermore, although SAH does not modify the effect of nonendothelial NO, the absence of endothelial NO after SAH may contribute to the hyperreactivity of cerebral arteries to ET-1 and, thereby, to the development of cerebral vasospasm (Alabadí et al, 1997). Regulatory features of NO and ET-1 and the possibility of their relationship to SAH are reviewed in a brief report (Thomas, 1997). In basilar artery rings obtained from rats with SAH, relaxation to the selective ET B receptor agonist sarafotoxin 6c was reduced compared with that in artery rings from shamoperated rats, whereas endothelium-dependent ACh-induced relaxation was not altered.…”

Endothelial Nitric Oxide Synthase Tagging Single Nucleotide Polymorphisms and Recovery From Aneurysmal Subarachnoid Hemorrhage

“…After SAH, eNOS function is impaired in cerebral vessels (Iuliano et al, 2004), limiting any increase in vessel relaxation induced by the eNOS-associated increase in NO production. Administration of NO donors and NOS metabolites have shown efficacy in decreasing angiographic CV (Afshar, Pluta, Boock, Thompson, & Oldfield, 1995; Hino et al, 1996; Pluta, Oldfield, & Boock, 1997; Thomas, 1997; Thomas & Rosenwasser, 1999; Thomas et al, 1999; Tierney et al, 2001). However, the transformation of these clinical trials into widespread clinical treatment was limited by the short half-life of NO, side effects and potential toxicity (Afshar et al, 1995; Dietrich & Dacey, 2000; Hino et al, 1996).…”