This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stenman, E. Articles by Edvinsson, L. Search for Related Content PubMed PubMed Citation Articles by Stenman, E. Articles by Edvinsson, L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Acute Cerebral Infarction Brain Circulation and Metabolism Pathology of Stroke

(Stroke. 2002;33:2311.)
© 2002 American Heart Association, Inc.

Original Contributions

Cerebral Ischemia Upregulates Vascular Endothelin ET_B Receptors in Rat

Emelie Stenman, MSc; Malin Malmsjö, MD, PhD; Erik Uddman, MD; Gunilla Gidö, PhD; Tadeuz Wieloch, MD, PhD Lars Edvinsson, MD, PhD

From the Division of Experimental Vascular Research, Department of Internal Medicine (E.S., M.M., E.U., L.E.), and Division of Experimental Brain Research, Department of Clinical Neuroscience (G.G., T.W.), Lund University Hospital, Lund, Sweden.

Correspondence to Emelie Stenman, Division of Experimental Vascular Research, Lund University Hospital, Wallenberg Neurocentrum, 3 tr, Sölvegatan 17, 221 84 Lund, Sweden. E-mail Emelie.Stenman{at}med.lu.se, emelie_ahlrot@hotmail.com

Background and Purpose— Elevated levels of endothelin-1 (ET-1) have been reported in cerebral ischemia. A role for ET may prove more important if the vascular receptors were changed. We addressed whether there is any change in ET receptor expression in cerebral ischemia.

Methods— The right middle cerebral artery (MCA) was occluded in male Wistar rats for 2 hours with the intraluminal filament method. The basilar artery and both MCAs were removed after 46 hours of recirculation. The contractile responses to ET-1, a combined ET_A and ET_B receptor agonist, and sarafotoxin 6c (S6c), a selective ET_B receptor agonist, were examined in vitro, and ET receptor mRNA was quantified by real-time polymerase chain reaction.

Results— S6c, which had no contractile effect per se on fresh or sham-operated rat cerebral arteries, induced a marked contraction in the occluded MCA (E_max [maximum contraction, calculated as percentage of the contractile capacity of 63.5 mmol/L K⁺]=68±68%; P<0.0001), while there was no difference in the responses to ET-1 after cerebral ischemia. Real-time polymerase chain reaction revealed a significant upregulation of both the ET_A and ET_B receptors (both P<0.05) in the occluded MCA compared with the nonoccluded MCA from the same rats.

Conclusions— Focal cerebral ischemia in rat induces increased transcription of both ET_A and ET_B receptors, which results in the appearance of a contractile response to the ET_B receptor agonist S6c. These results suggest a role for ET receptors in the pathogenesis of a vascular component after cerebral ischemia.

Key Words: cerebral ischemia • endothelins • middle cerebral artery • receptors, endothelin • rats

This article has been cited by other articles:

				X.-K. Tong and E. Hamel Transforming Growth Factor-beta1 Impairs Endothelin-1-Mediated Contraction of Brain Vessels by Inducing Mitogen-Activated Protein (MAP) Kinase Phosphatase-1 and Inhibiting p38 MAP Kinase Mol. Pharmacol., December 1, 2007; 72(6): 1476 - 1483. [Abstract] [Full Text] [PDF]

				J. Konczalla, H. Vatter, S. Weidauer, A. Raabe, and V. Seifert Alteration of the cerebrovascular function of endothelin B receptor after subarachnoidal hemorrhage in the rat. Experimental Biology and Medicine, June 1, 2006; 231(6): 1064 - 1068. [Abstract] [Full Text] [PDF]

				R. Jamali and L. Edvinsson Involvement of protein kinases on the upregulation of endothelin receptors in rat basilar and mesenteric arteries. Experimental Biology and Medicine, April 1, 2006; 231(4): 403 - 411. [Abstract] [Full Text] [PDF]

				A. Y. Shih, P. Li, and T. H. Murphy A Small-Molecule-Inducible Nrf2-Mediated Antioxidant Response Provides Effective Prophylaxis against Cerebral Ischemia In Vivo J. Neurosci., November 2, 2005; 25(44): 10321 - 10335. [Abstract] [Full Text] [PDF]

				Y. Zhou, W. P. Dirksen, J. L. Zweier, and M. Periasamy Endothelin-1-induced responses in isolated mouse vessels: the expression and function of receptor types Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H573 - H578. [Abstract] [Full Text] [PDF]

				E. Stenman and L. Edvinsson Cerebral Ischemia Enhances Vascular Angiotensin AT1 Receptor-Mediated Contraction in Rats Stroke, April 1, 2004; 35(4): 970 - 974. [Abstract] [Full Text] [PDF]

				M. Henriksson, E. Stenman, and L. Edvinsson Intracellular Pathways Involved in Upregulation of Vascular Endothelin Type B Receptors in Cerebral Arteries of the Rat Stroke, June 1, 2003; 34(6): 1479 - 1483. [Abstract] [Full Text] [PDF]