Effects of Amiloride and Na Selenite on the ATPase Levels, Malondialdehyde Levels, and on Superoxide Dismutase Activity and the Histopathologic Findings After Subarachnoid Hemorrhage in the Pigs

ObjectivesCerebral vasospasm after subarachnoid hemorrhage (SAH) is a reversible arterial narrowing occurring as a result of the mechanical and physiologic effects of blood products. Multiple factors are effective in the development of arterial narrowing; they provide long-term arterial contraction, inhibition of vasodilatation, and depression of the metabolic, immunoreactive, and inflammatory processes. We assessed Na selenite, which activates calpain II and promotes intracellular Ca2+ influx, by increasing oxygen radical synthesis in SAH. We also assessed amiloride, which involves non–voltage-graded Na channels, Na+/Ca2+ exchange, and Na+/H+ antiport mechanism and antioxidative effects. We evaluated the morphologic and biochemical effects of Na selenite and amiloride on basilar arterial smooth muscle vessels in SAH. MethodsTwenty pigs were randomly allocated to 4 groups. In group 1 only SAH was created. In group 2, after SAH, subcutaneously amiloride was applied once a day for 4 weeks. In group 3, after SAH subcutaneous Na selenite was applied once a day for 4 weeks. In group 4, after SAH, amiloride and Na+ selenite were given subsequently once a day for 4 weeks. The effects of amiloride and Na selenite on the ATPase and malondialdehyde (MDA) levels, and on Superoxide dismutase activity (SOD), and the resulting histopathologic findings were studied. ResultsIn group 2, the vessel SOD level was 3 times higher than in group 1, but the Na+ K+ ATPase and MDA levels were found to be similar. In group 3, SOD activity was found to be similar to that in group 1. but Na+ K+ ATPase and MDA levels were 3 times higher than group 1. In group 4, SOD activity was very high in comparison with groups 3 and 1, whereas MDA level was half that found in group 3. ATPase levels did not show a significant difference from those in group 2. ConclusionsThese results demonstrate that amiloride is not effective in basilar arterial changes due to SAH. However, amiloride protects the side effects of Na+ selenite. We suggest that this protection occurs by blocking the effect of Na+ selenite on oxidation and on the Ca2+ influx mechanism.

[1]  D. Bers,et al.  Normal and abnormal calcium homeostasis , 2005 .

[2]  B. Meyer,et al.  803 Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage Is Inhibited by Clazosentan, an Endothelin Receptor Antagonist. , 2005, Neurosurgery.

[3]  E. Cragoe,et al.  Amiloride and its analogs as tools in the study of ion transport , 1988, The Journal of Membrane Biology.

[4]  Ivana Oštádalová,et al.  Cataract induced by administration of a single dose of sodium selenite to suckling rats , 1978, Experientia.

[5]  I. Laher,et al.  Signaling mechanisms in cerebral vasospasm. , 2005, Trends in cardiovascular medicine.

[6]  N. Kassell,et al.  Editorial: Unruptured aneurysms , 2002 .

[7]  D. Piepgras Unruptured aneurysms. , 2002, Journal of neurosurgery.

[8]  G. Yılmaz,et al.  Prevention of selenite-induced opacification and biochemical changes in the rat pup lens through amiloride pretreatment. , 2000, Current eye research.

[9]  G. Svegliati-Baroni,et al.  The Na+/H+ exchanger modulates the fibrogenic effect of oxidative stress in rat hepatic stellate cells. , 1999, Journal of hepatology.

[10]  Charles Tator,et al.  Normal and abnormal calcium homeostasis in neurons: a basis for the pathophysiology of traumatic and ischemic central nervous system injury. , 1996, Neurosurgery.

[11]  J. Findlay Perioperative Management of Subarachnoid Hemorrhage , 1995 .

[12]  H. Garty Molecular properties of epithelial, amiloride‐blockable Na+ channels , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[13]  S. Ohta,et al.  Changes in Ca(++)-ATPase activity in smooth-muscle cell membranes of the canine basilar artery with experimental subarachnoid hemorrhage. , 1994, Journal of neurosurgery.

[14]  J. L. Hess,et al.  Selenite and Ca2+ homeostasis in the rat lens: effect on Ca-ATPase and passive Ca2+ transport. , 1993, Current eye research.

[15]  J. Zadunaisky,et al.  A Na+/H+ exchanger and its relation to oxidative effects in plasma membrane vesicles from lens fibers. , 1992, Experimental eye research.

[16]  J. L. Hess,et al.  Calcium efflux in rat lens: Na/Ca-exchange related to cataract induced by selenite. , 1992, Current eye research.

[17]  Stephen Bannister,et al.  Analysis of rat lens 45Ca2+ fluxes: evidence for Na(+)-Ca2+ exchange. , 1991, Experimental eye research.

[18]  Y. Nozawa,et al.  Cytosolic calcium changes in cultured rat aortic smooth-muscle cells induced by oxyhemoglobin. , 1991, Journal of neurosurgery.

[19]  P. Ades 522 pages R.H. Wilkins Cerebral vasospasm , 1989, Neurophysiologie Clinique/Clinical Neurophysiology.

[20]  J. Peterson,et al.  Immunological reaction against the aging human subarachnoid erythrocyte. A model for the onset of cerebral vasospasm after subarachnoid hemorrhage. , 1989, Journal of neurosurgery.

[21]  K. Hightower,et al.  Effects of selenium on ion homeostasis and transparency in cultured lenses. , 1989, Investigative ophthalmology & visual science.

[22]  T. Shearer,et al.  Selenite cataract: a review. , 1987, Current eye research.

[23]  W. Rathbun,et al.  Inhibition of Na,K-ATPase by sodium selenite and reversal by glutathione. , 1986, Current eye research.

[24]  H. Nishigori,et al.  An animal model for cataract research: cataract formation in developing chick embryo by glucocorticoid. , 1983, Experimental eye research.

[25]  V. Reddy,et al.  Interactions of glutathione disulfide with lens crystallins. , 1982, Current eye research.

[26]  B. Weir Medical Aspects of the Preoperative Management of Aneurysms: A Review , 1979, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[27]  K. Yagi,et al.  Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. , 1979, Analytical biochemistry.

[28]  J. Harding,et al.  Free and protein-bound glutathione in normal and cataractous human lenses. , 1970, The Biochemical journal.

[29]  I. Fridovich,et al.  Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). , 1969, The Journal of biological chemistry.

[30]  A C Dornhorst,et al.  Review of Medical Physiology. , 1966 .

[31]  J. Kinoshita SELECTED TOPICS IN OPHTHALMIC BIOCHEMISTRY. , 1963, Archives of ophthalmology.

[32]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.