Vasodilator Effect Of Nitric Oxide Research Articles

Effectiveness of acute L-arginine supplementation on physical performance in strength training: a systematic review and meta-analysis

Background: The oral administration of L-arginine has been related to improved physical performance due to a likely reduction in muscle fatigue, resulting from the vasodilator effect of nitric oxide on skeletal muscle. However, there is no precise and quantitative analysis of the information in the literature. The main objective of this study was to assess the effectiveness of L-arginine supplementation on physical performance in strength training with a systematic review and meta-analysis. We hypothesized that L-arginine supplementation would improve performance capacity and the effects involved in strength training. Methods: The study period was from 2010 to 2020. The inclusion process established articles with well-designed human experiments that included only L-arginine supplementation (without any additional compounds) testing the effects of L-arginine supplementation on sports performance related to strength training; identical experimental conditions in placebo or control group; and publications in the last ten years (until December 31, 2020). Three studies were included that compared L-arginine supplementation with placebo in anaerobic performance tests. Test analysis supplementation with other supplements was removed and there was no gender, age, and ethnicity level. Results: There was no significant heterogeneity (p>0.05) in the analysis of the three selected articles and the effects of L-arginine supplementation in muscular endurance; performance had a mean of 0.26 (95% CI = -0.129; 0.649; p = 0.190), peak torque with a mean of -0.002 (95% CI = -0.531; 0.527; p = 0. 99) of the third series of exercises and, furthermore, when comparing the integrated effect (resistance rate with the peak torque) there was no difference with a mean of 0.168 (95% CI = -0.145; 0.481; p = 0.292). Conclusions: Acute L-arginine supplementation provides no ergogenic effect on strength training performance.

Effectiveness of acute L-arginine supplementation on physical performance in strength training: a systematic review and meta-analysis

Background: The oral administration of L-arginine has been related to improved physical performance due to a likely reduction in muscle fatigue, resulting from the vasodilator effect of nitric oxide on skeletal muscle. However, there is no precise and quantitative analysis of the information in the literature. The main objective of this study was to assess the effectiveness of L-arginine supplementation on physical performance in strength training with a systematic review and meta-analysis. We hypothesized that L-arginine supplementation would improve performance capacity and the effects involved in strength training. Methods: The study period was from 2010 to 2020. The inclusion process established articles with well-designed human experiments that included only L-arginine supplementation (without any additional compounds) testing the effects of L-arginine supplementation on sports performance related to strength training; identical experimental conditions in placebo or control group; and publications in the last ten years (until December 31, 2020). Three studies were included that compared L-arginine supplementation with placebo in anaerobic performance tests. Test analysis supplementation with other supplements was removed and there was no gender, age, and ethnicity level. Results: There was no significant heterogeneity (p>0.05) in the analysis of the three selected articles and the effects of L-arginine supplementation in muscular endurance; performance had a mean of 0.26 (95% CI = -0.129; 0.649; p = 0.190), peak torque with a mean of -0.002 (95% CI = -0.531; 0.527; p = 0. 99) of the third series of exercises and, furthermore, when comparing the integrated effect (resistance rate with the peak torque) there was no difference with a mean of 0.168 (95% CI = -0.145; 0.481; p = 0.292). Conclusions: Acute L-arginine supplementation provides no ergogenic effect on strength training performance.

Relationship between endothelin and nitric oxide pathways in the onset and maintenance of hypertension in children and adolescents

The mechanisms that regulate blood pressure are numerous and complex; one mechanism that plays an important role in this scenario is represented by the balance between the vasoconstrictor effect of endothelin-1 and the vasodilator effect of nitric oxide. While there is agreement on the fact that increased endothelin-1 activity and decreased nitric oxide bioavailability are present in hypertensive adults, the situation is less clear in children and adolescents. Not all studies agree on the finding of an increase in plasma endothelin-1 levels in hypertensive children and adolescents; in addition, the picture is often confused by the concomitant presence of obesity, a condition that stimulates the production of endothelin-1. Furthermore, there is recent evidence that, in younger obese and hypertensive subjects, there is an overproduction of nitric oxide, rather than a reduction. This condition may change over time, causing endothelial dysfunction due to a reduced availability of nitric oxide in hypertensive adolescents. The purpose of this review is to address the main biochemical and pathophysiological aspects of endothelin and nitric oxide involvement in hypertension and to summarize the available scientific evidence on their role in the onset and maintenance of high blood pressure in children and adolescents.

