Plasma Nitric Oxide Research Articles

Thrombosis factors and oxidant/antioxidant markers in obese and hypertensive women during pregnancy

Objective. To investigate the oxidative profile and thrombotic markers in obese and hypertensive mothers. Methods. Thirty obese, 28 hypertensive and 34 healthy control mothers were recruited from Tlemcen Hospital, Algeria. Plasma vitamin C, nitric oxide, superoxide anion, erythrocyte glutathione, malondialdehyde, carbonyl proteins and erythrocyte antioxidant enzyme activities and coagulation markers [protein C, protein S, fibrinogen, prothrombin, antithrombin, activated partial thromboplastin time (APTT), lupus anticoagulants (LACs)] were measured. Changes in plasma urea, creatinine, uric acid, glucose and lipid levels were also determined. Results. Plasma glucose concentrations were high in obese mothers, and plasma urea, uric acid and creatinine levels were increased in hypertensive compared with healthy mothers. Obese and hypertensive mothers had low vitamin C and glutathione values, catalase and superoxide dismutase activities, and high triglyceride, superoxide anion, malondialdehyde and carbonyl protein levels compared with control mothers. Plasma nitric oxide levels were enhanced in obese mothers but reduced in hypertensive mothers. Fibrinogen and prothrombin levels were significantly enhanced in obese and hypertensive mothers. Protein C, protein S, antithrombin and APTT values were significantly higher in hypertensive mothers. Only hypertensive mothers were positive for LACs. Conclusion. Obese and hypertensive mothers presented oxidative stress and a pro-thrombotic state. Their oxidative and hemostasis profile should be carefully considered and appropriate management organized.

Role of Alpha 2‐adrenoceptors in Hemodynamic Instability in Rats Under Cooling Stress

Cooling causes hemodynamic instability as changes in blood pressure variability and heart rate variability (BPV, HRV). We observed that increased sympathomyogenic responses (SMR) as changes in very‐low frequency of BPV (VLFBPV) and low frequency of BPV (LFBPV) which were dependent on the evoked pressor to cooling; the present study was designed to examine whether the α2‐adrenoceptor (AR) is involved in such cooling effects of rats. Hemodynamic changes were telemetry monitored throughout the experiments. Vehicle or yohimbine (YOH, 2.5 or 5.0 mg/kg) was administered with a latency (5 min, 30 min) before a cooling impact (CI, 4±2oC). Plasma nitric oxide (NO) was measured in presence or absence of the added hexamethonium (HEX). Spectral powers of high frequency (HF, 0.6‐3.0 Hz), low frequency (LF, 0.2‐0.6 Hz), and very‐low frequency (VLF, 0.02‐0.2 Hz) in BPV bands were compared with those in HRV bands. Results generally showed 1) cooling‐evoked pressor was significantly attenuated after YOH treatment, 2) Compared with vehicle prior to the CI start, YOH produced tachycardia and increased most frequency powers but reduced the normalized HFHRV (nHFHRV), 3) In contrast, compared with control vehicle throughout the CI trial, YOH produced less pressor, more tachycardia, and increased nHFHRV but reduced most the other frequency powers. Besides, the dicrotic notch was undetectable and NO was increased in CI trial after YOH treatment, in which the increase in NO was diminished after HEX addition. This study confirmed a functional role of α2‐AR which is imperative for the immediate SMR to the cooling‐induced hemodynamic instability.

