Control of oxidative stress in microcirculation of spontaneously hypertensive rats

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 288; no. 2; pp. H805 - H812
• Main Authors: DeLano, F. A, Balete, R, Schmid-Schonbein, G. W
• Format: Journal Article
• Language: English
• Published: United States 01.02.2005
• Subjects: Adrenal Cortex - physiology; Adrenalectomy; Animals; Blood Pressure - physiology; Endothelium, Lymphatic - blood supply; Endothelium, Lymphatic - metabolism; Free Radicals - metabolism; Hydralazine - pharmacology; Hypertension - drug therapy; Hypertension - metabolism; Hypertension - physiopathology; Male; Microcirculation - drug effects; Microcirculation - physiology; Nitroblue Tetrazolium; Oxidative Stress - physiology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Splanchnic Circulation - drug effects; Splanchnic Circulation - physiology; Superoxides - metabolism; Vasodilator Agents - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00696.2004

Microcirculation Laboratory, Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, California Submitted 14 July 2004 ; accepted in final form 28 September 2004 One mechanism for organ damage in individuals with arterial hypertension may be due to oxygen free radical production. This study was designed to localize free radicals in a microvascular network of mature spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. Because glucocorticoids play a role in pressure elevation of SHRs, we investigated their role in microvascular free radical formation. Oxygen radical production in mesentery was detected by tetranitroblue tetrazolium reduction to formazan aided by digital light-absorption measurements. Formazan deposits were observed in the endothelial cells and lumens of all microvessels and in lymphatic endothelia but were fewer in tissue parenchyma. The formazan distribution in younger (14–16 wk old) WKY rats and SHRs was heterogeneous with low values in capillaries and small arterioles/venules (<30 µm) but enhanced deposits in larger venules. Adrenalectomy served to reduce the formazan density in SHRs to the level of WKY rats, whereas dexamethasone supplementation of the adrenalectomized rats caused elevation in the larger venules of SHRs. In older (40 wk old) SHRs, formazan levels were elevated in all hierarchies of microvessels. After pressure reduction was employed with chronic hydralazine treatment, the formazan deposits were reduced in all locations of the microcirculation in both WKY rats and SHRs. Elevated formazan deposits were also found in lymphatic endothelium. These results suggest that oxygen free radical production is elevated in both high- and low-pressure regions of SHR microcirculation via a process that is controlled by glucocorticoids. Older SHRs have higher formazan levels than younger SHRs in all microvessels. Chronic hydralazine treatment, which serves to reduce arterial blood pressure, attenuates tetranitroblue tetrazolium reduction in WKY rats and SHRs even in venules of the microcirculation, which has no micropressure elevation. Free radical production may be a more global condition in SHRs and may not be limited to arteries and arterioles. mesentery; arteriole; capillary; venule; superoxide; nitroblue tetrazolium; dexamethasone; Wistar-Kyoto; adrenalectomy; hydralazine Address for reprint requests and other correspondence: G. W. Schmid-Schönbein, Dept. of Bioengineering, Whitaker Institute for Biomedical Engineering, Univ. of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0412 (E-mail: gwss{at}bioeng.ucsd.edu )