Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice

2008 ◽  
Vol 294 (2) ◽  
pp. H1058-H1066 ◽  
Author(s):  
Johannes Jacobi ◽  
Renke Maas ◽  
Nada Cordasic ◽  
Kilian Koch ◽  
Roland E. Schmieder ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Asymmetric Dimethylarginine ◽  
Interstitial Fibrosis ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ ◽  
Ang Ii ◽  
Renal Interstitial Fibrosis

The aim of the present study was to investigate the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and its degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) in angiotensin II (ANG II)-induced hypertension and target organ damage in mice. Mice transgenic for the human DDAH1 gene (TG) and wild-type (WT) mice (each, n = 28) were treated with 1.0 μg·kg−1·min−1 ANG II, 3.0 μg·kg−1·min−1 ANG II, or phosphate-buffered saline over 4 wk via osmotic minipumps. Blood pressure, as measured by tail cuff, was elevated to the same degree in TG and WT mice. Plasma levels of ADMA were lower in TG than WT mice and were not affected after 4 wk by either dose of ANG II in both TG and WT animals. Oxidative stress within the wall of the aorta, measured by fluorescence microscopy using the dye dihydroethidium, was significantly reduced in TG mice. ANG II-induced glomerulosclerosis was similar between WT and TG mice, whereas renal interstitial fibrosis was significantly reduced in TG compared with WT animals. Renal mRNA expression of protein arginine methyltransferase (PRMT)1 and DDAH2 increased during the infusion of ANG II, whereas PRMT3 and endogenous mouse DDAH1 expression remained unaltered. Chronic infusion of ANG II in mice has no effect on the plasma levels of ADMA after 4 wk. However, an overexpression of DDAH1 alleviates ANG II-induced renal interstitial fibrosis and vascular oxidative stress, suggesting a blood pressure-independent effect of ADMA on ANG II-induced target organ damage.

scholarly journals Sodium Intake and Target Organ Damage in Hypertension—An Update about the Role of a Real Villain

2020 ◽  
Vol 17 (8) ◽  
pp. 2811 ◽  
Author(s):  
Federica Nista ◽  
Federico Gatto ◽  
Manuela Albertelli ◽  
Natale Musso
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Sodium Intake ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Main Role ◽  
Sodium Consumption

Salt intake is too high for safety nowadays. The main active ion in salt is sodium. The vast majority of scientific evidence points out the importance of sodium restriction for decreasing cardiovascular risk. International Guidelines recommend a large reduction in sodium consumption to help reduce blood pressure, organ damage, and cardiovascular risk. Regulatory authorities across the globe suggest a general restriction of sodium intake to prevent cardiovascular diseases. In spite of this seemingly unanimous consensus, some researchers claim to have evidence of the unhealthy effects of a reduction of sodium intake, and have data to support their claims. Evidence is against dissenting scientists, because prospective, observational, and basic research studies indicate that sodium is the real villain: actual sodium consumption around the globe is far higher than the safe range. Sodium intake is directly related to increased blood pressure, and independently to the enlargement of cardiac mass, with a possible independent role in inducing left ventricular hypertrophy. This may represent the basis of myocardial ischemia, congestive heart failure, and cardiac mortality. Although debated, a high sodium intake may induce initial renal damage and progression in both hypertensive and normotensive subjects. Conversely, there is general agreement about the adverse role of sodium in cerebrovascular disease. These factors point to the possible main role of sodium intake in target organ damage and cardiovascular events including mortality. This review will endeavor to outline the existing evidence.

Associations between cardiac target organ damage and microvascular dysfunction: the role of blood pressure

2010 ◽  
Vol 28 (5) ◽  
pp. 952-958 ◽  
Author(s):  
William D Strain ◽  
Nish Chaturvedi ◽  
Alun Hughes ◽  
Petros Nihoyannopoulos ◽  
Christopher J Bulpitt ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Target Organ Damage ◽  
Microvascular Dysfunction ◽  
Organ Damage ◽  
Target Organ

Cardiac hypertrophy is associated with altered thioredoxin and ASK-1 signaling in a mouse model of menopause

2008 ◽  
Vol 295 (4) ◽  
pp. H1481-H1488 ◽  
Author(s):  
Talin Ebrahimian ◽  
M. Ram Sairam ◽  
Ernesto L. Schiffrin ◽  
Rhian M. Touyz
Keyword(s):  
Oxidative Stress ◽  
Cardiac Hypertrophy ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Receptor Expression ◽  
Ang Ii ◽  
Antioxidant Function ◽  
Endogenous Antioxidant

