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(Hypertension. 1995;25:1083-1089.)
© 1995 American Heart Association, Inc.
Articles |
In Vivo Evidence for Microvascular Oxidative Stress in Spontaneously Hypertensive Rats
Hydroethidine Microfluorography
From the Institute for Biomedical Engineering, University of California at San Diego, La Jolla.
Correspondence to Dr Geert W. Schmid-Schönbein, Institute for Biomedical Engineering and Department of Bioengineering, University of California at San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0412.
Abstract The factors that predispose to the accelerated organ injury that accompanies the hypertensive syndrome have remained speculative and without a firm experimental basis. Indirect evidence has suggested that a key feature may be related to an enhanced oxygen radical production. The purpose of this study was to refine and use a technique to visualize evidence of spontaneous microvascular oxidative stress in vivo in the spontaneously hypertensive rat (SHR) compared with its normotensive control, the Wistar-Kyoto rat (WKY). We investigated the effects of adrenal glucocorticoids on the microvascular oxidative stress sequence. The mesentery was superfused with hydroethidine, a reduced, nonfluorescent precursor of ethidium bromide. In the presence of oxidative challenge, hydroethidine is transformed intracellularly into the fluorescent compound ethidium bromide, which binds to DNA and can be detected by virtue of its red fluorescence. The fluorescent light emission from freshly exteriorized and otherwise unstimulated mesentery microvessels was recorded by digital microscopy. The number of ethidium bromide–positive nuclei along the arteriolar and venular walls in SHR was found to be significantly increased above the level exhibited by WKY. The elevation in ethidium bromide fluorescence in SHR arterioles could be attenuated by a synthetic glucocorticoid inhibitor and in rats subjected to adrenalectomy. The administration of glucocorticoids after adrenalectomy by injection of dexamethasone restored the oxidative reaction in SHR arterioles. Treatment with dimethylthiourea and with a xanthine oxidase inhibitor attenuated the superoxide formation. Although a nitric oxide synthase inhibitor (NG-nitro-L-arginine methyl ester) enhanced the ethidium bromide staining in WKY, it did not affect that in SHR. Our findings suggest an enhancement of spontaneous oxidative stress in the microvascular wall of SHR that appears to be associated with glucocorticoid synthesis.
Key Words: free radicals • arterioles • adrenalectomy • glucocorticoids
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H. Suzuki, F. A. Delano, N. Jamshidi, D. Katz, M. Mori, K. Kosaki, R. A. Gottlieb, H. Ishii, and G. W. Schmid-Schonbein Enhanced DNA fragmentation in the thymus of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H2135 - H2140. [Abstract] [Full Text] [PDF]
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J. R. Kersten and D. C. Warltier Modulation of the adaptive response to myocardial ischemia by coexisting disease Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H2268 - H2270. [Full Text] [PDF]
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C. G. Schnackenberg and C. S. Wilcox Two-Week Administration of Tempol Attenuates Both Hypertension and Renal Excretion of 8-Iso Prostaglandin F2{alpha} Hypertension, January 1, 1999; 33(1): 424 - 428. [Abstract] [Full Text] [PDF]
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T. Marumo, V. B. Schini-Kerth, R. P. Brandes, and R. Busse Glucocorticoids Inhibit Superoxide Anion Production and p22 Phox mRNA Expression in Human Aortic Smooth Muscle Cells Hypertension, December 1, 1998; 32(6): 1083 - 1088. [Abstract] [Full Text] [PDF]
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A. Huang, D. Sun, G. Kaley, and A. Koller Superoxide Released to High Intra-arteriolar Pressure Reduces Nitric Oxide–Mediated Shear Stress– and Agonist-Induced Dilations Circ. Res., November 2, 1998; 83(9): 960 - 965. [Abstract] [Full Text] [PDF]