Effects of LPS Endotoxemia on Cardiovascular Parameters and Plasma Nitric Oxide of Ovariectomized Rats

Females of reproductive age have a more active immune system than males, but influence of sex hormones on cardiovascular system have been controversial. The cardiovascular responses of ovariectomized female rats compared with females in estrus phase after immunological challenge with LPS infusion and nitric oxide production have not yet been elucidated. Wistar rats, eight weeks after being subjected to ovariectomy (OVX) or false-OVX (Sham), had their femoral artery and vein catheterized. Cardiovascular parameters were recorded in conscious rats for 2 hours after LPS injection (5 mg / kg, IV), previously treated with saline or L-NAME (10mg / kg). Plasma samples were collected for measurement of nitrite (NO2) by Griess method. LPS promoted four distinct phases in mean arterial pressure (MAP) of the sham group, with hypotension within 10 minutes (DMAP = -27.5 ± 6 mmHg, n = 8). OVX rats did not show this initial drop (DMAP = -4.4 ± 4 mmHg, n = 7); and pretreatment with L-NAME did not alter the pattern of response to LPS. After 2 hours of LPS injection, NO2 plasma levels were higher in OVX (29±0,9 µM, n = 9 versus 21 ± 2µM, n = 9) and group treated with L-NAME prevented this rise (19 ± 1uM, n = 8 versus 14 ± 2 µM, n = 4). Female rats in estrus decrease more pressure to LPS in the first minutes compared to ovarietomized rats. Blockade of NOS did not alter the decrease in MAP, so it is possible that other mediators participate in the hypotension induced by endotoxemia in female rats.

Effect of Acute Resistance Exercise on Arterial Stiffness Indices in Obese Young Men

This study aimed to investigate the effect of acute resistance exercise on arterial stiffness related indices in obese young males. Twenty young college students were recruited for this study, and divided into obesity (BMI ≥ 27, n = 10) and control (BMI ＜ 24, n = 10) groups. Cardio-ankle vascular index (CAVI), systolic arterial pressure (SBP), ankle-brachial index (ABI), plasma nitric oxide (NO) and one repetition maximal test (1 RM) were measured prior to the experiment. On the day of experiment, all subjects performed an acute bout of moderate resistance exercise (6 sessions, 60% 1 RM, 8 repetitions for 3 sets), and then arterial stiffness variables, including CAVI, SBP, ABI and NO were measured immediately (P0) and 30 minutes after (post, P30) resistance exercise. Results indicated that CAVI of both groups were significantly decreased at P0 compared to pre-exercise, but returned to base level at P30. Plasma NO level in obesity group was significantly higher than that of control group, and significantly increased at P30. In addition, there were no significant differences of ABI between preand post-exercise in both groups. The results suggest that an acute bout of resistance exercise was unable to raise the arterial stiffness levels in obese young males, but increased the NO concentrations to promote the function of vascular endothelial cell.

Ulcer Protective and Ulcer Healing Activities of Aqueous and Methanolic Extracts of Leaves of Rumex Bequaertii De Wild (Polygonaceae) in Rats

The aqueous and methanolic extracts of Rumex bequaertii leaves were investigated for their ability to prevent and treated ulceration of the gastric mucosa in animal models.For this, adult male rats three to four months old and weighing on average 180 g were used for both tests. The extracts were tested orally at doses of 125, 250 and 500 mg/kg, on ulcerations experimentally induced by HCl/ethanol and pylorus ligation (acute ulcer) and acetic acid (chronic ulcer).These extracts showed protective and healing properties on ulcer induced models. A dose of 500 mg/kg of the two extracts inhibited ulceration induced by HCl/ethanol by 98.86 and 91.59 % respectively. With pyloric ligation, no significant variation of the volume of gastric juices, pH and gastric acidity was observed compared to the negative control rats. The aqueous extract alone at different doses presented a significant reduction of the ulceration surface resulting from chronic ulcer induced with acetic acid compared to the negative control group that received distilled water. For all three models of gastric ulcer induction used, the mass of mucus significantly increased in the groups that received the extracts. There was no significant variation in plasmatic nitric oxide (NO) concentrationand gastric supernatant of rats treated with both extracts compared to both control groups. These results reveal that the healing process of the extracts is not achieved through the NO pathway. This process could be due to increase in mucus production and thus supports its traditional use of the plant

