11β-Hydroxysteroid Dehydrogenase Type II Inhibition Causes Cerebrovascular Remodeling and Increases Infarct Size after Cerebral Ischemia

作者: Jessica M. Osmond , Anne M. Dorrance

DOI: 10.1210/EN.2008-0808

关键词:

摘要: Direct mineralocorticoid receptor (MR) activation with deoxycorticosterone acetate has deleterious effects on the cerebral vasculature. Inhibition of 11beta-hydroxysteroid dehydrogenase type II (11betaHSD2) mimics detrimental elevated mineralocorticoids in heart, but effect enzyme inactivation vasculature is unknown. Therefore, we hypothesized that systemic 11betaHSD2 inhibition carbenoxolone (CBX) would cause remodeling middle artery (MCA) and increase damage caused by ischemia. Six-week-old male Sprague Dawley rats were divided into control CBX (2.5 mg/d) + 0.9% NaCl treated. After 4 wk treatment, used to assess either structure reactivity MCA or response ischemia using occlusion technique. Cerebral was assessed 2,3,5-triphenyltetrazolium chloride staining expressed as a percentage hemisphere infarcted. treatment increased systolic blood pressure (153.2 +/- 7.3 vs. 122.1 4.4 mm Hg; P < 0.05) compared rats. MCAs from treated smaller stiffer than over range intralumenal pressures, indicating inward vessel. significantly ischemic infarct size (27.1 5.4% 14.8 4.2%; 0.05). These data indicate 11betaHSD2, and, thus, disproportionate glucocorticoid MR, results worsens outcome ischemia, further underscoring importance understanding mechanism which MR leads cerebrovascular disease.

参考文章(38)
E. Rusvai, A. Náray-Fejes-Tóth, A new isoform of 11 beta-hydroxysteroid dehydrogenase in aldosterone target cells. Journal of Biological Chemistry. ,vol. 268, pp. 10717- 10720 ,(1993) , 10.1016/S0021-9258(18)82044-0
Peter Coyle, Donald D. Heistad, Development of collaterals in the cerebral circulation. Journal of Vascular Research. ,vol. 28, pp. 183- 189 ,(1991) , 10.1159/000158860
Yevgen Leshchenko, Sergei Likhodii, Wendy Yue, WilliamM Burnham, JoseL Perez Velazquez, Carbenoxolone does not cross the blood brain barrier: an HPLC study BMC Neuroscience. ,vol. 7, pp. 3- 3 ,(2006) , 10.1186/1471-2202-7-3
E. P. Gomez-Sanchez, C. E. Gomez-Sanchez, Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone American Journal of Physiology-endocrinology and Metabolism. ,vol. 263, ,(1992) , 10.1152/AJPENDO.2006.263.6.E1125
P. Coyle, Altered Cerebral Collaterals and Protection from Infarction Springer, Berlin, Heidelberg. pp. 69- 78 ,(1989) , 10.1007/978-3-642-85863-5_9
C.R.W. Edwards, D. Burt, M.A. Mcintyre, E.R. De Kloet, P.M. Stewart, L. Brett, W.S. Sutanto, C. Monder, LOCALISATION OF 11β-HYDROXYSTEROID DEHYDROGENASE—TISSUE SPECIFIC PROTECTOR OF THE MINERALOCORTICOID RECEPTOR The Lancet. ,vol. 332, pp. 986- 989 ,(1988) , 10.1016/S0140-6736(88)90742-8
Donald D. Heistad, William G. Mayhan, Peter Coyle, Gary L. Baumbach, Impaired Dilatation of Cerebral Arterioles in Chronic Hypertension Journal of Vascular Research. ,vol. 27, pp. 258- 262 ,(1990) , 10.1159/000158817
W. Reid Litchfield, Bruce F. Anderson, Ruediger J. Weiss, Richard P. Lifton, Robert G. Dluhy, Intracranial Aneurysm and Hemorrhagic Stroke in Glucocorticoid-remediable Aldosteronism Hypertension. ,vol. 31, pp. 445- 450 ,(1998) , 10.1161/01.HYP.31.1.445
Raymond A. Swanson, Matthew T. Morton, George Tsao-Wu, Robert A. Savalos, Charisse Davidson, Frank R. Sharp, A Semiautomated Method for Measuring Brain Infarct Volume Journal of Cerebral Blood Flow and Metabolism. ,vol. 10, pp. 290- 293 ,(1990) , 10.1038/JCBFM.1990.47
Ursula Kuhnle, Sabina Lewicka, Peter J. Fuller, Endocrine Disorders of Sodium Regulation Hormone Research in Paediatrics. ,vol. 61, pp. 68- 83 ,(2004) , 10.1159/000075242