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J. Laakso, E. Mervaala, J.-J. Himberg, T.-L. Teravainen, H. Karppanen, H. Vapaatalo, and R. Lapatto Increased Kidney Xanthine Oxidoreductase Activity in Salt-Induced Experimental Hypertension Hypertension, November 1, 1998; 32(5): 902 - 906. [Abstract] [Full Text] [PDF]
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C. G. Schnackenberg, W. J. Welch, and C. S. Wilcox Normalization of Blood Pressure and Renal Vascular Resistance in SHR With a Membrane-Permeable Superoxide Dismutase Mimetic : Role of Nitric Oxide Hypertension, July 1, 1998; 32(1): 59 - 64. [Abstract] [Full Text] [PDF]
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F. J. Miller, D. D. Gutterman, C. D. Rios, D. D. Heistad, and B. L. Davidson Superoxide Production in Vascular Smooth Muscle Contributes to Oxidative Stress and Impaired Relaxation in Atherosclerosis Circ. Res., June 29, 1998; 82(12): 1298 - 1305. [Abstract] [Full Text] [PDF]
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P. S. Tsao, J. Niebauer, R. Buitrago, P. S. Lin, B.-y. Wang, J. P. Cooke, Y-d. Ida Chen, and G. M. Reaven Interaction of Diabetes and Hypertension on Determinants of Endothelial Adhesiveness Arterioscler Thromb Vasc Biol, June 1, 1998; 18(6): 947 - 953. [Abstract] [Full Text] [PDF]
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H. Suzuki, F. A. DeLano, D. A. Parks, N. Jamshidi, D. N. Granger, H. Ishii, M. Suematsu, B. W. Zweifach, and G. W. Schmid-Schonbein Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats PNAS, April 14, 1998; 95(8): 4754 - 4759. [Abstract] [Full Text] [PDF]
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T.-C. Chou, M.-H. Yen, C.-Y. Li, and Y.-A. Ding Alterations of Nitric Oxide Synthase Expression With Aging and Hypertension in Rats Hypertension, February 1, 1998; 31(2): 643 - 648. [Abstract] [Full Text] [PDF]
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M. A. W. Broeders, G.-J. Tangelder, D. W. Slaaf, R. S. Reneman, and M. G. A. oude Egbrink Endogenous Nitric Oxide Protects Against Thromboembolism in Venules But Not in Arterioles Arterioscler Thromb Vasc Biol, January 1, 1998; 18(1): 139 - 145. [Abstract] [Full Text] [PDF]
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A. Swei, F. Lacy, F. A. DeLano, and G. W. Schmid-Schonbein Oxidative Stress in the Dahl Hypertensive Rat Hypertension, December 1, 1997; 30(6): 1628 - 1633. [Abstract] [Full Text]
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A. Huang and A. Koller Endothelin and Prostaglandin H2 Enhance Arteriolar Myogenic Tone in Hypertension Hypertension, November 1, 1997; 30(5): 1210 - 1215. [Abstract] [Full Text]
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H. Suzuki, B. W. Zweifach, and G. W. Schmid-Schonbein Vasodilator Response of Mesenteric Arterioles to Histamine in Spontaneously Hypertensive Rats Hypertension, September 1, 1995; 26(3): 397 - 400. [Abstract] [Full Text]
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 S. Lopez-Ongil, V. Senchak, M. Saura, C. Zaragoza, M. Ames, B. Ballermann, M. Rodriguez-Puyol, D. Rodriguez-Puyol, and C. J. Lowenstein Superoxide Regulation of Endothelin-converting Enzyme J. Biol. Chem., August 18, 2000; 275(34): 26423 - 26427. [Abstract] [Full Text] [PDF]
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B. Rodriguez-Iturbe, Y. Quiroz, M. Nava, L. Bonet, M. Chavez, J. Herrera-Acosta, R. J. Johnson, and H. A. Pons Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats Am J Physiol Renal Physiol, February 1, 2002; 282(2): F191 - F201. [Abstract] [Full Text] [PDF]
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M. A.W. Broeders, G. J. Tangelder, D. W. Slaaf, R. S. Reneman, and M. G.A. oude Egbrink Hypercholesterolemia Enhances Thromboembolism in Arterioles but Not Venules: Complete Reversal by L-Arginine Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 680 - 685. [Abstract] [Full Text] [PDF]
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