Enhanced superoxide anion formation in vascular tissues from spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats

Wu, Rong; Millette, Esther; Wu, Lin‐Sheng; Champlain, Jacques de

doi:10.1097/00004872-200104000-00011

Cited by 170 publications

(131 citation statements)

References 37 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…Similarly, in recent studies from our laboratory, it was reported that the enhanced O 2 Ϫ formation in aortic tissue resulted mainly from an increased NADH oxidase activity in SHR and deoxycorticosterone acetate-salt hypertensive rats. 26 In addition, the present study suggests an involvement of the vascular oxidative stress in the elevation of systolic arterial pressure induced by chronic glucose intake, because a significant positive relationship was observed between aortic O 2 Ϫ production and systolic blood pressure. A causal relationship between those parameters still remains to be clarified.…”

Section: Discussionsupporting

confidence: 56%

Prevention of Hypertension, Insulin Resistance, and Oxidative Stress by α-Lipoic Acid

2002

Self Cite

View full text Add to dashboard Cite

Abstract-The aim of the present study was to investigate whether a dietary supplementation of ␣-lipoic acid could prevent blood pressure elevation, insulin resistance, and the increase in aorta superoxide anion production in a new experimental model of hypertension associated with insulin resistance. Sprague-Dawley rats were given 10% D-glucose in their drinking water combined either with a normal chow diet or with an ␣-lipoic acid-supplemented diet and were compared with control rats during 3 weeks. Oxidative stress was evaluated by measuring the aortic superoxide anion production using the lucigenin chemiluminescence method. Increases in blood pressure, insulin resistance, and aorta superoxide production observed in glucose-fed rats were prevented by the supplementation of the diet with lipoic acid. Positive correlations were found between aortic superoxide production and blood pressure, between insulin resistance and blood pressure, or between superoxide production and insulin resistance. Moreover, a decrease in the activity of plasma glutathione peroxidase observed in the glucose-fed rats was prevented by lipoic acid treatment. These findings demonstrate that high-glucose feeding rapidly induced hypertension and insulin resistance in association with the induction of a vascular oxidative stress. The antihypertensive action and the prevention of insulin resistance by lipoic acid appears to be associated to its antioxidative properties because it prevented the increase in oxidative stress, as reflected by the normalization of superoxide anion production in aorta and the prevention of the fall in the activity of glutathione peroxidase in the glucose-fed rats. (Hypertension. 2002;39:303-307.)

show abstract

Section: Discussionsupporting

confidence: 56%

Prevention of Hypertension, Insulin Resistance, and Oxidative Stress by α-Lipoic Acid

2002

Self Cite

View full text Add to dashboard Cite

show abstract

“…Increased ROS levels have been linked to hypertension in rat models such as spontaneously hypertensive rats, deoxycorticosterone acetate-salt hypertensive rats, Dahl salt-sensitive rats, ANG II-induced hypertensive rats, and renovascular hypertensive rats (22,35,41,46,47). Several studies have examined the contractile response of arteries to ROS.…”

Section: Discussionmentioning

confidence: 99%

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Jin

Zhao

Webb

2004

American Journal of Physiology-Heart and Circulatory Physiology

225

185

View full text Add to dashboard Cite

. Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta. Am J Physiol Heart Circ Physiol 287: H1495-H1500; 2004; 10.1152/ajpheart.01006.2003.-Evidence indicates that both the Rho/ Rho kinase signaling pathway and reactive oxygen species (ROS) such as superoxide and H 2O2 are involved in the pathogenesis of hypertension. This study aimed to determine whether ROS-induced vascular contraction is mediated through activation of Rho/Rho kinase. Rat aortic rings (endothelium denuded) were isolated and placed in organ chambers for measurement of isometric force development. ROS were generated by a xanthine (X)-xanthine oxidase (XO) mixture. The antioxidants tempol (3 mM) and catalase (1,200 U/ml) or the XO inhibitor allopurinol (400 M) significantly reduced X/XOinduced contraction. A Rho kinase inhibitor, (ϩ)-(R)-trans-4-(1-aminoethyl-N-4-pyridil)cyclohexanecarboxamide dihydrochloride (Y-27632), decreased the contraction in a concentration-dependent manner; however, the Ca 2ϩ -independent protein kinase C inhibitor rottlerin did not have an effect on X/XO-induced contraction. Phosphorylation of the myosin light chain phosphatase target subunit (MYPT1) was increased by ROS, and preincubation with Y-27632 blocked this increased phosphorylation. Western blotting for cytosolic and membrane-bound fractions of Rho showed that Rho was increased in the membrane fraction by ROS, suggesting activation of Rho. These observations demonstrate that ROS-induced Ca 2ϩ sensitization is through activation of Rho and a subsequent increase in Rho kinase activity but not Ca 2ϩ -independent PKC. myosin light chain phosphatase; smooth muscle contraction; antioxidants CONTRACTION OF SMOOTH MUSCLE is regulated by both Ca 2ϩ -dependent and Ca 2ϩ -independent (Ca 2ϩ sensitization) mechanisms. A rise in intracellular Ca 2ϩ levels leads to myosin light chain (MLC) kinase activation, resulting in an increase in MLC phosphorylation. Importantly, MLC phosphorylation can also be increased through inhibition of MLC phosphatase, which augments smooth muscle force generation without a change in intracellular Ca 2ϩ (38).In recent years, studies have revealed that the small GTPase Rho and its downstream target Rho kinase mediate the Ca 2ϩ sensitization of smooth muscle contraction (37). The exchange of bound GDP for GTP activates Rho and stimulates its translocation from cytosol to membrane. Rho-GTP phosphorylates Rho kinase, which inhibits MLC phosphatase activity by phosphorylation of the MLC phosphatase target subunit (MYPT1). A decrease in MLC phosphatase activity increases phosphorylation of myosin and therefore contributes to smooth muscle contraction at low levels of intracellular Ca 2ϩ concentration. Strong evidence suggests that increased Rho/Rho kinase-dependent Ca 2ϩ sensitization contributes to hypertension and inhibition of Rho or Rho kinase reduces blood pressure (33, 42). Some heterotrimetric G protein-coupled receptor (GPCR) agonists, including angiotensin II (ANG II) and endothelin (ET)-1, induce smooth mus...

