3-nitrotyrosine and Hypertrophy--Left-Ventricular

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases that limits nitric oxide bioavailability. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) exerts a critical role for ADMA degradation and plays an important role in NO signaling. In the heart, DDAH1 is observed in endothelial cells and in the sarcolemma of cardiomyocytes. While NO signaling is important for cardiac adaptation to stress, DDAH1 impact on cardiomyocyte homeostasis is not clear. Here we used the MerCreMer-LoxP model to specifically disrupt cardiomyocyte DDAH1 expression in adult mice to determine the physiological impact of cardiomyocyte DDAH1 under basal conditions and during hypertrophic stress imposed by transverse aortic constriction (TAC). Under control conditions, cardiomyocyte-specific DDAH1 knockout (cDDAH KO) had no detectable effect on plasma ADMA and left ventricular (LV) hypertrophy or function in adult or aging mice. In response to TAC, DDAH1 levels were elevated 2.5-fold in WT mice, which exhibited no change in LV or plasma ADMA content and moderate LV hypertrophy and LV dysfunction. In contrast, cDDAH1 KO mice exposed to TAC showed no increase in LV DDAH1 expression, slightly increased LV tissue ADMA levels, no increase in plasma ADMA, but significantly exacerbated LV hypertrophy, fibrosis, nitrotyrosine production, and LV dysfunction. These findings indicate cardiomyocyte DDAH1 activity is dispensable for cardiac function under basal conditions, but plays an important role in attenuating cardiac hypertrophy and ventricular remodeling under stress conditions, possibly through locally confined regulation of subcellular ADMA and NO signaling.

Topics: Amidohydrolases; Animals; Arginine; Atrial Natriuretic Factor; Disease Models, Animal; Fibrosis; Genetic Predisposition to Disease; Hypertrophy, Left Ventricular; Male; Mice, Knockout; Myocytes, Cardiac; Nitric Oxide; Phenotype; Signal Transduction; Tyrosine; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

