Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension.

BACKGROUND The major source of superoxide (.O2-) in vascular tissues is an NADH/NADPH-dependent, membrane-bound oxidase. We have previously shown that this oxidase is activated in angiotensin II-but not norepinephrine-induced hypertension. We hypothesized that hypertension associated with chronically elevated angiotensin II might be caused in part by vascular .O2- production. METHODS AND RESULTS We produced hypertension in rats by a 5-day infusion of angiotensin II or norepinephrine. Rats were also treated with liposome-encapsulated superoxide dismutase (SOD) or empty liposomes. Arterial pressure was measured in conscious rats under baseline conditions and during bolus injections of either acetylcholine or nitroprusside. Vascular .O2- production was assessed by lucigenin chemiluminescence. In vitro vascular relaxations were examined in organ chambers. Norepinephrine infusion increased blood pressure to a similar extent as angiotensin II infusion (179 +/- 5 and 189 +/- 4 mm Hg, respectively). In contrast, angiotensin II-induced hypertension was associated with increased vascular .O2- production, whereas norepinephrine-induced hypertension was not. Treatment with liposome-encapsulated SOD reduced blood pressure by 50 mm Hg in angiotensin II-infused rats while having no effect on blood pressure in control rats or rats with norepinephrine-induced hypertension. Similarly, liposome-encapsulated SOD enhanced in vivo hypotensive responses to acetylcholine and in vitro responses to endothelium-dependent vasodilators in angiotensin II-treated rats. CONCLUSIONS Hypertension caused by chronically elevated angiotensin II is mediated in part by .O2-, likely via degradation of endothelium-derived NO. Increased vascular .O2- may contribute to vascular disease in high renin/angiotensin II states.

[1]  M. Wilson,et al.  The simultaneous generation of superoxide and nitric oxide can initiate lipid peroxidation in human low density lipoprotein. , 1992, Free radical research communications.

[2]  L. Ignarro,et al.  Formation of free nitric oxide from l-arginine by nitric oxide synthase: direct enhancement of generation by superoxide dismutase. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[3]  M. Tarpey,et al.  Peroxynitrite stimulates vascular smooth muscle cell cyclic GMP synthesis , 1995, FEBS letters.

[4]  H. Fuder,et al.  Alpha-adrenoceptor mediated facilitation of acetylcholine release in the rat perfused heart. , 1990, The Journal of pharmacology and experimental therapeutics.

[5]  F. Abboud,et al.  Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine. , 1995, Circulation research.

[6]  J. Crapo,et al.  Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase. , 1984, The Journal of clinical investigation.

[7]  H. Sies,et al.  Reversible conversion of nitroxyl anion to nitric oxide by superoxide dismutase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[8]  K. Pritchard,et al.  Involvement of nitric oxide and nitrosothiols in relaxation of pulmonary arteries to peroxynitrite. , 1994, The American journal of physiology.

[9]  I. Fridovich,et al.  Superoxide radical and superoxide dismutases: threat and defense. , 1980, Acta physiologica Scandinavica. Supplementum.

[10]  H. Poulsen,et al.  Nitrate tolerance impairs nitric oxide-mediated vasodilation in vivo. , 1996, Cardiovascular research.

[11]  D. Harrison,et al.  Hypercholesterolemia increases endothelial superoxide anion production. , 1993, The Journal of clinical investigation.

[12]  D. Harrison,et al.  Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. , 1996, The Journal of clinical investigation.

[13]  W. A. Bradley,et al.  Superoxide and peroxynitrite in atherosclerosis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[14]  T. Resink,et al.  Stimulation of endothelin mRNA and secretion in rat vascular smooth muscle cells: a novel autocrine function. , 1990, Cell regulation.

[15]  G. Natoli,et al.  Reactive Oxygen Intermediates Mediate Angiotensin II-induced c-Jun•c-Fos Heterodimer DNA Binding Activity and Proliferative Hypertrophic Responses in Myogenic Cells (*) , 1995, The Journal of Biological Chemistry.

[16]  G. Rao,et al.  Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. , 1992, Circulation research.

[17]  I. Fridovich,et al.  Superoxide radical and superoxide dismutases. , 1995, Annual review of biochemistry.

[18]  J. Crapo,et al.  Liposome-mediated augmentation of superoxide dismutase in endothelial cells prevents oxygen injury. , 1983, The Journal of biological chemistry.

[19]  R W Alexander,et al.  Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. , 1994, Circulation research.

[20]  P. Kaminski,et al.  NADH oxidoreductase is a major source of superoxide anion in bovine coronary artery endothelium. , 1994, The American journal of physiology.

[21]  H. van Goor,et al.  Immunohistochemical antigen demonstration in plastic-embedded lymphoid tissue. , 1988, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[22]  T. Cruz,et al.  Involvement of Reactive Oxygen Species in Cytokine and Growth Factor Induction of c-fos Expression in Chondrocytes(*) , 1995, The Journal of Biological Chemistry.

[23]  B. Berk,et al.  Angiotensin II-stimulated protein synthesis in cultured vascular smooth muscle cells. , 1989, Hypertension.

[24]  Joseph Loscalzo,et al.  A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds , 1993, Nature.

[25]  J. Beckman Peroxynitrite versus Hydroxyl Radical: The Role of Nitric Oxide in Superoxide‐Dependent Cerebral Injury a , 1994, Annals of the New York Academy of Sciences.

[26]  R. Alexander,et al.  Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. , 1993, The Journal of clinical investigation.

[27]  P. Gallop,et al.  An NADPH oxidase superoxide-generating system in the rabbit aorta. , 1995, The American journal of physiology.

[28]  J. Beckman,et al.  Peroxynitrite, a product of superoxide and nitric oxide, produces coronary vasorelaxation in dogs. , 1994, The Journal of pharmacology and experimental therapeutics.

[29]  J. Laragh,et al.  Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension. , 1991, The New England journal of medicine.

[30]  V. Sukhatme,et al.  Induction of immediate-early genes by angiotensin II and endothelin-1 in adult rat cardiomyocytes , 1993, Journal of hypertension.

[31]  S. Tanganelli,et al.  α1Adrenoreceptpr‐Mediated Increase in Acetylcholine Release in Braip Slices During Morphine Tolerance , 1989, Journal of neurochemistry.

[32]  B. Freeman,et al.  Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. , 1991, Archives of biochemistry and biophysics.

[33]  B. Freeman,et al.  Detection of superoxide generated by endothelial cells. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[34]  A. Kraft,et al.  Induction of the proto-oncogene c-jun by angiotensin II , 1990, Molecular and cellular biology.

[35]  D. Harrison,et al.  Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance. , 1995, The Journal of clinical investigation.

[36]  Z. Katušić,et al.  Superoxide anion is an endothelium-derived contracting factor. , 1989, The American journal of physiology.

[37]  D. Harrison,et al.  Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. , 1991, Circulation research.

[38]  T. Matsubara,et al.  Superoxide anion release by human endothelial cells: Synergism between a phorbol ester and a calcium ionophore , 1986, Journal of cellular physiology.

[39]  M. Wolin,et al.  Sites of superoxide anion production detected by lucigenin in calf pulmonary artery smooth muscle. , 1994, The American journal of physiology.

[40]  B. Freeman,et al.  Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[41]  J. Sasaki,et al.  Does superoxide underlie the pathogenesis of hypertension? , 1991, Proceedings of the National Academy of Sciences of the United States of America.