Angiotensin II Type 1 Receptor Antagonist and Angiotensin-Converting Enzyme Inhibitor Altered the Activation of Cu/Zn-Containing Superoxide Dismutase in the Heart of Stroke-Prone Spontaneously Hypertensive Rats

Tanaka, Masakazu; Umemoto, Seiji; Kawahara, Shinji; Kubo, Makoto; Itoh, Shinichi; Umeji, Kyoko; Matsuzaki, Masunori

doi:10.1291/hypres.28.67

Cited by 42 publications

(32 citation statements)

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“…This hypothesis is supported by recent experiments performed using the vascular tissue of stroke-prone SHR (44,45), in which the inhibition of angiotensin receptors or the angiotensin-converting enzyme system reduced ROS production. Our results are also consistent with investigations showing that cardioprotective treatments are mediated by a restoration or up-regulation of antioxidant enzymes (42,45). It is recognized that an increase in collagen concentration is an integral part of the extracellular matrix remodeling that takes place in the LVs during the natural aging process (66) and as well as in response to a variety of pathologies resulting in hypertrophy of this chamber (67,68).…”

Section: Discussionmentioning

confidence: 60%

“…Another explanation for the observed differences would be related to angiotensin II content, which appears to be involved in the genesis of oxidative stress in tissues other than cardiac tissue in SHR (65). This hypothesis is supported by recent experiments performed using the vascular tissue of stroke-prone SHR (44,45), in which the inhibition of angiotensin receptors or the angiotensin-converting enzyme system reduced ROS production. Our results are also consistent with investigations showing that cardioprotective treatments are mediated by a restoration or up-regulation of antioxidant enzymes (42,45).…”

Section: Discussionmentioning

confidence: 85%

“…The fact that hypertension improves with antioxidant therapy implies that oxidative stress is involved in that pathology (41). Recent investigations using hypertensive models other than SHR have shown that a decrease in oxidative stress is one of the mechanisms responsible for the efficacy of anti- hypertensive treatments such as calcium antagonists (42,43), angiotensin II type 1 receptor antagonists, or angiotensin-converting enzyme inhibitors (44,45).…”

Section: Discussionmentioning

confidence: 99%

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Is Cardiac Hypertrophy in Spontaneously Hypertensive Rats the Cause or the Consequence of Oxidative Stress?

et al. 2008

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The aim of this work was to assess the possible correlation between oxidative damage and the development of cardiac hypertrophy in heart tissue from young (40-d-old) and older (4-, 11-and 19-month-old) spontaneously hypertensive rats (SHR) in comparison with age-matched Wistar (W) rats. To this end, levels of thiobarbituric acid reactive substances (TBARS), nitrotyrosine contents, NAD(P)H oxidase activity, superoxide production, and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were determined. Compared to age-matched normotensive rats, SHR showed a significant increase in systolic blood pressure from 40 d of age and left ventricular hypertrophy (LVH) was significantly evident from 4 months of age. W rats (11-and 19-month-old) also showed an increase in LVH with aging. TBARS and nitrotyrosine levels were similar in young rats from both strains and were significantly increased with age in both strains, with the values in SHR being significantly higher than those in age-matched W rats. NAD(P)H activity was similar in young SHR and W rats, whereas it was higher in aged SHR compared with age-matched W rats. Compared to W rats, superoxide production was higher in aged SHR, and was abolished by NAD(P)H inhibition with apocynin. CAT activity was increased in the hearts of 4-month-old SHR compared to age-matched W rats and was decreased in the hearts of the oldest SHR compared to the oldest W rats. SOD and GPx activities decreased in both rat strains with aging. Moreover, an increase in collagen deposition with aging was evident in both rat strains. Taken together, these data showed that aged SHR exhibited higher cardiac hypertrophy and oxidative damage compared to W rats, indicating that the two undesirable effects are associated. That is, oxidative stress appears to be a cause and/or consequence of hypertrophy development in this animal model. (Hypertens Res 2008; 31: 1465-1476)

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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Is Cardiac Hypertrophy in Spontaneously Hypertensive Rats the Cause or the Consequence of Oxidative Stress?

et al. 2008

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“…8,18,19 A luminescence assay was performed in a balanced salt solution buffer containing 5 mol/L of lucigenin (Sigma) using a luminescence reader (Berthold Technology). The reaction was started by adding 100 mol/L of ␤-NAD(P)H (Sigma) as the substrate.…”