The Goto-Kakizaki (GK) rat, a non-obese model of type 2 diabetes mellitus (T2DM), was generated by the selective inbreeding of glucose-intolerant Wistar rats. This is a convenient model for studying diabetes-induced cardiomyopathy independently from the effects of the metabolic syndrome. We investigated the myocardial functional and structural changes and underlying molecular pathomechanisms of short-term and mild T2DM. The presence of DM was confirmed by an impaired oral glucose tolerance in the GK rats compared with the age-matched nondiabetic Wistar rats. Data from cardiac catheterization showed that in GK rats, although the systolic indexes were not altered, the diastolic stiffness was increased compared with nondiabetics (end-diastolic-pressure-volume-relationship: 0.12 ± 0.04 vs. 0.05 ± 0.01 mmHg/μl, P < 0.05). Additionally, DM was associated with left-ventricular hypertrophy and histological evidence of increased myocardial fibrosis. The plasma pro-B-type natriuretic peptide, the cardiac troponin-T, glucose, and the urinary glucose concentrations were significantly higher in GK rats. Among the 125 genes surveyed using PCR arrays, DM significantly altered the expression of five genes [upregulation of natriuretic peptide precursor-A and connective tissue growth factor, downregulation of c-reactive protein, interleukin-1β, and tumor necrosis factor (TNF)-α mRNA-level]. Of the altered genes, which were evaluated by Western blot, only TNF-α protein expression was significantly decreased. The ECG recordings revealed no significant differences. In conclusion, while systolic dysfunction, myocardial inflammation, and abnormal electrical conduction remain absent, short-term and mild T2DM induce the alteration of cardiac TNF-α at both the mRNA and protein levels. Further assessments are required to reveal if TNF-α plays a role in the early stage of diabetic cardiomyopathy development.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Blood Glucose; C-Reactive Protein; Connective Tissue Growth Factor; Diabetes Mellitus, Type 2; Down-Regulation; Echocardiography; Electrocardiography; Fibrosis; Glucose Tolerance Test; Glycosuria; Hypertrophy, Left Ventricular; Immunohistochemistry; In Situ Nick-End Labeling; Inflammation; Interleukin-1beta; Male; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Polymerase Chain Reaction; Rats; Rats, Wistar; RNA, Messenger; Signal Transduction; Troponin T; Tumor Necrosis Factor-alpha; Tyrosine; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Hypertension induces left-ventricular hypertrophy (LVH) by mechanisms involving oxidative stress and unbalanced cardiac matrix metalloproteinase (MMP) activity. We hypothesized that β1-adrenergic receptor blockers with antioxidant properties (nebivolol) could reverse hypertension-induced LVH more effectively than conventional β1-blockers (metoprolol) when used at doses that exert similar antihypertensive effects. Two-kidney one-clip (2K1C) hypertension was induced in male Wistar rats. Six weeks after surgery, hypertensive and sham rats were treated with nebivolol (10 mg kg(-1)day(-1)) or metoprolol (20 mg kg(-1)day(-1)) for 4 weeks. Systolic blood pressure was monitored weekly by tail-cuff plethysmography. LV structural changes and fibrosis were studied in hematoxylin/eosin- and picrosirius-stained sections, respectively. Cardiac MMP levels and activity were determined by in situ zymography, gel zymography, and immunofluorescence. Dihydroethidium and lucigenin-derived chemiluminescence assays were used to assess cardiac reactive oxygen species (ROS) production. Nitrotyrosine levels were determined in LV samples by immunohistochemistry and green fluorescence and were evaluated using the ImageJ software. Cardiac protein kinase B/Akt (AKT) phosphorylation state was assessed by Western blot. Both β-blockers exerted similar antihypertensive effects and attenuated hypertension-induced cardiac remodeling. Both drugs reduced myocyte hypertrophy and collagen deposition in 2K1C rats. These effects were associated with lower cardiac ROS and nitrotyrosine levels and attenuation of hypertension-induced increases in cardiac MMP-2 levels and in situ gelatinolytic activity after treatment with both β-blockers. Whereas hypertension increased AKT phosphorylation, no effects were found with β-blockers. In conclusion, we found evidence that two β1-blockers with different properties attenuate hypertension-induced LV hypertrophy and cardiac collagen deposition in association with significant cardiac antioxidant effects and MMP-2 downregulation, thus suggesting a critical role for β1-adrenergic receptors in mediating those effects. Nebivolol is not superior to metoprolol, at least with respect to their capacity to reverse hypertension-induced LVH.

Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Antihypertensive Agents; Antioxidants; Benzopyrans; Blood Pressure; Down-Regulation; Ethanolamines; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Kidney; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase Inhibitors; Metoprolol; Nebivolol; Oxidative Stress; Phosphorylation; Proto-Oncogene Proteins c-akt; Random Allocation; Rats; Rats, Wistar; Reactive Oxygen Species; Tyrosine; Ventricular Remodeling

Recent data would suggest pre-menopausal insulin resistant women are more prone to diastolic dysfunction than men, yet it is unclear why. We and others have reported that transgenic (mRen2)27 (Ren2) rats overexpressing the murine renin transgene are insulin resistant due to oxidative stress in insulin sensitive tissues. As increased salt intake promotes inflammation and oxidative stress, we hypothesized that excess dietary salt would promote diastolic dysfunction in transgenic females under conditions of excess tissue Ang II and circulating aldosterone levels.. For this purpose we evaluated cardiac function in young female Ren2 rats or age-matched Sprague-Dawley (SD) littermates exposed to a high (4%) salt or normal rat chow intake for three weeks.. Compared to SD littermates, at 10weeks of age, female Ren2 rats fed normal chow showed elevations in left ventricular (LV) systolic pressures, LV and cardiomyocyte hypertrophy, and displayed reductions in LV initial filling rate accompanied by increases in 3-nitrotyrosine content as a marker of oxidant stress. Following 3weeks of a salt diet, female Ren2 rats exhibited no further changes in LV systolic pressure, insulin resistance, or markers of hypertrophy but exaggerated increases in type 1 collagen, 3-nitrotryosine content, and diastolic dysfunction. These findings occurred in parallel with ultrastructural findings of pericapillary fibrosis, increased LV remodeling, and mitochondrial biogenesis.. These data suggest that a diet high in salt in hypertensive female Ren2 rats promotes greater oxidative stress, maladaptive LV remodeling, fibrosis, and associated diastolic dysfunction without further changes in LV systolic pressure or hypertrophy.