Apelin inhibits the activation of the nucleotide-binding domain and the leucine-rich, repeat-containing family, pyrin-containing 3 (NLRP3) inflammasome and ameliorates insulin resistance in severely burned rats

Hyperglycemia with insulin resistance remains a challenging problem in severely burned patients. Recent studies indicated the involvement of the nucleotide-binding domain and the leucine-rich, repeat-containing family, pyrin-containing 3 (NLRP3) inflammasome in insulin resistance and a beneficial role of apelin in insulin resistance. Our aim was to investigate whether apelin inhibits the activation of the NLRP3 inflammasome and ameliorates insulin resistance in severely burned rats. Male Wistar rats were subjected to a full-thickness burn injury comprising 40% of the total body surface area and were randomized to receive apelin, N(G)-methyl-L-arginine acetate salt (L-NMMA), and apelin plus treatments with L-NMMA. The following outcome measurements were assessed: apelin/APJ mRNA expression in white adipose tissue (WAT) and muscles, plasma apelin level, and activation of the NLRP3 inflammasome in WAT, Interleukin-1 β, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 levels in plasma, insulin resistance, survival rates, and endothelial nitric oxide synthase phosphorylation in soleus muscles. Severe burn induced a decreased expression of apelin/APJ mRNA in soleus muscles and a decrease in plasma apelin levels. Burn injury with apelin treatment restored plasma apelin level, inhibited NLRP3 inflammasome activity in WAT, and decreased inflammatory cytokine levels in plasma. Rats treated with apelin also showed improved insulin sensitivity and decreased mortality, accompanied by a remarkable induction of endothelial nitric oxide synthase phosphorylation in soleus muscle. Furthermore, the aforementioned effects of apelin were inhibited in part by treatment with L-NMMA. Apelin inhibits the activation of NLRP3 inflammasome, attenuates systemic inflammatory response, ameliorates insulin resistance, and promotes survival after severe burn, in part through an endothelial nitric oxide synthase-dependent pathway.

Increased α1-adrenoreceptor activity is required to sustain blood pressure in female rats under food restriction.

We evaluated the effect of food restriction (FR) on the various reflexes involved in short term cardiovascular regulation; we also evaluated the contribution of the sympathetic nervous systemand of the plasmatic nitric oxide (NO) in the development of the counterregulatory cardiovascular changes triggered by FR. Female rats were subjected to FR for 14 days, and after this period biochemical measurements of biochemical parameters were performed. For physiological tests, animals were anaesthetised, and a catheter was inserted into the femoral artery and vein for the acquisition of blood pressure and heart hate, and drug infusion, respectively.We then tested the Bezold–Jarisch reflex, the baroreflex and chemoreflex and the effect of the infusion of adrenergic receptor antagonists in control and food restricted animals. The rats subjected to severe FR presented biochemical changes characteristic of malnutrition with a great catabolic state. FR also led to hypotension and bradycardia besides reducing the plasmatic concentration of NO. Moreover, activation of the Bezold–Jarisch reflex induced a more pronounced hypotensive response in animals subjected to FR. Intravenous infusion of a α1-adrenoreceptor antagonist induced a greater hypotensive response and a more pronounced tachycardic response in animals under food restriction,while the infusion of β-adrenoreceptor antagonist induced lower increases in blood pressure in these animals. Our results suggest that an increased α1-adrenoreceptor activity in the resistance arteries coupled with a reduction of plasmatic NO contributes in a complementary manner to maintain the blood pressure levels in animals under FR.

The preventive effect of β3 adrenoceptor stimulation against experimentally induced reflux esophagitis.