Section: Nad(p)h-dependent Superoxide Productionmentioning

confidence: 99%

Inhibition of Rac1-Derived Reactive Oxygen Species in Nucleus Tractus Solitarius Decreases Blood Pressure and Heart Rate in Stroke-Prone Spontaneously Hypertensive Rats

et al. 2007

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Abstract-Reactive oxygen species (ROS) in the brain are thought to contribute to the neuropathogenesis of hypertension by enhancing sympathetic nervous system activity. The nucleus tractus solitarius (NTS), which receives afferent input from baroreceptors, has an important role in cardiovascular regulation. reduced nicotinamide-adenine dinucleotide phosphate oxidase is thought to be a major source of ROS in the NTS. Rac1 is a small G protein and a key component of reduced nicotinamide-adenine dinucleotide phosphate oxidase. The role of Rac1-derived ROS in the NTS in cardiovascular regulation of hypertension is unknown. Therefore, we examined whether inhibition of Rac1 in the NTS decreases ROS generation, thereby reducing blood pressure in stroke-prone spontaneously hypertensive rats (SHRSPs).The basal Rac1 activity level in the NTS was greater in SHRSPs than in Wistar-Kyoto rats. Inhibition of Rac1, induced by transfecting adenovirus vectors encoding dominant-negative Rac1 into the NTS, decreased blood pressure, heart rate, and urinary norepinephrine excretion in SHRSPs but not in Wistar-Kyoto rats. Inhibition of Rac1 also reduced nicotinamide-adenine dinucleotide phosphate oxidase activity and ROS generation. In addition, Cu/Zn-superoxide dismutase activity in the NTS of SHRSPs was decreased compared with that of Wistar-Kyoto rats, despite the increased ROS generation. Overexpression of Cu/Zn-superoxide dismutase in the NTS decreased blood pressure and heart rate in SHRSPs. These results indicate that the activation of Rac1 in the NTS generates ROS via reduced nicotinamide-adenine dinucleotide phosphate oxidase in SHRSPs, and this mechanism might be important for the neuropathogenesis of hypertension in SHRSPs. Key Words: blood pressure Ⅲ heart rate Ⅲ sympathetic nervous system Ⅲ hypertension Ⅲ brain T here is accumulating evidence that reactive oxygen species (ROS) in the cardiovascular regulatory nuclei in the brain have a crucial role in blood pressure regulation in hypertension via modulating the sympathetic nervous system. 1-5 Reduced nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase is a major source of ROS in hypertension 6 and has a critical role in generating ROS in the brain. 2,5,7 Rac1 is a small G protein that is an important signaling molecule involved in integrating intracellular transduction pathways toward NAD(P)H oxidase activation. 2,8,9 Rac1 requires lipid modifications to migrate from the cytosol to the plasma membrane, which is a necessary step for activating the ROSgenerating NAD(P)H oxidase enzyme system. 8,9 The nucleus tractus solitarius (NTS) in the brain stem has an important role in cardiovascular regulation. 10 -16 The NTS receives afferent input from baroreceptors and chemoreceptors 12 and has reciprocal interconnections with other nuclei involved in central autonomic regulation. 17 In addition, the essential NAD(P)H oxidase subunit gp91 phox is present in somatodendritic and axonal profiles that contain angiotensin II (Ang II) subtype 1 receptors in the NTS, and Ang I...

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“…Results from AT1 immunoprecipitation experiments suggested that this failure was due to uncoupling of AT1 with Gi proteins. The activation of AT1 produces oxidative stress (37,38). The coupling state of signaling proteins can be altered in SHR.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Inward Rectifier K+ Currents by Angiotensin II in Rat Atrial Myocytes: Lack of Effects in Cells from Spontaneously Hypertensive Rats

et al. 2006

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Angiotensin II Type 1 Receptor Antagonist and Angiotensin-Converting Enzyme Inhibitor Altered the Activation of Cu/Zn-Containing Superoxide Dismutase in the Heart of Stroke-Prone Spontaneously Hypertensive Rats

Abstract: Although angiotensin II type 1 (AT1) receptor antagonists and angiotensin-converting enzyme (ACE) inhib

Cited by 42 publications

References 32 publications

Is Cardiac Hypertrophy in Spontaneously Hypertensive Rats the Cause or the Consequence of Oxidative Stress?

Is Cardiac Hypertrophy in Spontaneously Hypertensive Rats the Cause or the Consequence of Oxidative Stress?

Inhibition of Rac1-Derived Reactive Oxygen Species in Nucleus Tractus Solitarius Decreases Blood Pressure and Heart Rate in Stroke-Prone Spontaneously Hypertensive Rats

Inhibition of Inward Rectifier K+ Currents by Angiotensin II in Rat Atrial Myocytes: Lack of Effects in Cells from Spontaneously Hypertensive Rats

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