Topics: Animals; Collagen; Female; Fibrosis; Fluorescent Antibody Technique; Heart Failure, Diastolic; Hemodynamics; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Microscopy, Electron, Transmission; Mitochondria, Heart; Myocardium; Oxidative Stress; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Sodium, Dietary; Tyrosine; Ventricular Function, Left

This study was designed to evaluate the in vivo cardioprotective effects of food-derived sesamin in spontaneously hypertensive rats (SHR). The study was performed with 17-week-old male normotensive Wistar-Kyoto rats (WKY) and SHR which are untreated or treated with orally administered sesamin for 16 weeks before they were sacrificed. Long-term treatment with sesamin obviously improved left ventricular (LV) hypertrophy and fibrosis in SHR, as indicated by the decrease of LV weight/body weight, myocardial cell size, cardiac fibrosis and collagen type I expression as well as the amelioration of the LV ultrastructure. These effects were associated with reduced systolic blood pressure, enhanced cardiac total antioxidant capability and decreased malondialdehyde content, nitrotyrosine level and transforming growth factor β1 (TGF-β1) expression. All these results suggest that chronic treatment with sesamin improves LV remodeling in SHR through alleviation of oxidative and nitrative stress, reduction of blood pressure and downregulation of TGF-β1 expression.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Collagen Type I; Dioxoles; Disease Models, Animal; Down-Regulation; Fibrosis; Heart; Hypertension; Hypertrophy, Left Ventricular; Lignans; Male; Malondialdehyde; Myocytes, Cardiac; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Transforming Growth Factor beta1; Tyrosine; Ventricular Remodeling

In addition to inotropic effects, cardiac glycosides exert deleterious effects on the heart which limit their use for cardiac therapeutics. In this study, we determined the possible contribution of ouabain-induced iNOS stimulation to the resultant hypertrophic as well as cytotoxic effects of the glycoside on cultured adult rat ventricular myocytes. Myocytes were treated with ouabain (50 μM) for up to 24 h. Ouabain significantly increased gene and protein levels of inducible nitric oxide synthase (iNOS) which was associated with significantly increased release of NO from myocytes as well as increased total release of reactive oxygen species (ROS), superoxide anion (O(2) (-)), and increased peroxynitrite formation as assessed by protein tyrosine nitration. Administration of ouabain was also associated with increased levels of myocyte toxicity as determined by myocyte morphology, trypan blue staining and lactate dehydrogenase (LDH) efflux. The nonspecific NOS inhibitor Nω-nitro-L: -arginine methyl ester and the more selective iNOS inhibitor 1400W both abrogated the increase in LDH release but had no significant effect on either morphology or trypan blue staining. Ouabain also significantly increased both myocyte surface area and expression of atrial natriuretic peptide indicating a hypertrophic response with both parameters being completely prevented by NOS inhibition. The effects of iNOS inhibitors were associated with diminished ouabain tyrosine nitration as well as abrogation of ouabain-induced p38 and ERK phosphorylation. Our study shows that ouabain is a potent inducer of NO formation, iNOS upregulation, and increased production of ROS. Inhibition of ouabain-dependent peroxynitrite formation may contribute to the antihypertrophic effect of iNOS inhibition possibly by preventing downstream MAPK activation.