A β3 adrenoceptor agonist plays an important regulatory role in stimulation of thermogenesis and lipolysis and it appears to have anti-ulcer and spasmolytic effects. So the present aim was to examine the effect of BRL 37344 (a selective B3 adrenoceptor agonist) on reflux esophagitis. Forty-eight rats were divided into twelve sham-operated with BRL 37344 and/or omeprazole with or without indomethacin. RE was induced in rats, then gastric acid output, pH, plasma nitric oxide (NO), esophageal PGE2, malondialdehyde (MDA) and reduced glutathione (GSH) were measured and the esophageal injury was assessed by macroscopic damage score. Pretreatment with BRL significantly increased plasma NO, GSH, decreased acid output, esophageal MDA and esophageal injury in comparison to pretreatment. In addition, there was a no significant increase in esophageal PGE2. It can be concluded that BRL 37344 has an anti-oxidant protective effect in rats with RE.

PLASMA LEVELS OF NITRIC OXIDE METABOLITES ARE LOWER IN HFPEF SUBJECTS COMPARED TO HFREF AND HYPERTENSIVES

Stable plasma nitric oxide metabolites (NOx), predominantly composed of nitrate, are markers of endogenous nitric oxide (NO) production, NO utilization, and dietary intake and may be indicators of vascular health. We enrolled subjects undergoing a clinically-indicated cardiac MRI. Plasma NOx levels

Nicorandil improves myocardial function by regulating plasma nitric oxide and endothelin-1 in coronary slow flow.

BackgroundCoronary slow flow (CSF) is a special coronary microvascular disorder. The pathogenesis and effective therapeutics of CSF remain unclear. This study aimed to evaluate the global and regional functions of the left ventricle (LV) and investigate the efficacy of nicorandil in patients with CSF.Patients and methodsThirty-six patients with CSF in the left anterior descending (LAD) branch and 20 patients with normal coronary arteries were included. Global and regional functions of the LV supplied by LAD were measured using conventional Doppler echocardiography and two-dimensional speckle tracking echocardiography, respectively, within 24 h after coronary angiography. Concentrations of plasma nitric oxide (NO) and endothelin-1 (ET-1) were detected using colorimetry and radioimmunoassay, respectively. The function of the LV and the levels of NO and ET-1 were also investigated before and 90 days after treatment with 15 mg/day of nicorandil.ResultsCompared with the control group, the early diastolic peak velocity (E), E/A ratio, and plasma NO levels were lower, whereas the late diastolic peak flow velocity (A) and plasma ET-1 levels were significantly higher in the CSF group (P<0.05). The longitudinal strain rate peak of the LV was reduced significantly in CSF patients (P<0.001). After treatment, 75% (27/36) of CSF patients were free of chest pain. The values of E peak, E/A ratio, longitudinal strain rate peak, and plasma NO level were increased (P<0.001), whereas the ET-1 level was decreased in CSF patients (P<0.001).ConclusionNicorandil may improve chest pain symptoms and the impaired function of the LV, possibly by increasing plasma NO and reducing ET-1 in CSF.

Pharmacotherapy and analysis of gaseous mediators in hypertensive patients

To evaluate the effect of using antihypertensive classes of drugs of the calcium channel antagonists and inhibitors of angiotensin-converting enzyme in plasma concentrations of hydrogen sulfide and nitric oxide in patients with hypertension. Cross-sectional study with quantitative approach conducted with hypertensive patients in use of antihypertensive classes of drugs: angiotensin-converting enzyme inhibitors or calcium channel antagonists. It was found that the concentration of plasma nitric oxide was significantly higher in hypertensive patients that were in use of angiotensin-converting enzyme inhibitors (p<0.03) and the hydrogen sulphide concentration was significantly higher in hypertensive plasma in use of calcium channel antagonists (p<0.002). The findings suggest that these medications have as additional action mechanism the improvement of endothelial dysfunction by elevate plasma levels of vasodilatory substances.

