This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 25/10/2114    most recent 01.ATV.0000178993.13222.f2v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Kobayashi, N. Articles by Schmid-Schönbein, G. W. Search for Related Content PubMed PubMed Citation Articles by Kobayashi, N. Articles by Schmid-Schönbein, G. W.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2114.)
© 2005 American Heart Association, Inc.

Vascular Biology

Oxidative Stress Promotes Endothelial Cell Apoptosis and Loss of Microvessels in the Spontaneously Hypertensive Rats

Nobuhiko Kobayashi; Frank A. DeLano; Geert W. Schmid-Schönbein

From the Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, Calif.

Correspondence to Dr Geert W. Schmid-Schönbein, Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412. E-mail gwss{at}bioeng.ucsd.edu

Objective— Endothelial cell apoptosis caused by oxidative stress may lead to the loss of microvessels (rarefaction) in hypertension. We examine here the effects of antioxidants on cell apoptosis and rarefaction.

Methods and Results— The juvenile spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were treated with superoxide scavengers, Tempol or Tiron, during growth. After the treatment, oxidative stress status, endothelial cell apoptosis rate, and microvessel length density in skeletal muscle and mesentery were evaluated in comparison with age-matched controls. Untreated 16-week-old SHR had higher oxidative stress (P<0.01) and cell apoptosis rate (P<0.05) and lower microvessel length density (371±17 mm/mm³ [P<0.01]) compared with age-matched WKY rats (435±15 mm/mm³). In the SHR, but not in WKY rats, systemically applied antioxidants attenuated oxidative stress and cell apoptosis rate (P<0.05 versus untreated controls) and prevented the loss of microvessels (411±15 mm/mm³ for Tempol [P<0.01 versus untreated control] and 399±17 mm/mm³ for Tiron [P<0.05]).

Conclusions— Antioxidant treatment with cell-permeable superoxide scavengers inhibits endothelial cell apoptosis and prevents microvessel rarefaction in the SHR during growth.

Loss of microvessels contributes to the development of hypertensive disease. Antioxidants suppressed endothelial cell apoptosis in microvessels and preserved vessel length density in the spontaneously hypertensive rats. Oxidative stress seems to promote endothelial cell apoptosis and loss of microvessels during the development of hypertension.

Key Words: arterial hypertension • capillary • endothelial cell apoptosis • microvessels • oxidative stress • rarefaction • superoxide

This article has been cited by other articles:

				B. I. Levy, E. L. Schiffrin, J.-J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A.J. Struijker-Boudier Impaired Tissue Perfusion: A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus Circulation, August 26, 2008; 118(9): 968 - 976. [Full Text] [PDF]

				F. A. DeLano and G. W. Schmid-Schonbein Proteinase Activity and Receptor Cleavage: Mechanism for Insulin Resistance in the Spontaneously Hypertensive Rat Hypertension, August 1, 2008; 52(2): 415 - 423. [Abstract] [Full Text] [PDF]

				G. K. Soukhova-O'Hare, R. V. Ortines, Y. Gu, A. D. Nozdrachev, S. D. Prabhu, and D. Gozal Postnatal Intermittent Hypoxia and Developmental Programming of Hypertension in Spontaneously Hypertensive Rats: The Role of Reactive Oxygen Species and L-Ca2+ Channels Hypertension, July 1, 2008; 52(1): 156 - 162. [Abstract] [Full Text] [PDF]

				T. V. Serebrovskaya, E. B. Manukhina, M. L. Smith, H. F. Downey, and R. T. Mallet Intermittent Hypoxia: Cause of or Therapy for Systemic Hypertension? Experimental Biology and Medicine, June 1, 2008; 233(6): 627 - 650. [Abstract] [Full Text] [PDF]

				C. H. Coyle, S. Mendralla, S. Lanasa, and K. N. Kader Endothelial Cell Seeding onto Various Biomaterials Causes Superoxide-induced Cell Death J Biomater Appl, July 1, 2007; 22(1): 55 - 69. [Abstract] [PDF]

				S. J. Miller, L. E. Norton, M. P. Murphy, M. C. Dalsing, and J. L. Unthank The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2523 - H2531. [Abstract] [Full Text] [PDF]

				F. Feihl, L. Liaudet, B. Waeber, and B. I. Levy Hypertension: A Disease of the Microcirculation? Hypertension, December 1, 2006; 48(6): 1012 - 1017. [Full Text] [PDF]

				U. P. Kodavanti, M. C. Schladweiler, A. D. Ledbetter, R. V. Ortuno, M. Suffia, P. Evansky, J. H. Richards, R. H. Jaskot, R. Thomas, E. Karoly, et al. The Spontaneously Hypertensive Rat: An Experimental Model of Sulfur Dioxide-Induced Airways Disease Toxicol. Sci., November 1, 2006; 94(1): 193 - 205. [Abstract] [Full Text] [PDF]

				J. Quadrilatero and J. W. E. Rush Increased DNA fragmentation and altered apoptotic protein levels in skeletal muscle of spontaneously hypertensive rats J Appl Physiol, October 1, 2006; 101(4): 1149 - 1161. [Abstract] [Full Text] [PDF]

				M. Feletou and P. M. Vanhoutte Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture) Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H985 - H1002. [Abstract] [Full Text] [PDF]