show abstract

“…9,10 Thus, the renin-angiotensin system seems to play an important role in regulating vascular VCAM-1 expression via superoxide production. Recently, it has been reported that there is a remarkably high level of superoxide in the aortas of DOCA-salt hypertensive rats, 14,15 a model characterized by its depressed plasma renin activity. 16 These latter studies suggest that Ang II is not a sole stimulus of superoxide and raise the possibility that the increased superoxide in DOCA-salt hypertension may contribute to vascular adhesion molecule expression, such as VCAM-1.…”

Section: Discussionmentioning

confidence: 99%

“…11 The elevated superoxide is present throughout the atherosclerotic vessel wall, 12 and a major source of superoxide is from the electron transport chain in mitochondrial respiration. 13 Two recent studies have indicated that there is also a substantial increase of vascular superoxide with reduced NO release in deoxycorticosterone acetate (DOCA)-salt hypertension, 14,15 a model well known for its suppressed plasma renin and angiotensin levels. 16 However, the level of vascular VCAM-1 expression has never been investigated in this model of hypertension.…”

mentioning

confidence: 99%

Gene Transfer of Endothelial NO Synthase and Manganese Superoxide Dismutase on Arterial Vascular Cell Adhesion Molecule-1 Expression and Superoxide Production in Deoxycorticosterone Acetate-Salt Hypertension

Crockett

Wang

et al. 2002

ATVB

View full text Add to dashboard Cite

Abstract-Enhanced vascular cell adhesion molecule-1 (VCAM-1) expression directly contributes to vascular dysfunction in hypertension. Decreased NO and/or increased superoxide are causative factors for such an event in the vessel wall. The present study was undertaken to determine whether gene transfer of endothelial NO synthase (eNOS) or manganese superoxide dismutase (MnSOD) affects VCAM-1 levels in arteries from hypertensive rats. Isolated carotid and femoral arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats were transduced for 4 hours with adenoviral vectors encoding eNOS, MnSOD, or ␤-galactosidase reporter genes. Recombinant eNOS or MnSOD expression was evident morphologically and quantitatively 24 hours after gene transfer. Immunohistochemistry, ELISA, and Western blot techniques were used to determine VCAM-1 expression and levels. In addition, endogenous eNOS and MnSOD and in situ superoxide levels were analyzed by immunoblotting and fluorescence confocal microscopy, respectively. Arterial VCAM-1 expression was significantly higher in DOCA-salt hypertensive rats than in sham-operated rats; this expression was accompanied by decreased MnSOD but unaltered endogenous eNOS levels. VCAM-1 expression was significantly lower in MnSOD-and eNOS-transduced hypertensive arteries, with a concomitant reduction of superoxide level. These results suggest that gene transfer of MnSOD or eNOS suppresses arterial VCAM-1 expression in DOCA-salt hypertension by reducing the superoxide level. A lthough hypertension is one of the key risk factors for atherosclerosis, the underlying molecular and cellular mechanisms remain to be delineated. 1 Enhanced adhesion molecule expression is known to contribute directly to vascular dysfunction in hypertension. 2 Vascular cell adhesion molecule-1 (VCAM-1) is an early marker of endothelial activation and dysfunction, leukocyte infiltration, and vascular remodeling in the development of early atherosclerotic lesions (fatty streaks and fibrous plaques). 2-5 Although VCAM-1 is structurally similar to intercellular adhesion molecule-1 and other adhesion molecules, its pattern of expression is unique. It exhibits low to negligible expression under baseline conditions but is profoundly upregulated by proatherosclerotic conditions in animal models and in humans. [2][3][4][5] In addition, compared with other adhesion molecules whose expression often extends into uninvolved and/or lesion-protected regions of the vessel wall, VCAM-1 expression is largely restricted to atherosclerotic lesions and lesionpredisposed regions. 2-5 Consistent with these phenomena, a recent study has demonstrated that VCAM-1, but not intercellular adhesion molecule-1 (ICAM-1), plays a critical role in early atherogenesis. 6 Enhanced adhesion molecule expression has been ascribed to an imbalance between oxidative stress and antioxidant activity. Experimental evidence suggests that NO and superoxide are 2 key regulating factors for the expression of adhesion molecules, including VCAM-1. 7,8 In angiotensi...

show abstract

Enhanced superoxide anion formation in vascular tissues from spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats

Cited by 170 publications

References 37 publications

Prevention of Hypertension, Insulin Resistance, and Oxidative Stress by α-Lipoic Acid

Prevention of Hypertension, Insulin Resistance, and Oxidative Stress by α-Lipoic Acid

Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta

Gene Transfer of Endothelial NO Synthase and Manganese Superoxide Dismutase on Arterial Vascular Cell Adhesion Molecule-1 Expression and Superoxide Production in Deoxycorticosterone Acetate-Salt Hypertension

Contact Info

Product

Resources

About