4-Aminopyridine, a Voltage-Gated K+ Channel Inhibitor, Attenuates Nitric Oxide-Mediated Vasodilation of Retinal Arterioles in Rats.

Nitric oxide (NO) is an important regulator of the retinal blood flow. The present study aimed to determine the role of voltage-gated K+ (KV) channels and ATP-sensitive K+ (KATP) channels in NO-mediated vasodilation of retinal arterioles in rats. In vivo, the retinal vasodilator responses were assessed by measuring changes in the diameter of retinal arterioles from ocular fundus images. Intravitreal injection of 4-aminopyridine (a KV channel inhibitor), but not glibenclamide (a KATP channel blocker), significantly attenuated the retinal vasodilator response to the NO donor (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR3). Intravitreal injection of indomethacin (a non-selective cyclooxygenase inhibitor) also reduced the NOR3-induced retinal vasodilator response. The combination of 4-aminopyridine and indomethacin produced a greater reduction in the NOR3-induced response than either agent alone. 4-Aminopyridine had no significant effect on pinacidil (a KATP channel opener)-induced response. These results suggest that the vasodilatory effects of NO are mediated, at least in part, through the activation of 4-aminopyridine-sensitive KV channels in the retinal arterioles of rats. NO exerts its dilatory effect on the retinal vasculature of rats through at least two mechanisms, activation of the KV channels and enhancement of prostaglandin production.

The inflammatory nitric oxide mechanism and its participation in cardiac tissue injuries

Introduction: Nitric oxide exerts an important effect on the mediation of chemical processes, on the transmitting and signaling action on the inflammatory response in different pathological disorders. It has a vasodilatory effect and modulates inflammatory or anti- inflammatory reactions, depending on the cell type and the stimulus. It has the power to produce hemodilation in the muscles (it dilates the blood vessels increasing the blood flow); by this factor, one can associate the greater blood flow with the muscular recovery, process that ends up becoming faster. Objective: Understand the mechanisms by which nitric oxide acts on cardiac lesions and the inflammatory response. Methodology: The databases of CAPES, PubMed and SciELO were used as sources of search. The articles went through a selection filter so that those of greater scientific relevance were selected, based on the selection of articles published in the last 7 years in impact journals. The keywords used in the search include: "nitric oxide" and "heart" or "heart disease" or "heart failure" and "inflammatory mechanism". Results: Since its discovery, nitric oxide has been intriguing researchers about its multiple actions in the human body, as well as in the pharmaceutical industry for its applicability to active drug components. Nitric oxide has already been associated with several functions, emphasizing its importance in vascular relaxation and signaling in inflammatory processes controlling them, being produced locally in the vessels or when inflammation occurs. In some situations, the vasodilatory effect of nitric oxide can be considered potentially beneficial when analyzed in cardiac lesions, to be included in myocardial ischemia. It is noteworthy that nitric oxide in high concentrations may exert a toxic effect, and it occurs in situations of oxidative stress, generation of oxygen intermediates and deficiency of the antioxidant system. Thus, it is clear the importance of a better understanding of nitric oxide, how it acts beneficially in some lesions, what their molecular roles are, to what extent their production leads to toxicity, as it acts in the inflammatory processes of cardiac lesions. Its role in cardiac lesions varies from protection to aggression depending on the amount present in the medium and degree of injury. The major study lesions that alter the nitric oxide balance in cardiac tissue include myocardial ischemia, acute myocardial infarction, and myocardial hypertrophy. Furthermore, plasma levels of nitric oxide are increased in mice infected with T.cruzi (experimental model of Chagas' disease).Discussion and conclusion of the results: Considering the points discussed, it is concluded that nitric oxide plays a crucial role in cardiac lesions, which has a marked influence on the prognosis and clinical evolution of the cardiac lesion. Still, it can aggravate your picture, worsening general condition, when in inadequate concentrations; or improves it when administered and controlled exogenously, providing better perfusion, and reduction in the formation of atherosclerotic plaques, reduction of ischemia among many other functions.

