This Article Full Text 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 Rosenblum, W. I. Articles by Wormley, B. Search for Related Content PubMed PubMed Citation Articles by Rosenblum, W. I. Articles by Wormley, B.

(Stroke. 1995;26:1877-1882.)
© 1995 American Heart Association, Inc.

Articles

Selective Depression of Endothelium-Dependent Dilations During Cerebral Ischemia

William I. Rosenblum, MD Brandon Wormley, BS

From the Department of Pathology (Neuropathology), Medical College of Virginia/Virginia Commonwealth University, Richmond.

Background and Purpose Pial arterioles have diverse mechanisms for endothelium-dependent dilations. In mice, different mechanisms or endothelium-derived mediators exist for each of the following dilators: acetylcholine, bradykinin, and calcium ionophore A-23187. This study tests the response to each of these dilators during profound ischemia. The response to sodium nitroprusside, an endothelium-independent dilator, was also tested.

Methods In each mouse, ischemia was produced by bilateral carotid artery ligation that reduced cortical blood flow by approximately 90% as determined by laser-Doppler flowmetry. In separate studies of 10 mice each, dilations of pial arterioles to two doses of each dilator were compared before and after 10 minutes of occlusion, with the occlusion continuing during the second set of measurements. The dilator was applied in the suffusate bathing the pial surface exposed at a craniotomy site. Diameters were monitored by in vivo television microscopy and image splitting.

Results The dose-dependent dilations to acetylcholine, bradykinin, and calcium ionophore A-23187 were each profoundly depressed during ischemia. The response to sodium nitroprusside was not depressed. In all cases, the ischemia was accompanied by arteriolar narrowing of approximately 25% and by obvious slowing of blood flow observed by intravital microscopy. Superoxide dismutase plus catalase failed to prevent the depressed response to acetylcholine.

Conclusions Endothelium-dependent dilations, mediated by diverse endothelium-derived relaxing factors, are depressed during ischemia of 10 to 15 minutes' duration. This cannot be a nonselective effect on vessel responsivity caused by constriction, reduced flow, or reduced intraluminal pressure during ischemia because under the same conditions dilation to endothelium-independent sodium nitroprusside is preserved. The selective endothelial dysfunction may play a role in exacerbating ischemia by precluding the ability of some dilators, released during ischemia, to dilate the resistance vessels.

Key Words: acetylcholine • bradykinin • cerebral ischemia • endothelium-derived relaxing factor • mice

This article has been cited by other articles:

				N. Baudry, E. Laemmel, and E. Vicaut In vivo reactive oxygen species production induced by ischemia in muscle arterioles of mice: involvement of xanthine oxidase and mitochondria Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H821 - H828. [Abstract] [Full Text] [PDF]

				Y. Watanabe, M. T. Littleton-Kearney, R. J. Traystman, and P. D. Hurn Estrogen restores postischemic pial microvascular dilation Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H155 - H160. [Abstract] [Full Text] [PDF]

				J. M. Gidday, T.S. Park, A. R. Shah, E. R. Gonzales, P. M. Kochanek, R. S.B. Clark, and M. J. Whalen Modulation of Basal and Postischemic Leukocyte-Endothelial Adherence by Nitric Oxide • Editorial Comment Stroke, July 1, 1998; 29(7): 1423 - 1430. [Abstract] [Full Text] [PDF]

				W. I. Rosenblum and W. M. Armstead Selective Impairment of Response to Acetylcholine After Ischemia/Reperfusion in Mice Stroke, February 1, 1997; 28(2): 448 - 452. [Abstract] [Full Text]