ascorbic-acid and Hypertension--Pulmonary

Children conceived by assisted reproductive technology (ART) display vascular dysfunction. Its underlying mechanism, potential reversibility and long-term consequences for cardiovascular risk are unknown. In mice, ART induces arterial hypertension and shortens the life span. These problems are related to decreased vascular endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. The aim of this study was to determine whether ART-induced vascular dysfunction in humans is related to a similar mechanism and potentially reversible. To this end we tested whether antioxidants improve endothelial function by scavenging free radicals and increasing NO bioavailability.. In this prospective double-blind placebo controlled study in 21 ART and 21 control children we assessed the effects of a four-week oral supplementation with antioxidant vitamins C (1 g) and E (400 IU) or placebo (allocation ratio 2:1) on flow-mediated vasodilation (FMD) of the brachial artery and pulmonary artery pressure (echocardiography) during high-altitude exposure (3454 m), a manoeuver known to facilitate the detection of pulmonary vascular dysfunction and to decrease NO bioavailability by stimulating oxidative stress. Antioxidant supplementation significantly increased plasma NO measured by ozone-based chemiluminescence (from 21.7 ± 7.9 to 26.9 ± 7.6 µM, p = 0.04) and FMD (from 7.0 ± 2.1 to 8.7 ± 2.0%, p = 0.004) and attenuated altitude-induced pulmonary hypertension (from 33 ± 8 to 28 ± 6 mm Hg, p = 0.028) in ART children, whereas it had no detectable effect in control children.. Antioxidant administration to ART children improved NO bioavailability and vascular responsiveness in the systemic and pulmonary circulation. Collectively, these findings indicate that in young individuals ART-induced vascular dysfunction is subject to redox regulation and reversible.

Topics: Adolescent; Age Factors; Altitude; Antioxidants; Arterial Pressure; Ascorbic Acid; Brachial Artery; Child; Double-Blind Method; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Nitric Oxide; Oxidative Stress; Prospective Studies; Pulmonary Artery; Recovery of Function; Reproductive Techniques, Assisted; Switzerland; Time Factors; Treatment Outcome; Vasodilation; Vitamin E

Pulmonary hypertension in children is commonly caused by underlying cardiac and pulmonary disease. Within the past 10 years, scurvy has been identified as a cause for pulmonary hypertension. We describe the case of a 3-year-old autistic boy with undiagnosed scurvy who was scheduled for cardiac catheterization. Immediately after induction, the patient became hemodynamically unstable, which worsened with administration of nitrous oxide. Cardiac catheterization revealed pulmonary hypertension, which dramatically improved with administration of vitamin C. Anesthesiologists should be aware that scurvy is more common than previously thought, even in developed countries and can cause unexpected circulatory collapse from pulmonary hypertensive crisis.

Topics: Anesthesia, General; Ascorbic Acid; Autistic Disorder; Cardiac Catheterization; Child, Preschool; Humans; Hypertension, Pulmonary; Male; Nitrous Oxide; Scurvy; Treatment Outcome

Topics: Adolescent; Ascorbic Acid; Chest Pain; Cholecalciferol; Dietary Supplements; Echocardiography; Gingiva; Hemorrhage; Humans; Hypertension, Pulmonary; Iron; Leg; Male; Pain; Scurvy; Wounds and Injuries

Ascorbic acid bound to KMUP-1 and sildenafil were examined for their antioxidant effects on vascular endothelium growth factor (VEGF) and endothelium nitric oxide synthase (eNOS) in hypoxic pulmonary artery (PA). Inhaled KMUP-1 and oral sildenafil released NO from eNOS. The effect of buffered l-ascorbic acid, alone and bound to KMUP-1 or sildenafil, for treating pulmonary arterial hypertension (PAH) is unclear. In this study, the antioxidant capacity of ascorbic acid increased the beneficial effects of KMUP-1 on PAH. KMUP-1A and sildenafil-A (5 mg/kg/d) were administered to hypoxic PAH rats. Pulmonary artery blood pressure, and VEGF, Rho kinase II (ROCK II), eNOS, soluble guanylate cyclase (sGC-α), and protein kinase G expression in lung tissues were measured to link PAH and right ventricular hypertrophy. Hypoxic rats had higher pulmonary artery blood pressure, greater PA medial wall thickness and cardiac weight, and a higher right ventricle/left ventricle + septum [RV/(LV+S)] ratio than normoxic rats. Oral KMUP-1A or sildenafil-A for 21 days in hypoxia prevented the rarefaction of eNOS in immunohistochemistry (IHC), reduced the IHC of VEGF in PAs, restored eNOS/protein kinase G/phosphodiesterase 5A; unaffected sGC-α and inactivated ROCK II expression were also found in lung tissues. In normoxic PA, KMUP-1A/Y27632 (10μM) increased eNOS and reduced ROCK II. ROCK II/reactive oxidative species was increased and eNOS was reduced after long-term hypoxia for 21 days. KMUP-1A or Y27632 blunted ROCK II in short-term hypoxic PA at 24 hours. l-Ascorbic acid + l-sodium ascorbate (40, 80μM) buffer alone directly inhibited the IHC of VEGF in hypoxic PA. Finally, KMUP-1A or sildenafil-A reduced PAH and associated right ventricular hypertrophy.