Simultaneously overcome tumor vascular endothelium and extracellular matrix barriers via a non-destructive size-controlled nanomedicine

Tumor vascular endothelium and extracellular matrix (ECM) as the major barriers of anticancer nanomedicine greatly limited the anticancer efficacy of treatment, but few strategies were available to overcome them simultaneously. Thus, herein a strategy was presented to utilize reversible vasodilatation effect of nitric oxide (NO) and size-controlled characteristic of ultrasound responsive liposome (URL) to construct a non-destructive nanomedicine, which was able to cross both obstacles simultaneously. In this work, URL was built as a carrier via forming a gas layer between lipid bilayer to encapsulate small particles PAMAM@DOX (PD, ~10nm) and NO donation-nitrosoglutathione (GSNO). Under ultrasound (US) stimulation, GSNO fastly generated NO that acting on tumor vascular smooth muscle, resulting in tumor vascular vasodilatation, meanwhile the URL lipid bilayer was destroyed, leading to release sharply of small nanoparticles PD. Combination vasodilatory effect of NO and size-controlled characteristic of URL allowed vast drugs to extravasate through endothelial gap and penetrate into tumor deep. Upon different types of cancers vary greatly in vascular structure, two distinctly different tumor, MCF-7 human breast carcinoma and MiaPaCa-2 human pancreatic carcinoma, were chosen to test the anticancer efficacy of URL. As a result, URL-based nanosystem was significantly more effective than the conventional liposome (CL) in tumor treatment, particularly in much less leaky MiaPaCa-2 tumor treatment (tumor therapeutic efficiency of URL/PD/GSNO+US increased by 32.5% and 56.5% compared to CL/DOX in MCF-7 and MiaPaCa-2 tumor treatment). This study offers a new method to enhance tumor drug accumulation along with minimal toxicity for future clinical cancer treatments.

Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.

Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures.

Dietary Nitrate and the Epidemiology of Cardiovascular Disease: Report From a National Heart, Lung, and Blood Institute Workshop.

In view of continuing unanswered questions regarding the geographical and demographic distribution of cardiovascular disease, and recent discoveries about the effects of dietary nitrate on cardiovascular physiology, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop to

Vasodilatory effects of nitric oxide, hydrogen sulfide and sulfur dioxide in rats: Time-dependent interaction study

The vasodilator response of nitric oxide (NO), hydrogen sulfide (H2S) and sulfur dioxide (SO2) were studied todetermine the significance of the actions and interactions of these gasotransmitters for controlling aortic tone in rats. The isometric tension of five separate sets of experiments was recorded. Sodium nitroprusside (SNP; NO donor), sodium disulphide (Na2S; H2S donor), SO2 derivatives and their paired combinations were added to phenylephrine (PE)-induced contraction during the peak value. Then maximal relaxation rate was calculated four times at 5 min intervals. Tetraethylammonium (TEA) and Glibenclamide (GLIB) were applied for investigating the molecular mechanism of the gasses. While, in a separate set of experiments, we used either L-Arginine (L-Arg), L-Cysteine (L-Cyst) or L-nitroarginine methyl ester (L-NAME) before applying gasotransmitters. Highest and prolonged relaxation rate were recorded when SNP was combined with SO2. The combination of Na2S and SO2-induced vasorelaxation was blocked by TEA and GLIB pretreatments. L-Cyst decreased relaxation compared to SNP and vice versa to SO2 induced vasorelaxation. L-Arg markedly attenuated relaxation responses of Na2S and SO2 derivatives. Also, L-NAME delayed relaxation compared to Na2S and SO2. These results suggest that exogenous paired combinations of H2S, NO and SO2 will enhance and elongate the rate of aortic relaxation. Meanwhile, preincubation of aortic rings with precursors attenuate the dilatory effects of exogenous studied gases.

