Elevation of oxidative stress in the aorta of genetically hypertensive mice Mukarram Uddin a,1 , Hong Yang a,1 , MingJian Shi a , Manorama Polley-Mandal a , ZhongMao Guo a,b, * a Department of Anatomy and Physiology, School of Medicine, Meharry Medical College, 1005 Dr. D.B. Todd Jr. Blvd., Nashville, TN 37208, USA b Department of Internal Medicine, Meharry Medical College, Nashville, TN 37208, USA Received 4 December 2002; received in revised form 5 March 2003; accepted 14 April 2003 Abstract Hypertension is an age-dependent disorder. Oxidative stress has been suggested to play a role in aging and age-dependent disorders. The objective of this study is to examine the oxidant and antioxidant status in the aorta of a mouse model with high blood pressure (BPH). Our results showed that the level of malondialdehyde (MDA) in the aorta of BPH mice was approximately 2.6-fold higher than that of the normal blood pressure (BPN) mice, suggesting an increased in vivo oxidative stress in the arterial wall of BPH mice. In addition, the release of hydrogen peroxide (H 2 O 2 ) from the aorta of BPH mice was significantly faster than that of BPN mice. To determine if the increased H 2 O 2 release is related to a down-regulation of antioxidant enzymes in the arterial wall, we measured the activities of the major antioxidant enzymes in mouse aortas. We observed that the activities of Cu/Zn-superoxide dismutase (SOD) and glutathione peroxidase-1 in BPH mice were similar to BPN mice. On the other hand, the catalase activity in the aorta of BPH mice was significantly reduced while the activities of Mn-SOD and extracellular (EC)-SOD in the aorta of BPH mice were significantly elevated as compared with BPN mice. These results suggest that increase in SOD activity and decrease in catalase activity might be responsible for the increased release of H 2 O 2 in the arterial wall of BPH mice. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Hypertensive mice; Oxidative stress; Antioxidant enzymes 1. Introduction Age-related increase in blood pressure has been considered to be a component of the aging process (Schlager, 1981). Oxidative stress has been suggested to play a role in the aging process. If the pathogenesis of hypertension involves the mechanism of the aging process, one would expect that hypertension is asso- ciated with an increased oxidative stress. Over the past decade a number of investigators have tested this hypothesis, and there is mounting evidence to support the role of oxidative stress in hypertension. For example, clinical studies have shown that the level of lipid peroxides in the plasma of hypertensive patients is significantly higher than that of normotensive subjects (Koska et al., 1999; Kumar and Das, 2000). In addition, hypertensive patients have shown increased plasma hydrogen peroxide (H 2 O 2 )(Lacy et al., 2000). More- over, the ability of blood cells to produce reactive oxygen species (ROS), e.g. superoxide (O 2 + ) and H 2 O 2 , is enhanced in hypertensive patients (Kristal et al., 1998). Oxidative stress also has been implicated in a variety of hypertensive animal models. For example, increase in lipid peroxidation in the plasma and increase in ROS generation in vascular cells have been found in spontaneously hypertensive rats (SHR) (Newaz and Nawal, 1999) and rats with lead-induced hypertension (Vaziri et al., 1997), mineralocorticoid-induced hyper- tension (Beswick et al., 2001), salt-sensitive hypertension (Swei et al., 1997) and obesity-induced hypertension (Dobrian et al., 2001). Thus, oxidative stress appears to be a common feature of hypertensive disorders from diverse origins. * Corresponding author. Tel.:  /1-615-327-6288; fax:  /1-615-327- 6655. E-mail address: zguo@mmc.edu (Z. Guo). 1 Contributed equally to this work. Mechanisms of Ageing and Development 124 (2003) 811  /817 www.elsevier.com/locate/mechagedev 0047-6374/03/$ - see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0047-6374(03)00135-0