Topics: Animals; Cardiotonic Agents; Cell Shape; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme Induction; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Hypertrophy, Left Ventricular; L-Lactate Dehydrogenase; Male; Myocytes, Cardiac; Nitric Oxide; Nitric Oxide Synthase Type II; Ouabain; p38 Mitogen-Activated Protein Kinases; Peroxynitrous Acid; Phosphorylation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Superoxides; Time Factors; Tyrosine; Up-Regulation

Ayurveda is an Indian system of medicine. Despite clinical efficacy, lack of scientific validation has limited the effective use of Ayurvedic drugs. Cardoguard is an Ayurvedic antihypertensive drug formulated by Nagarjuna Herbal Concentrates Ltd., Kerala, India. Left ventricular hypertrophy (LVH) is a modifiable risk factor, and regression of LVH reduces the propensity for adverse cardiovascular events. This study was taken up with the objective of evaluating the efficacy of Cardoguard in the prevention of cardiac remodeling. Cardoguard was administered orally to 2-month-old spontaneously hypertensive rats for 4 months at a dose of 5 mg·day(-1). The dose corresponds to the therapeutic dose calculated on the basis of body surface area. Lower hypertrophy index, decrease in cardiomyocyte area, and reduction of interstitial fibrosis in treated spontaneously hypertensive rats indicate amelioration of cardiac hypertrophy by Cardoguard. Cardiac output increased in response to treatment. Immunostaining for the phosphorylated components of major signaling pathways associated with hypertrophy suggests that prevention of LVH by Cardoguard is possibly mediated through inhibition of extracellular signal-regulated kinases and protein kinase C-ε signaling pathways. Reduced expression of 3-nitrotyrosine in response to the treatment suggests that prevention of cardiac remodeling by Cardoguard is mediated by reduction of oxidative stress.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Cardiac Output; Cardiotonic Agents; Endomyocardial Fibrosis; Extracellular Signal-Regulated MAP Kinases; Heart; Hypertrophy, Left Ventricular; Male; MAP Kinase Signaling System; Medicine, Ayurvedic; Myocytes, Cardiac; Oxidative Stress; Protein Kinase C-epsilon; Rats; Rats, Inbred SHR; Rats, Wistar; Signal Transduction; Tyrosine; Ventricular Remodeling

Increased levels of homocysteine (Hcy), recognized as hyperhomocysteinemia (HHcy), were associated with cardiovascular diseases. There was controversy regarding the detrimental versus cardio protective role of inducible nitric oxide synthase (iNOS) in ischemic heart disease. The aim of this study was to test the hypothesis that the Hcy generated nitrotyrosine by inducing the endothelial nitric oxide synthase, causing endothelial-myocyte (E-M) coupling. To differentiate the role of iNOS versus constitutive nitric oxide synthase (eNOS and nNOS) in Hcy-mediated nitrotyrosine generation and matrix remodeling in cardiac dysfunction, left ventricular (LV) tissue was analyzed from cystathionine beta synthase (CBS) heterozygote knockout, iNOS homozygote knockout, CBS-/+/iNOS-/- double knockout, and wild-type (WT) mice. The levels of nitrotyrosine, MMP-2 and -9 (zymographic analysis), and fibrosis (by trichrome stain) were measured. The endothelial-myocyte function was determined in cardiac rings. In CBS-/+ mice, homocysteine was elevated and in iNOS-/- mice, nitric oxide was significantly reduced. The nitrotyrosine and matrix metalloproteinase-9 (MMP-9) levels were elevated in double knockout and CBS-/+ as compared to WT mice. Although MMP-2 levels were similar in CBS-/+, iNOS-/-, and CBS-/+/iNOS-/-, the levels were three- to fourfold higher than WT. The levels of collagen were similar in CBS-/+ and iNOS-/-, but they were threefold higher than WT. Interesting, the levels of collagen increased sixfold in double knockouts, compared to WT, suggesting synergism between high Hcy and lack of iNOS. Left ventricular hypertrophy was exaggerated in the iNOS-/- and double knockout, and mildly increased in the CBS-/+, compared to WT mice. The endothelial-dependent relaxation was attenuated to the same extent in the CBS-/+ and iNOS-/-, compared to WT, but it was robustly blunted in double knockouts. The results concluded that homocysteine generated nitrotyrosine in the vicinity of endothelium, caused MMP activation and endothelium-myocyte uncoupling. The generation of nitrotyrosine was independent of iNOS.