Involvement of prostaglandin I2 in nitric oxide-induced vasodilation of retinal arterioles in rats

The soluble guanylyl cyclase/cGMP system plays an important role in the vasodilator response to nitric oxide (NO) in various vascular beds. However, in rat retinal arterioles, the cyclooxygenase-1/cAMP-mediated pathway contributes to the vasodilator effects of NO, although the specific prostanoid involved remains to be elucidated. In the present study, we investigated the role of prostaglandin I2 and its receptor (prostanoid IP receptor) system in NO-induced vasodilation of rat retinal arterioles in vivo. Fundus images were captured using a digital camera that was equipped with a special objective lens. Changes in diameter of retinal arterioles were assessed. The NO donor (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR3) increased the diameter of retinal arterioles but decreased systemic blood pressure in a dose-dependent manner. Treatment of rats with indomethacin, a non-selective cyclooxygenase inhibitor, markedly attenuated the retinal vasodilator, but not depressor responses to NOR3. The prostanoid IP receptor antagonist 4,5-dihydro-N-[4-[[4-(1-methylethoxy)phenyl]methyl]phenyl]-1H-imadazol-2-amine (CAY10441), and the prostaglandin I2 synthase inhibitor 9α,11α-azoprosta-5Z,13E-dien-1-oic acid (U-51605), both showed similar preventive effects against the NOR3-induced retinal vasodilator response. Neither CAY10441 nor U-51605 showed any significant effects on the depressor response to NOR3. NOR3 enhanced the release of prostaglandin I2 from cultured human retinal microvascular endothelial cells and the NOR3-induced prostaglandin I2 release was almost completely abolished by the cyclooxygenase-1 inhibitor SC-560, but not by the cyclooxygenase-2 inhibitor NS-398. However, NOR3 did not increase the release of prostaglandin I2 from human intestinal microvascular endothelial cells. These results suggest that NO exerts its dilatory effect via cyclooxygenase-1/prostaglandin I2/prostanoid IP receptor signaling mechanisms in the retinal vasculature.

Effect of Sildenafil on Pre-Eclampsia-Like Mouse Model Induced By L-Name.

N(omega)-nitro-L-arginine methyl ester (L-NAME) decreases the vasodilator effect of nitric oxide (NO) and induces pre-eclampsia in mouse. Sildenafil inhibits the degradation of nitric oxide and increases vasodilation. This study aimed to determine the effects of sildenafil citrate on angiogenesis and oxidative stress at the maternal foetal interface on pre-eclampsia-like mouse model induced by L-NAME. Twenty pregnant mice were divided into four groups: (i) vehicle control; (ii) L-NAME; (iii) sildenafil; (4) L-NAME+sildenafil. L-NAME was administered from day 7 of pregnancy and sildenafil from day 8 until day 16; animals were euthanized on day 17. Placental and foetal sizes and weights were measured; lipid peroxide levels and catalase activity in placental homogenates were determined, and placental vascular endothelia were identified by lectin-histochemistry using BSA-I lectin. Western blot analysis was used to determine VEGF expression in placental homogenates. No changes were seen in placental and foetal development in mice with normal pregnancies treated with sildenafil. Treatments with L-NAME reduced significantly the placental weight and average height and decreased the percentage of the endothelial surface. These alterations may be mediated by the reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L-NAME on nitric oxide synthase (NOS) synthesis. This effect was offset by the treatment with sildenafil, with an increase in the percentage of the endothelial surface. In conclusion, our results indicate that treatment with sildenafil on pre-eclampsia mouse model can be used without adverse effects on the concept and its use in the treatment of pre-eclampsia is promising.