Polymorphisms of the NOS3 gene in Tunisian patients with Behçet's disease

Behçet's disease (BD) is a multisystem inflammatory disease characterized by recurrent orogenital ulceration, ocular inflammation and skin lesions. Reduced plasma nitric oxide (NO) levels in patients with BD have been implicated in the development of the endothelial abnormalities and thrombotic complications occurring in these patients. Polymorphisms in the endothelial nitric oxide synthase gene (NOS3) have been inconsistently associated with BD. This inconsistency may derive from population stratification secondary to ethnic diversity, and consideration limited to only one rather than combinations of polymorphisms. We studied three genetic variations in the NOS3 gene: a single nucleotide polymorphism in the promoter region -786T>C, in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (4a4b) of the NOS3 gene in 100 unrelated Tunisian patients with BD and 148 healthy controls. In addition, we also examined the association of NOS3 gene haplotypes with BD. Analyses of the Glu298Asp, -786T>C and 4a4b polymorphisms were made by the polymerase chain reaction (PCR) restriction fragment length polymorphism technique and PCR genotyping, respectively. The distribution of the Glu298Asp genotype differed significantly between patients with BD and controls (P = 0.01). Allele Asp298 was significantly more frequent in patients with BD than in controls (P = 0.005, OR = 1.70, 95% CI 1.14-2.54). In contrast, distribution of alleles and genotypes of -786T>C and 4a4b polymorphisms was not different between the control and BD group. However, the frequency of Asp-T-4b haplotype was significantly higher in patients with BD than in healthy controls. By gender, the signification remained only for heterozygous men (P = 0.03) and homozygous women (P = 0.02). These results suggest that Glu298Asp polymorphism of the NOS3 gene is associated with BD susceptibility in Tunisian patients.

A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2 (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax) using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi), when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFN)γ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi) and the boost (analysis at 180 and 230 dpi). Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO) levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells, preserved the number of IFNγ+ cells, increased the expression of IFNγ mRNA but reduced inducible NO synthase mRNA. Vaccine-based immunostimulation with rAd might offer a rational alternative for re-programming the immune response to preserve and, moreover, recover tissue injury in Chagas’ heart disease.

Nitric oxide and prostaglandin metabolites profiling in buffaloes with impending postpartum reproductive disorders

The study was conducted to correlate the periparturient immune status in terms of plasma nitric oxide (NO) and prostaglandin F2α metabolites (PGFM) profile with impending postpartum reproductive disorders in buffaloes. Pregnant buffaloes (40) were observed for occurrence of postpartum reproductive disorders (PRD), i.e. metritis, endometritis and delayed uterine involution during 1 week prepartum to 4 weeks postpartum period. A representative number (6) of buffaloes that did not develop any PRD were included in Gr. 1 (healthy); and the animals with PRD were assigned into Gr. 2 (8). The blood samples were collected at weekly interval from 1 week prepartum to 4 weeks postpartum period. Plasma NO and PGFM were estimated. A significantly higher NO concentration was found at calving (49.00±7.06 vs. 34.44±3.70 μM) and second week (43.60±5.57 vs 24.25±2.34 μM) postpartum in buffaloes affected with PRD as compared to healthy buffaloes. The PGFM level was also higher in buffaloes that developed PRD throughout the periparturient period. However, the concentration of PGFM was significantly higher, particularly at calving (2.51±0.43 vs 1.267±0.30 ng/ml) and second week (1.058±0.22 vs 0.431±0.08 ng/ml) postpartum. Hence, monitoring of plasma nitric oxide and PGFM level would be effective to predict certain reproductive disorders at calving or immediately after parturition in buffaloes.