Topics: Amides; Animals; Ascorbic Acid; Endothelium, Vascular; Hypertension, Pulmonary; Hypoxia; Male; Nitric Oxide Synthase Type III; Piperidines; Pulmonary Artery; Pyridines; Rats; Sildenafil Citrate; Vascular Endothelial Growth Factors; Xanthines

We describe the case of a 40-year-old female patient who developed severe pulmonary hypertension and life-threatening right-sided heart failure in association with dietary scurvy and iron deficiency. Supplementation with oral vitamin C and iron very likely contributed to her complete cure. Scurvy-associated pulmonary arterial hypertension could result from impaired availability of endothelial nitric oxide, but inappropriate activation of the hypoxia-inducible family (HIF) of transcription factors could play an even more important role. HIF coordinates the body's responses to hypoxia, and its activity is regulated by oxygen-dependent prolyl hydroxylases, which need vitamin C and iron as cofactors. Deficiency of these cofactors could lead to uncontrolled HIF activity and pulmonary vasoconstriction responsive to vitamin C and iron administration.

Topics: Adult; Anemia, Iron-Deficiency; Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Echocardiography; Female; Heart Failure; Humans; Hypertension, Pulmonary; Iron; Scurvy; Treatment Outcome; Vasoconstriction

Inhaled nitric oxide (NO) has the capacity to selectively dilate pulmonary blood vessels, and thus enhance the matching of ventilation and perfusion, improve oxygenation and decrease pulmonary hypertension. However, existing approaches for the administration of inhaled NO are associated with the co-delivery of potentially toxic concentrations of nitrogen dioxide (NO2) due to the oxidation of NO in oxygen rich environments. We tested the ability of a novel methodology for generating highly purified NO through the reduction of NO2 by ascorbic acid to reverse pulmonary hypertension. In vitro testing demonstrated that the NO output of the novel device is ultrapure and free of NO2. An in vivo hypoxemic swine model of pulmonary hypertension was used to examine the dose response to NO in terms of pulmonary pressures and pulmonary vascular resistance. Pulmonary hypertension was induced by lowering inspired oxygen to 15% prior to treatment with inhaled ultra purified NO (1, 5, 20, and 80PPM). Hypoxemia increased mean pulmonary artery pressures and pulmonary vascular resistance. Inhaled ultra purified NO doses (down to 1PPM) show a marked reduction of hypoxemia-induced pulmonary vascular resistance. These experiments demonstrate a simple and robust method to generate purified inhaled NO that is devoid of NO2 and capable of reversing hypoxemia induced pulmonary hypertension.

Topics: Administration, Inhalation; Animals; Ascorbic Acid; Disease Models, Animal; Hypertension, Pulmonary; Hypoxia; Nitric Oxide; Nitrogen; Nitrogen Dioxide; Oxygen; Pulmonary Artery; Swine; Vascular Resistance

1. This study investigates the time course of pulmonary arterial hypertension (PAH) due to monocrotaline (MCT) and its association with cardiac function and oxidative stress markers in the left ventricle (LV). 2. Male Wistar rats were divided into six groups: 7 days, 21 days, and 31 days for both control and MCT groups. Following echocardiographic analysis, the heart was removed. The LV was separated and homogenized to analyze oxidized-to-total glutathione ratio and thioredoxin reductase (TrxR) activity as well as hydrogen peroxide (H(2) O(2) ) and ascorbic acid levels. 3. There was significant (P < 0.01) cardiac and right ventricle (RV) hypertrophy and pulmonary congestion in the MCT 21 day and 31 day groups. Echocardiography showed a change in the flow wave of the pulmonary artery at 21 days after MCT treatment. There was an increase in the LV ejection time (P < 0.05) at 31 days after MCT. The LV H(2)O(2) concentration was increased (P < 0.05) in the MCT 21 day and MCT 31 day groups compared with controls. There was a reduction (P < 0.05) in the LV ascorbic acid concentration and an increase (P < 0.05) in TrxR activity in the MCT 31 day rats. 4. Our findings showed RV changes due to pulmonary hypertension at 21 days after MCT injection. There was a correlation between the degree of dysfunction and the morphometry of the heart chambers, along with impairment of the antioxidant/pro-oxidant balance in the LV 31 days after the beginning of the protocol. This study suggests that LV changes follow RV dysfunction subsequent to pulmonary hypertension.