Perioperative management of antiplatelet therapy

Worldwide, cardiovascular events represent the major cause of morbidity and mortality. A key role in the pathogenesis of these events is played by platelets. Interventional procedures, with placement of coronary and vascular stents, often represent the preferred therapeutic strategy. Antiplatelet medications are considered first-line therapy in preventing cardiovascular thrombotic events. A wide array of antiplatelet agents is available, each with different pharmacological properties. When patients on antiplatelet agents present for surgery, the perioperative team must design an optimal strategy to manage antiplatelet medications. Each patient is stratified according to risk of developing a cardiovascular thrombotic event and inherent risk of surgical bleeding. After risk stratification analysis, various therapeutic pathways include continuing or discontinuing all antiplatelet agents or maintaining one antiplatelet agent and discontinuing the other. This review focuses on the pharmacological and pharmacokinetic properties of both older and novel antiplatelet drugs, and reviews current literature and guidelines addressing options for perioperative antiplatelet management.

Sildenafil citrate in the treatment of pain in primary dysmenorrhea: a randomized controlled trial

Is a vaginal preparation of sildenafil citrate capable of alleviating acute menstrual pain in patients with primary dysmenorrhea (PD)? A vaginal preparation of sildenafil citrate is capable of alleviating acute menstrual pain in patients with PD with no observed adverse effects. Oral preparations of nitric oxide (NO) donor drugs augment relaxant effects of NO on myometrial cells, reverse the vasoconstriction caused by prostaglandins and successfully alleviate pain, but the incidence of side effects is too high for routine clinical use. Sildenafil citrate inhibits type 5-specific phosphodiesterase (PDE5), thus preventing the degradation of cyclic guanosine monophosphate (cGMP) in the muscle and augmenting the vasodilatory effects of NO. Therefore, by inhibiting PDE5, the tissue remains relaxed and more blood can circulate through. It has been used previously in a vaginal form with no observed side effects, and it enhances endometrial blood flow. A double-blind, randomized, controlled trial comparing vaginal preparation of sildenafil citrate (100 mg single dose) to a placebo in 62 PD patients at the time of painful menstruation was conducted. The primary outcome was total pain relief over 4 consecutive hours (TOPAR4) comparing sildenafil citrate to placebo, where higher TOPAR4 scores represent better pain relief. Secondary outcomes were pain relief as measured by the visual analog scale (VAS) and uterine artery pulsatility index (PI). Subjects were recruited from December 2007 to January 2011. The trial was stopped due to closeout of the funding for the study. Participants were women in good health, were aged 18-35 years and suffered from moderate to severe PD. They were randomized to either vaginal placebo or 100 mg vaginal sildenafil citrate in a 1:1 ratio using random permuted blocks having a block size of 4. At baseline and 1, 2, 3, and 4 h post-treatment, patients were asked to provide assessment of their degree of pain using two scales: (i) pain on the 5-level ordinal scale used for TOPAR4 calculation and (ii) pain level on the VAS. The study ended 4 h after treatment initiation. Twenty-five subjects completed the study. Using the TOPAR4 score, the sildenafil citrate group had significantly better pain relief compared with the placebo group [mean (SD): 11.9 (3.2) versus 6.4 (2.1), respectively; difference in means = 5.3; 95% CI: (2.9,7.6); P < 0.001)]. On the VAS, sildenafil citrate provided better pain relief than placebo at each time point. At the 2-h time point, the PI was significantly lower in the sildenafil citrate group compared with the placebo group [mean (SD): 1.6 (0.6) versus 2.3 (0.5), respectively; difference in means = -0.7; 95% CI: (-1.2, -0.1); P = 0.01)]. Since we did not meet our sample size due to the loss of funding and could not confirm our primary hypothesis, larger studies of longer duration, likely multi-center, are needed to confirm the findings from this study. A number of medications have been investigated to improve the treatment options for PD, but most have proven unsuccessful or to have an unfavorable risk/benefit ratio. Since PD is a condition that most women suffer from and seek treatment for at some point in their lives, our study offers hope that vaginal sildenafil citrate is a safe and effective option for patients who do not desire or are unresponsive to treatments now available on the market. Funding for this study was provided by National Institutes of Health (NIH) grants RO3 TW007438 and K24 HD01476. The authors report no relevant conflicts of interest. NCT00123162 (Clinical trials.gov).