D-Carvone, a Monoterpene Reverses Alterations in Heart Rate, Nitric Oxide, Aortic Lipids and Enzymatic Antioxidant Status in Nitric Oxide Deficient Hypertensive Rats

The present study was aimed to assess the antihyperlipidemic, antihypertensive and antioxidant effect of D-carvone, a monoterpene against Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertension. Hypertension was prompted in adult male albino rats of the Wistar strain by oral administration of the L-NAME (40 mg/kg body weight) in drinking water for 4 weeks. Rats were treated with D-carvone (5, 10 and 20 mg/kg body weight) for four weeks. L-NAME treated rats exhibited significant increase in water intake, heart rate, aortic lipids level such as triglycerides (TG), total cholesterol (TC), free fatty acids (FFA) and significant decrease in the level of phospholipids (PL), plasma nitric oxide (NO). The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were decreased in erythrocytes of L-NAME induced hypertensive rats. Treatment with D-carvone restored all the above parameters to near normal level. These results suggest that D-carvone acts as an antihyperlipidemic, antihypertensive and antioxidant agent against L-NAME induced hypertensive rats.

High fat diet exacerbates vascular endothelial dysfunction in rats exposed to continuous hypobaric hypoxia

Independently, a high fat diet and hypoxia are associated with vascular endothelial dysfunction (VED) and often occur concurrently in patients. Nevertheless, the effects of a high fat diet on vascular endothelial function combined with hypoxia, a situation occurring with increasing frequency in many parts of the world, remain largely unknown. We investigated the effects of a high fat diet on vascular endothelial function in rats exposed to continuous hypoxia for 4 weeks. Seventy two male Sprague-Dawley rats were randomly divided into 3 groups: a hypoxia group fed regular chow, a combined hypoxia and high fat diet (HFD) group, and for comparison, rats maintained in normoxia, regular chow conditions were set as baseline (BL) group. The experimental data of BL group were obtained at beginning of hypoxia given in the other groups. Continuous hypoxia was induced in a hypobaric chamber maintained at an altitude of 5000 m. Compared to hypoxic conditions alone, hypoxia plus a HFD prevented adaptive changes in plasma nitric oxide (NOx) levels and caused earlier and more severe changes in aortic endothelial structures. Functionally, hypoxia plus a HFD resulted in impaired endothelium-dependent vasorelaxation responses to acetylcholine and altered the bioavailability of the nitric oxide synthase (NOS) substrate L-Arginine. At the molecular level, hypoxia plus a HFD blunted increases in endothelial NOS (eNOS) mRNA and protein in aortic endothelial tissue. Taken together, our findings demonstrate that in the setting of hypoxia, a high fat diet leads to earlier and more severe VED than hypoxia alone. These data have important implications for populations residing at high-altitude, as dietary patterns shift towards increased fat intake.

Evaluation of oxidative DNA damage and antioxidant defense in patients with nasal polyps

ObjectivesThe presence of inflammatory cells indicates the development of epithelial cell injury in nasal polyposis (NP) and the potential for production of high levels of reactive oxygen and nitrogen species. The aim of our study was to clarify the role of oxidative stress and antioxidant status in the deterioration accompanying NP.MethodsTwenty patients (11 men) aged 47.2 ± 17.0 years with nasal polyps were included in the study. Twenty healthy subjects (7 men) aged 48.2 ± 15.3 years formed the control group. The erythrocyte activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and plasma nitric oxide (NO) concentrations were measured. An alkaline comet assay was used to determine the extent of blood lymphocyte DNA damage of oxidized purines as glicosylo-formamidoglicosylase (Fpg) sites, and oxidized pyrimidines as endonuclease III (Nth) sites.ResultsA significant increase of NO (P < 0.05) and non-significant decreases of SOD (P > 0.05), CAT (P > 0.05), and GPx (P > 0.05) were seen in NP patients compared to healthy controls. The level of blood lymphocyte oxidative DNA damage in NP patients was significantly higher compared to the control group (P = 0.01).DiscussionThe blood lymphocyte DNA damage level increased in patients with NP. Elevated DNA damage may be related to overproduction of reactive oxygen and nitrogen species and/or decreased antioxidant protection.

Effect of Enhanced External Counterpulsation and Cardiac Rehabilitation on Quality of Life, Plasma Nitric Oxide, Endothelin 1 and High Sensitive CRP in Patients With Coronary Artery Disease: A Pilot Study.

