The Possible Role Of Urotensin Ⅱ In The Development Of Cerebral Vasospasm Following Subarachnoid Hemorrhage In Rats

Objective: Cerebral vasospasm is a persistent arterial narrowing typicallyobserved during the3-14days after subarachnoid hemorrhage (SAH).Vasospasm is frequently associated with ischemic neurological deficits or evendeath, resulting in a poor prognosis for patients with SAH. However, themechanism underlying cerebral vasospasm remains elusive, and no effectivetherapeutic strategies have been established.Intensive studies suggest that numerous factors were involved in thedevelopment of cvs, including oxyhaemoglobin, the imbalance between NO(nitrous oxide) and endothelin1, alteration in the structure of the vessel walland inflammatory reaction,while none of these factors can induce cvsindependly, the pathophysiologic mechanism appears to be a multifactorialprocess.Urotensin II (UII) is an11amino acid cyclic peptide originally isolatedfrom fish.It contains a amino acid sequence that is exceptionally conservedacross most species, UII and its receptor, GPRl4（or UT）, are widelyexpressed among the cardiovascular, pulmonary, central nervous,renal, andmetabolic systems in humans and in other animal species.UII is known for itsstrong vascular smooth muscle-dependent vasoconstriction. Binding with UT，UII exerts a wide range of actions in multiple systems, such as proliferation ofvascular smooth muscle cells, fibroblasts, and chemotaxis of inflammatorycells.The pathologic processes above are also involved in the development ofCVS after SAH，while whether UII is participate in the development hasn’tbeen reported.This study is to evaluate the possible role of UII in thedevelopment of CVS following subarachnoid hemorrhage in the rat.Methods: Thirty-six male albino Wistar rats, each weighing200-240g,were randomized into two groups.Group1(Normal group)(n=6) having no treatment; Group2(SAH group) induced by a rat double hemorrhage model,inwhich autologous arterial blood was injected into cisterna magna twice. TheSAH group were divided into5subgroups of3d (n=6),5d (n=6),7d (n=6),11d (n=6)and14d (n=6) after SAH, in which the rats were killed ondays3,5,7,11and14, respectively.At the diferent stage of SAH,cluminalperimeter and thickness of basilar artery was measured by H&Estaining,immunostaining were performed to detect the expression of UII inbasilar artery.Results: Compared with the normal group, the neurological state wassignificantly worse in rats with SAH. The pathological changes includingarterial narrowing,thickness of arterialwall could be seen on day3afterSAH,and reached to peak on day7,decreased on day11,and were similar tothe Normal group on day14. The elevated expression of UII was detected inthe basilar artery after SAH and peaked on day5-7,then decreased,beingsimilar to the Normal group on day14.The expression of UII was slight innormal group.Conclusion: The pathological changes including arterialnarrowing,thickness of arterialwall happened after SAH,vasospasm of thedouble-hemorrhage model accurately correlates with the time courses forvasospasm in humans,This is the first tudy finding UII expresses slightly innormal rat basilar artery and the expression greatly enhanced afterSAH,suggesting UII may play an important role in the occurrence anddevelopment of vasospasm after SAH.