Vasodilators produced during active hyperaemia interact: potassium attenuates the vasodilatory effect of nitric oxide

We previously demonstrated that multiple vasodilators (i.e. nitric oxide (NO), potassium (K+), adenosine (ADO)) are produced in response to skeletal muscle contraction and their ability to produce significant vasodilation differ depending on skeletal muscle stimulation parameters. Given the production of multiple vasodilators resulting from muscle contraction we sought to determine whether the dilators produced altered one another's vasodilatory ability. We tested whether NO's vasodilatory effect was altered in the presence of K+. Using the hamster cremaster muscle preparation in situ we used intravital microscopy to observe arteriolar vasodilation in response to a range of concentrations of an NO donor, S‐nitroso‐N‐acetyl pennicillamine (SNAP, 10−8M‐10−4M) in the absence and the presence of 10mM K+. The vasodilation with 10−8M‐10−4M SNAP (3.1±1.0μm, 7.6±1.4μm, 10.0±1.7μm, 15.7±2.3μm, 17.8±2.1μm respectively) was significantly attenuated in the presence of 10mM K+ (−1.9±1.1μm, −0.2±1.5μm, 1.3±2.5μm, 6.5±3.1μm, 11.5±2.8μm respectively). Our data show that K+ significantly attenuates the vasodilatory effect of NO. Thus, active hyperaemia may not be the sum effects of multiple individual vasodilators but a product of their interactions. This research was funded by NSERC, Canada.

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Autoregulation and mechanotransduction control the arteriolar response to small changes in hematocrit

Here, we present an analytic model of arteriolar mechanics that accounts for key autoregulation mechanisms, including the myogenic response and the vasodilatory effects of nitric oxide (NO) in the vasculature. It couples the fluid mechanics of blood flow in arterioles with solid mechanics of the vessel wall and includes the effects of wall shear stress- and stretch-induced endothelial NO production. The model can be used to describe the regulation of blood flow and NO transport under small changes in hematocrit and to analyze the regulatory response of arterioles to small changes in hematocrit. Our analysis revealed that the experimentally observed paradoxical increase in cardiac output with small increases in hematocrit results from the combination of increased NO production and the effects of a strong myogenic response modulated by elevated levels of WSS. Our findings support the hypothesis that vascular resistance varies inversely with blood viscosity for small changes in hematocrit in a healthy circulation that responds to shear stress stimuli. They also suggest beneficial effects independent of changes in O(2) carrying capacity associated with the postsurgical transfusion of one or two units of blood.

51 Low-dose sodium nitrite relieves myocardial ischaemia in patients with coronary artery disease: a targeted no-donor effect