Topics: Animals; Ascorbic Acid; Cardiomegaly; Familial Primary Pulmonary Hypertension; Glutathione; Heart Ventricles; Hydrogen Peroxide; Hypertension, Pulmonary; Male; Monocrotaline; Oxidative Stress; Rats; Rats, Wistar; Thioredoxin-Disulfide Reductase; Ultrasonography

Topics: Altitude Sickness; Ascorbic Acid; Endothelin-1; Humans; Hypertension, Pulmonary; Nitric Oxide; Oxidative Stress; Vitamin E

1. The aim of this study was to determine the effects of added dietary vitamin C on the intestinal mucosa morphology in pulmonary hypertensive broiler chickens. 2. One-day-old chickens were reared at high altitude and treated with 400, 800 or 1200 mg vitamin C/l of drinking water for 48 d. Segments from the duodenum, jejunum and ileum were collected for morphometric analysis. 3. The duodenum and jejunum villus height, width, surface area and lamina propria thickness were greater in the highest vitamin C-treated groups compared to controls. 4. There were significant variations only in villus types of the jejunum and ileum: increased proportions of leaf + tongue-like villi and decreased proportions of convoluted + ridge-like villi at day 36 at the groups with 400 and 800 mg vitamin C/l. 5. It was concluded that vitamin C improves the gut morphology of the pulmonary hypertensive broiler chickens.

Topics: Altitude; Animals; Antioxidants; Ascorbic Acid; Chickens; Drinking; Duodenum; Hypertension, Pulmonary; Ileum; Intestinal Mucosa; Jejunum; Poultry Diseases

1. Three hundred and eighty 1-day-old Arbor Acres broilers were divided into control (A) and experimental (B, C, D, and E) groups. 2. After 14 d of age the experimental groups were subjected to a cool temperature challenge by lowering the temperature 1 to 2 degrees C per day down to 12 degrees C, and maintaining this temperature until 7 weeks of age. 3. At the same time, 1.5 mg/kg 3,3,5-triiodothyronine (T3) was added to the diet of groups D and E, and 500 mg/kg ascorbic acid (vitamin C) to the diet of groups C and E. 4. The incidence of pulmonary hypertension syndrome (PHS), body weight gain and feed intake were measured weekly. Lung and blood samples were collected weekly from 10 birds per group beginning on d 14, and the percentage of thick-walled peripheral lung vessels (% TWPV) and packed cell volume (PCV) were determined. 5. The lower ambient temperature and diets supplemented with T3 increased PHS incidence and % TWPV and decreased body weight gain. 6. There was an increase in PCV after 5 weeks of age under lower ambient temperature 3 and the PCV values 14 were also significantly increased by T3. 7. Vitamin C supplementation reduced PHS incidence and % TWPV but did not change packed cell volume, body, weight gain, feed intake, or feed conversion. 8. It is concluded that vitamin C reduced PHS and the associated muscularisation of pulmonary arterioles induced by exposing broilers to cool environmental temperatures and feeding them with T3.

Topics: Animals; Arterioles; Ascorbic Acid; Chickens; Cold Temperature; Dietary Supplements; Hematocrit; Histocytochemistry; Hypertension, Pulmonary; Lung; Poultry Diseases; Random Allocation; Triiodothyronine

1. Three experiments were conducted using a low temperature model to induce pulmonary hypertension (PH) and ascites in broiler chickens. Diets containing 25 g or 50 g flax oil/kg food and control diets with an equivalent amount of animal/vegetable (A/V) blend oil, with and without supplemental antioxidants (vitamin C and vitamin E) were used. The amount of PH was assessed by the ratio of right ventricle weight to total ventricle weight (RV/TV ratio). Birds were considered to suffer from pulmonary hypertension syndrome (PHS) if the RV/TV ratio was greater than 0.299. 2. In experiment 1, the test diets contained 50 g oil/kg food and were given during the grower period only. Birds fed on the flax oil diet tended to have a lower incidence of PHS, ascites and lower RV/TV ratios than birds fed on the control diet. However, when the flax oil diet was supplemented with antioxidants, the incidence of ascites, PHS, haematocrit and whole blood and plasma viscosity increased compared with birds fed on the flax oil diet without antioxidants. These effects were not seen in experiment 2, when the test diets containing 30 g oil/kg food (25 g flax oil plus 5 g A/V blend oil/kg food compared to 30 g A/V blend oil/kg food) were given during the grower period. However, in experiment 3, when the test diets containing 30 g oil/kg food were given from day 1 to week 8, birds fed on the control diet supplemented with antioxidants had a higher incidence of PHS than those fed on the control diet alone. 3. In all 3 experiments, there was no significant effect of dietary fat source or supplemental antioxidants on total food intake or food conversion. 4. We conclude that diets containing 50 g flax oil/kg food tend to reduce the incidence of PHS and ascites in broilers using a low temperature model but the results were not statistically significant. In some cases, supplementing diets with a combination of vitamin E and vitamin C increased the incidence of ascites and PHS.

Topics: Animal Nutritional Physiological Phenomena; Animals; Antioxidants; Ascites; Ascorbic Acid; Chickens; Hypertension, Pulmonary; Incidence; Linseed Oil; Male; Poultry Diseases; Temperature; Vitamin E