Oxidative stress is implicated in menopause-associated hypertension and cardiovascular disease. The role of antioxidants in this process is unclear. We questioned whether the downregulation of thioredoxin (TRX) is associated with oxidative stress and the development of hypertension and target-organ damage (cardiac hypertrophy) in a menopause model. TRX is an endogenous antioxidant that also interacts with signaling molecules, such as apoptosis signal-regulated kinase 1 (ASK-1), independently of its antioxidant function. Aged female wild-type (WT) and follitropin receptor knockout (FORKO) mice (20–24 wk), with hormonal imbalances, were studied. Mice were infused with ANG II (400 ng·kg−1·min−1; 14 days). Systolic blood pressure was increased by ANG II in WT (166 ± 8 vs. 121 ± 5 mmHg) and FORKO (176 ± 7 vs. 115 ± 5 mmHg; P < 0.0001; n = 9/group) mice. In ANG II-infused FORKO mice, cardiac mass was increased by 42% ( P < 0.001). This was associated with increased collagen content and augmented ERK1/2 phosphorylation (2-fold). Cardiac TRX expression and activity were decreased by ANG II in FORKO but not in WT ( P < 0.01) mice. ASK-1 expression, cleaved caspase III content, and Bax/Bcl-2 content were increased in ANG II-infused FORKO ( P < 0.05). ANG II had no effect on cardiac NAD(P)H oxidase activity or on O2•− levels in WT or FORKO. Cardiac ANG II type 1 receptor expression was similar in FORKO and WT. These findings indicate that in female FORKO, ANG II-induced cardiac hypertrophy and fibrosis are associated with the TRX downregulation and upregulation of ASK-1/caspase signaling. Our data suggest that in a model of menopause, protective actions of TRX may be blunted, which could contribute to cardiac remodeling independently of oxidative stress and hypertension.

Metabolic syndrome and target organ damage: role of blood pressure

2008 ◽  
Vol 6 (5) ◽  
pp. 731-743 ◽  
Author(s):  
Cesare Cuspidi ◽  
Carla Sala ◽  
Alberto Zanchetti
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ

Target organ damage in patients with rheumatoid arthritis: The role of blood pressure and heart rate

2010 ◽  
Vol 209 (1) ◽  
pp. 255-260 ◽  
Author(s):  
Vasileios F. Panoulas ◽  
Tracey E. Toms ◽  
Giorgos S. Metsios ◽  
Antonios Stavropoulos-Kalinoglou ◽  
Athanasios Kosovitsas ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Pressure ◽  
Heart Rate ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ

scholarly journals Mitochondrial Dysfunction Contributes to Hypertensive Target Organ Damage: Lessons from an Animal Model of Human Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Speranza Rubattu ◽  
Rosita Stanzione ◽  
Massimo Volpe
Keyword(s):  
Blood Pressure ◽  
Mitochondrial Dysfunction ◽  
Human Disease ◽  
Spontaneously Hypertensive Rat ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ ◽  
Suitable Model ◽  
Human Hypertension

Mechanisms underlying hypertensive target organ damage (TOD) are not completely understood. The pathophysiological role of mitochondrial oxidative stress, resulting from mitochondrial dysfunction, in development of TOD is unclear. The stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable model of human hypertension and of its vascular consequences. Pathogenesis of TOD in SHRSP is multifactorial, being determined by high blood pressure levels, high salt/low potassium diet, and genetic factors. Accumulating evidence points to a key role of mitochondrial dysfunction in increased susceptibility to TOD development of SHRSP. Mitochondrial abnormalities were described in both heart and brain of SHRSP. Pharmacological compounds able to protect mitochondrial function exerted a significant protective effect on TOD development, independently of blood pressure levels. Through our research efforts, we discovered that two genes encoding mitochondrial proteins, one (Ndufc2) involved in OXPHOS complex I assembly and activity and the second one (UCP2) involved in clearance of mitochondrial ROS, are responsible, when dysregulated, for vascular damage in SHRSP. The suitability of SHRSP as a model of human disease represents a promising background for future translation of the experimental findings to human hypertension. Novel therapeutic strategies toward mitochondrial molecular targets may become a valuable tool for prevention and treatment of TOD in human hypertension.

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