ascorbic-acid and Hypertrophy--Left-Ventricular

Indirect observations are compatible with cardiac vitamin C deficiency as one contributory factor to oxidative stress in heart failure, but data on ventricular vitamin C content are lacking. Here, we used the well established model of aortic-banded rats at the stage of compensated hypertrophy (6 weeks after banding) and at the transition to cardiac failure (22 weeks after banding) to analyze vitamin C, vitamin E, protein carbonyls and malondialdehyde tissue content together with the respective plasma concentrations. Furthermore, we investigated the expression of the vitamin C transporters SVCT1 and SVCT2 in the left ventricle (LV). Aortic-banded rats, independently from their age, had higher malondialdehyde and protein carbonyl levels in plasma and LV tissue compared to sham-operated animals indicating increased oxidative stress. Plasma vitamin C remained unaffected from cardiac overload, while LV vitamin C was elevated in both stages of hypertrophy together with an increased expression of the vitamin C transporter SVCT2 suggesting increased vitamin C uptake. The levels of antioxidants and lipid peroxides were similar 6 and 22 weeks after aortic banding. Therefore, the accumulation of vitamin C in compensated hypertrophy and in decompensated failure excludes cardiac vitamin C deficiency as a primary factor to oxidative stress in this model.

Topics: Animals; Ascorbic Acid; Blotting, Western; Disease Models, Animal; Heart Failure; Hemodynamics; Hypertrophy, Left Ventricular; Lipid Peroxidation; Male; Malondialdehyde; Matrix Metalloproteinase 2; Myocardium; Organic Anion Transporters, Sodium-Dependent; Oxidative Stress; Protein Carbonylation; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Sodium-Coupled Vitamin C Transporters; Symporters; Tissue Inhibitor of Metalloproteinase-1; Vitamin E

Left ventricular hypertrophy (LVH) is a cardiovascular risk factor. A possible role for endothelial dysfunction in this condition was investigated in a Dunkin-Hartley guinea pig aortic-banded pressure overload-induced model of LVH. Aortic banding produced significant elevation of fore- and hindlimb blood pressure (BP), heart-to-body weight ratios, plasma angiotensin II (ANG II), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-alpha) levels, and coronary microvascular endothelial cell (CMEC) NAD(P)H-dependent superoxide (O) production, and a significant decrease in basal and stimulated CMEC cGMP levels. Treatment of aortic-banded animals with the angiotensin-converting enzyme inhibitor quinapril and the antioxidant vitamin C, either alone or in combination, did not affect BP but caused a significant inhibition of the increases in the heart-to-body weight ratio, ANG II, ET-1, and TNF-alpha levels, and O production and restored cGMP responses to levels comparable with sham-operated animals. These data suggest that quinapril and vitamin C are capable of inhibiting LVH development due to pressure overload via mechanisms that involve the inhibition of oxidative stress, an improvement in coronary endothelial function, and increased nitric oxide bioavailability.

Topics: Animals; Aortic Valve Stenosis; Ascorbic Acid; Blood Pressure; Coronary Vessels; Endothelium, Vascular; Guinea Pigs; Hypertension; Hypertrophy, Left Ventricular; Isoquinolines; Male; NAD; NADP; Quinapril; Superoxides; Tetrahydroisoquinolines

Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation. In experimental left ventricular hypertrophy (LVH), this endothelium-dependent LV relaxant response is impaired despite a preserved response to exogenous NO. We investigated the potential role of reactive oxygen species (ROS) in this defect.. Short-term treatment with the antioxidants vitamin C (10 micromol/L) or deferoxamine (500 micromol/L) restored LV relaxant responses to the NO agonists bradykinin (10 nmol/L) and substance P (100 nmol/L) in isolated ejecting hearts of aortic-banded guinea pigs. Substance P decreased the time to onset of LV relaxation (tdP/dt(min)) by -6.8+/-1.7 ms in the presence of vitamin C and by -8.9+/-2.2 ms in the presence of deferoxamine compared with -0.8+/-2.2 ms in the absence of antioxidants (P<0.05 either antioxidant versus control). A similar restoration of relaxant response to substance P was observed in the presence of the superoxide dismutase mimetic, Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (10 micromol/L), but not with tetrahydrobiopterin or L-arginine. Protein expression of the NADPH oxidase subunits gp91-phox and p67-phox and myocardial NADPH oxidase activity were significantly increased (P<0.05) in the banded group compared with shams.. An increase in ROS, most likely derived at least in part from NADPH oxidase, is responsible for the impaired endothelial regulation of LV relaxation in LVH. These are the first data to potentially link increased NADPH oxidase-derived ROS with a defect in cardiac contractile function in a pathological setting.

Topics: Animals; Antioxidants; Arginine; Ascorbic Acid; Biopterins; Deferoxamine; Drug Synergism; Endothelium, Vascular; Free Radical Scavengers; Glutathione; Guinea Pigs; Heart Ventricles; Hypertrophy, Left Ventricular; In Vitro Techniques; Male; Malondialdehyde; Metalloporphyrins; Myocardial Contraction; NADPH Oxidases; Oxidation-Reduction; Reactive Oxygen Species; Substance P