Topics: Animals; Collagen; Cystathionine beta-Synthase; Endothelium, Vascular; Genotype; Homocysteine; Hypertrophy, Left Ventricular; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Knockout; Muscle Cells; Nitric Oxide Synthase Type II; Phenotype; Tyrosine; Ventricular Remodeling

Although aldosterone, acting via mineralocorticoid receptors, causes left ventricular (LV) hypertrophy in experimental models of high-aldosterone hypertension, little is known about the role of aldosterone or mineralocorticoid receptors in mediating adverse remodeling in response to chronic pressure overload.. We used the mineralocorticoid receptor-selective antagonist eplerenone (EPL) to test the role of mineralocorticoid receptors in mediating the transition from hypertrophy to failure in mice with chronic pressure overload caused by ascending aortic constriction (AAC). One week after AAC, mice were randomized to regular chow or chow containing EPL (200 mg/kg per day) for an additional 7 weeks. EPL had no significant effect on systolic blood pressure after AAC. Eight weeks after AAC, EPL treatment improved survival (94% versus 65%), attenuated the increases in LV end-diastolic (3.4+/-0.1 versus 3.7+/-0.1 mm) and end-systolic (2.0+/-0.1 versus 2.5+/-0.2 mm) dimensions, and ameliorated the decrease in fractional shortening (42+/-2% versus 34+/-4%). EPL also decreased myocardial fibrosis, myocyte apoptosis, and the ratio of matrix metalloproteinase-2/tissue inhibitor of matrix metalloproteinase-2. These beneficial effects of EPL were associated with less myocardial oxidative stress, as assessed by 3-nitrotyrosine staining, reduced expression of the adhesion molecule intercellular adhesion molecule-1, and reduced infiltration by macrophages.. Mineralocorticoid receptors play an important role in mediating the transition from LV hypertrophy to failure with chronic pressure overload. The effects of mineralocorticoid receptor stimulation are associated with alterations in the interstitial matrix and myocyte apoptosis and may be mediated, at least in part, by oxidative stress and inflammation.

Topics: Animals; Aorta; Apoptosis; Blood Pressure; Cell Size; Chronic Disease; Constriction, Pathologic; Drug Evaluation, Preclinical; Eplerenone; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Intercellular Adhesion Molecule-1; Ligation; Male; Matrix Metalloproteinases; Mice; Mineralocorticoid Receptor Antagonists; Myocarditis; Myocardium; Myocytes, Cardiac; Oxidative Stress; Pressure; Random Allocation; Receptors, Mineralocorticoid; Spironolactone; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tyrosine

Although NO derived from endothelial NO synthase (eNOS) is thought to be cardioprotective, the role of inducible NO synthase (iNOS) remains controversial. Using mice lacking iNOS (iNOS-/-), we studied (1) whether development of hypertension, cardiac hypertrophy, and dysfunction after deoxycorticosterone acetate (DOCA)-salt would be less severe compared with wild-type controls (WT; C57BL/6J), and (2) whether the cardioprotection attributable to lack of iNOS is mediated by reduced oxidative stress. Mice were uninephrectomized and received either DOCA-salt (30 mg/mouse SC and 1% NaCl+0.2% KCl in drinking water) or vehicle (tap water) for 12 weeks. Systolic blood pressure (SBP) was measured weekly. Left ventricular (LV) ejection fraction (EF) by echocardiography and cardiac response to isoproterenol (50 ng/mouse IV) were studied at the end of the experiment. Expression of eNOS and iNOS as well as the oxidative stress markers 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) were determined by Western blot and immunohistochemical staining, respectively. DOCA-salt increased SBP and LV weight similarly in both strains and decreased EF in WT but not in iNOS-/-. Cardiac contractile and relaxation responses to isoproterenol were greater, 4-HNE and nitrotyrosine levels were lower, and eNOS expression tended to be higher in iNOS-/-. We conclude that lack of iNOS leads to better preservation of cardiac function, which may be mediated by reduced oxidative stress and increased eNOS; however, it does not seem to play a significant role in preventing DOCA-salt-induced hypertension and hypertrophy.

