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Response to Letter Regarding Article, “Association of Chronic Kidney Disease With Cerebral Microbleeds in Patients With Primary Intracerebral Hemorrhage”
We thank Dr Tsuda for his interest in our recently published article. As he alluded to in his letter, nitrous oxide exerts a powerful influence on the regulation of glomerular filtration rate,1 and mounting evidence suggests that initial renal endothelial damage may lead to superoxide scavenging of nitric oxide, ultimately leading to diffuse severe endothelial dysfunction, including within the cerebrovascular bed.2 However, it must be noted that results from various studies on endogenous nitric oxide conflict, with some studies suggesting a deficiency in nitric oxide with chronic kidney disease,3 and others reporting upregulated nitrous oxide production.4 About the possible interplay of chronic kidney disease, nitric oxide production, and race, reduced nitric oxide bioavailability in the vascular wall may indeed be an important contributor to the observed differences in function and mechanical properties of resistance arteries between blacks and whites,5 but we did not collect data on endothelial function or plasma NO-metabolite levels in the Differences in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) cohort and therefore cannot specifically address this issue directly in the current data set. We share Dr Tsuda’s enthusiasm for future studies aimed at exploring inadequate nitric oxide production as a potential explanation for racial disparities in the influence of chronic kidney disease on vascular brain injury (including cerebral microbleeds).
Disclosures None.
Bruce Ovbiagele, MD, MSc, MAS Department of Neurosciences Medical University of South Carolina Charleston, SC Chelsea S. Kidwell, MD Department of Neurology University of Arizona Tucson, AZ 1. Modlinger PS, Wilcox CS, Aslam S. Nitric oxide, oxidative stress, and progression of chronic renal failure. Semin Nephrol. 2004;24:354–365. 2. Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM. The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int. 2002;62:1524–1538. 3. Landmesser U, Dikalov S, Price SR, McCann L, Fukai T, Holland SM, et al. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest. 2003;111:1201–1209. 4. Maffei A, Poulet R, Vecchione C, Colella S, Fratta L, Frati G, et al. Increased basal nitric oxide release despite enhanced free radical production in hypertension. J Hypertens. 2002;20:1135–1142. 5. Taherzadeh Z, Brewster LM, van Montfrans GA, VanBavel E. Function and structure of resistance vessels in black and white people. J Clin Hypertens (Greenwich). 2010;12:431–438.
(Stroke. 2013;44:e232.) © 2013 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.113.003354
Downloaded from http://stroke.ahajournals.org/ at VA MED CTR BOISE on November 15, 2015 e232
Response to Letter Regarding Article, ''Association of Chronic Kidney Disease With Cerebral Microbleeds in Patients With Primary Intracerebral Hemorrhage'' Bruce Ovbiagele and Chelsea S. Kidwell Stroke. 2013;44:e232; originally published online November 5, 2013; doi: 10.1161/STROKEAHA.113.003354 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2013 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/44/12/e232
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
Downloaded from http://stroke.ahajournals.org/ at VA MED CTR BOISE on November 15, 2015
Response to Letter Regarding Article, “Association of Chronic Kidney Disease With Cerebral Microbleeds in Patients With Primary Intracerebral Hemorrhage”
We thank Dr Tsuda for his interest in our recently published article. As he alluded to in his letter, nitrous oxide exerts a powerful influence on the regulation of glomerular filtration rate,1 and mounting evidence suggests that initial renal endothelial damage may lead to superoxide scavenging of nitric oxide, ultimately leading to diffuse severe endothelial dysfunction, including within the cerebrovascular bed.2 However, it must be noted that results from various studies on endogenous nitric oxide conflict, with some studies suggesting a deficiency in nitric oxide with chronic kidney disease,3 and others reporting upregulated nitrous oxide production.4 About the possible interplay of chronic kidney disease, nitric oxide production, and race, reduced nitric oxide bioavailability in the vascular wall may indeed be an important contributor to the observed differences in function and mechanical properties of resistance arteries between blacks and whites,5 but we did not collect data on endothelial function or plasma NO-metabolite levels in the Differences in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) cohort and therefore cannot specifically address this issue directly in the current data set. We share Dr Tsuda’s enthusiasm for future studies aimed at exploring inadequate nitric oxide production as a potential explanation for racial disparities in the influence of chronic kidney disease on vascular brain injury (including cerebral microbleeds).
Disclosures None.
Bruce Ovbiagele, MD, MSc, MAS Department of Neurosciences Medical University of South Carolina Charleston, SC Chelsea S. Kidwell, MD Department of Neurology University of Arizona Tucson, AZ 1. Modlinger PS, Wilcox CS, Aslam S. Nitric oxide, oxidative stress, and progression of chronic renal failure. Semin Nephrol. 2004;24:354–365. 2. Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM. The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int. 2002;62:1524–1538. 3. Landmesser U, Dikalov S, Price SR, McCann L, Fukai T, Holland SM, et al. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest. 2003;111:1201–1209. 4. Maffei A, Poulet R, Vecchione C, Colella S, Fratta L, Frati G, et al. Increased basal nitric oxide release despite enhanced free radical production in hypertension. J Hypertens. 2002;20:1135–1142. 5. Taherzadeh Z, Brewster LM, van Montfrans GA, VanBavel E. Function and structure of resistance vessels in black and white people. J Clin Hypertens (Greenwich). 2010;12:431–438.
(Stroke. 2013;44:e232.) © 2013 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.113.003354
Downloaded from http://stroke.ahajournals.org/ at VA MED CTR BOISE on November 15, 2015 e232
Response to Letter Regarding Article, ''Association of Chronic Kidney Disease With Cerebral Microbleeds in Patients With Primary Intracerebral Hemorrhage'' Bruce Ovbiagele and Chelsea S. Kidwell Stroke. 2013;44:e232; originally published online November 5, 2013; doi: 10.1161/STROKEAHA.113.003354 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2013 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/44/12/e232
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
Downloaded from http://stroke.ahajournals.org/ at VA MED CTR BOISE on November 15, 2015