ObjectiveTo investigate the effect of enhanced external counterpulsation (EECP) on plasma nitric oxide (NO), Endothelin 1 (ET1), high sensitive C-reactive protein (HSCRP) and quality of life (QoL) in patients with coronary artery disease (CAD).MethodsWe conducted a pilot randomized clinical trial in order to evaluate plasma NO, ET1, HSCRP and QoL before and after twenty sessions of EECP (group A) and cardiac rehabilitation (CR, group B) in 42 patients with CAD (21 in each group).ResultsForty-two patients (33 male and 9 female) were included in the study. The mean age was 58.2±10 years. The mean HSCRP was 1.52±0.7 in the EECP group and it was reduced to 1.27±0.4 after intervention. The reduction in HSCRP was not statistically significant in EECP and CR groups with p=0.33 and p=0.27, respectively. There was not significant improvement of NO, ET1, and QoL in the EECP and CR groups shortly after therapy (p>0.05).ConclusionAlthough the short-term EECP treatment in CAD patients improved HSCRP, NO, ET1, and QoL compared with the baseline those improvements are not statistically significant. Further studies are necessary with large study groups and more sessions.

D-Carvone, a Monoterpene Reverses Alterations in Heart Rate, Nitric Oxide, Aortic Lipids and Enzymatic Antioxidant Status in Nitric Oxide Deficient Hypertensive Rats

The present study was aimed to assess the antihyperlipidemic, antihypertensive and antioxidant effect of D-carvone, a monoterpene against Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertension. Hypertension was prompted in adult male albino rats of the Wistar strain by oral administration of the L-NAME (40 mg/kg body weight) in drinking water for 4 weeks. Rats were treated with D-carvone (5, 10 and 20 mg/kg body weight) for four weeks. L-NAME treated rats exhibited significant increase in water intake, heart rate, aortic lipids level such as triglycerides (TG), total cholesterol (TC), free fatty acids (FFA) and significant decrease in the level of phospholipids (PL), plasma nitric oxide (NO). The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were decreased in erythrocytes of L-NAME induced hypertensive rats. Treatment with D-carvone restored all the above parameters to near normal level. These results suggest that D-carvone acts as an antihyperlipidemic, antihypertensive and antioxidant agent against L-NAME induced hypertensive rats.

Elevated circulating endothelial cell-derived microparticle levels in patients with liver cirrhosis: a preliminary report.

Aim of the studyTo determine plausible associations between liver cirrhosis and circulating endothelial cell-derived microparticles (EMPs), vascular endothelial growth factor (VEGF) levels and plasma nitric oxide (NO) metabolites.Material and methodsSixty patients with cirrhosis and 20 healthy control subjects were enrolled in the study. Circulating EMPs from platelet-poor plasma samples were examined by flow cytometry. These microparticles were categorized into endothelial cell-derived activated MPs (EMP-ac) (CD31+ CD42b– AN-V–) and endothelial cell-derived apoptotic MPs (EMP-ap) (CD31+ CD42b– AN-V+). Plasma VEGF levels were measured by enzyme-linked immunosorbent assay. Plasma NO metabolites (NOx–) levels were determined using a Greiss reaction method.ResultsCompared with the healthy control subjects, the patients with cirrhosis showed a significant increase in plasma levels of both phenotypes of EMPs. When the presence of ascites was considered, the plasma levels of EMP-ap were higher (p < 0.01), as well as NOx– (p < 0.05). EMP-ap positively correlated with VEGF level in all cirrhotic patients and this correlation was stronger in decompensated cirrhotic patients. In multivariate logistic regression analysis, the independent factors associated with the presence of ascites were high EMP-ap levels and elevated VEGF levels.ConclusionsElevated plasma levels of EMP-ap in addition to high levels of VEGF might be considered as valuable parameters for predicting the occurrence of ascites in cirrhotic patients.