Topics: Aldehydes; Animals; Blood Pressure; Cardiotonic Agents; Desoxycorticosterone; Heart; Hypertension; Hypertrophy, Left Ventricular; Isoproterenol; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Sodium Chloride; Tyrosine

Hydroxymethylglutaryl-coenzyme A reductase inhibitors prevent load-induced left ventricular hypertrophy (LVH). Whether this effect is related to antioxidant properties of this class of drugs is poorly understood. The aim of the present report was to evaluate the regulation of nitrotyrosine production during the development of load-induced LVH and the effect of simvastatin treatment in this process. Rats were subjected to aortic constriction up to 15 days. LVH was evaluated by left/right ventricle mass ratio. Myocardial content of nitrotyrosine, nitric oxide synthase (NOS) isoforms, and phagocyte-type NAD(P)H-oxidase subunits (p67-phox and p22-phox) were analyzed by immunoblotting and immunohistochemistry assays. Another group of rats received treatment with either simvastatin or placebo for 15 days after the onset of pressure overload, and their hearts were also studied. Myocardial nitrotyrosine content was increased from 3 to 15 days of pressure overload in regions of cardiac myocytes in close apposition to myocardial stroma during LVH. Neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS) isoforms had their expression increased in coronary vessels (nNOS and iNOS) and in myocardial stroma (eNOS) from day 3 to day 7 of aortic constriction. However, p67-phox and p22-phox expression was increased in cells of myocardial stroma in parallel to augmented myocardial nitrotyrosine content. Simvastatin treatment inhibited the increases in myocardial nitrotyrosine content and in p67-phox and p22-phox expression, and significantly reduced LVH. In conclusion, antioxidant properties of simvastatin might play a role in myocardial remodeling induced by pressure overload.

Topics: Animals; Antioxidants; Aorta; Constriction; Coronary Vessels; Enzyme Induction; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Isoenzymes; Male; Membrane Transport Proteins; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; NADPH Dehydrogenase; NADPH Oxidases; Nitric Oxide Synthase; Oxidative Stress; Phosphoproteins; Pressure; Proteins; Rats; Rats, Wistar; Simvastatin; Tyrosine; Ventricular Remodeling

Endothelium-dependent G-protein mediated relaxations of epicardial coronary arteries is impaired with left ventricular hypertrophy. The objective of this study was to assess the effect of L-arginine, BH(4) and the combination of two antioxidants, superoxide dismutase and catalase, on endothelium-dependent relaxations in a swine left ventricular hypertrophy model.. Aortic banding was performed 3 cm above the coronary ostia. Vascular reactivity studies were performed in standard organ chamber experiments to assess the NO pathway in the presence of methyltetrahydropterin (a BH(4) analogue), L-arginine, superoxide dismutase and catalase.. There was a statistically significant increase in endothelium-dependent relaxation to serotonin and to bradykinin with methyltetrahydropterin and with superoxide dismutase plus catalase (P<0.05) but not with L-arginine compared to untreated coronary arteries from left ventricular hypertrophy animals. Plasma 3-nitrotyrosine level increased significantly from 918+/-122 to 1844+/-300 microM (P<0.05 vs. control) after 60 days of aortic banding. Endothelial dysfunction was not associated with a reduced expression of endothelial nitric oxide synthase 2 months after pressure overload left ventricular hypertrophy.. Treatment with BH(4) and antioxidants constitutes an interesting approach for the prevention of endothelial dysfunction in epicardial coronary arteries associated with left ventricular hypertrophy.

Topics: Animals; Antioxidants; Arginine; Biomarkers; Bradykinin; Catalase; Coronary Vessels; Dose-Response Relationship, Drug; Echocardiography; Endothelium, Vascular; Female; Hemodynamics; Hypertrophy, Left Ventricular; In Vitro Techniques; Ketanserin; Male; Models, Animal; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Oxidative Stress; Peroxynitrous Acid; Pterins; Serotonin; Serotonin Antagonists; Superoxide Dismutase; Swine; Tyrosine