Introduction Sodium nitrite (NaNO 2 ) became a popular means of treating angina in the 19th century, as its stable chemical structure allowed for cheap preparation and easy storage. However, the effects were slow and unpredictable and so it fell out of favour as more potent and faster-acting agents became available, (eg, organic nitrates). Recent in vitro evidence shows that nitrite (NO 2 - ) exhibits an enhanced vasodilator effect in hypoxia; an environmental modification which encourages its reduction to nitric oxide (NO). Therefore NaNO 2 could potentially be an anti-ischaemic agent at much lower doses than those used historically, and be without the adverse side effects associated with organic nitrates (eg, systemic hypotension and tachyphylaxis). Method A double-blind, placebo-controlled, cross-over study was performed in 10 subjects with proven myocardial ischaemia documented by exercise tolerance testing and coronary angiography. Two dobutamine stress echocardiography (DSE) studies were performed on each subject: one with 0.9% saline and one with NaNO 2 , 1.5 μmol/min for 20 min. This dose of NaNO 2 has previously been shown to be inert in normoxia but to vasodilate hypoxic tissue. Myocardial ischaemia was identified by the peak systolic velocity (PSV) response during DSE in a six basal-wall segment model of the left ventricle. Using placebo study data-set, walls were classified into tertiles: the lowest tertile of responders of PSV to an increase in heart rate (ΔHR) labelled ischaemia (n=18) and the upper tertile control (n=18). Data was divided into four groups according to the study-infusion received and the myocardial-wall examined: saline/ischaemia , NO 2 - /ischaemia , saline/control and NO 2 - /control . Results Data from each stage of each DSE was plotted on a scatter plot graph with change in (ΔHR) on the x-axis and corresponding change in PSV (ΔPSV) on the y-axis (increase in both values compared to baseline), see Abstract 51 figures 1 and 2. Linear regression analysis of the saline/ischaemia group was lower than the NO 2 - /ischaemia group, with no overlap in their 95% CI, see Abstract 51 figure 1. In addition, the linear regression gradient of the NO 2 - /ischaemia group was similar to the saline/control and the NO 2 - /control gradient, see Abstract 51 figure 2. The peak-dose dobutamine values of ΔPSV/ΔHR were different in the saline/ischaemia group compared to the three other groups (ie, saline/ischaemia =3.7±0.6 cm/s/s, NO 2 - /ischaemia =8.2±1.0 cm/s/s, saline/control =10.5±1.1 cm/s/s, NO 2 - /control =8.4±0.7 cm/s/s; p Conclusions Low-dose NaNO 2 delivers a therapeutic effect to ischaemic myocardial tissue in the absence of a vasodilator effect on normoxic tissue. This is the first study in patients to demonstrate a targeted vasodilator effect of NO 2 - to tissues in need only.

Effect Of L-arginine Supplementation On Nitric Oxide And VO2 Max In Healthy Males

INTRODUCTION: Previous research has focused on the effects of IV or orally administered L-arginine (L-arg) and its subsequent enzymatic reduction by nitric oxide synthase to nitric oxide (NO) in respect to benefits for patients with various forms of heart disease. However, L-arg supplementation has not been widely investigated in terms of its possible cardiovascular effect in healthy populations. The benefits of using this supplement in cardiovascular training are related to the vasodilatory effect of NO, and the possible increase in oxygen delivery to the muscles during exercise. PURPOSE: The purpose of this study was to investigate the effects of varying doses of oral L-arg supplementation on NO concentration and maximal oxygen consumption in normal healthy male subjects. METHODS: Twenty-five healthy males 18-30 yrs of age were recruited. Subjects completed an informed consent and health history questionnaire and were measured for anthropometric measured. Testing trials occurred on three separate occasions seven days apart with dosing (HD - high dose [6 g],LD - low dose [3 g], or PLA- placebo) randomly assigned. Testing trials consisted 3 blood draws: pre-supplementation, 25 min post-supplementation, a VO2 max test, and a post-exercise test. NO concentration was measured via venous blood draw and separated with a centrifuge for plasma. Plasma was then analyzed for NO utilizing a total nitric oxide assay kit. RESULTS: No significant effect was observed following L-arg supplementation at rest; however L-arg concentrations did increase from post-treatment to post-exercise (PLA: 29.69 mol/L vs 39.18 μµmol/L; LD: 27.63 μmol/L vs 32.65 μmol/L; HD: 19.53 μmol/L vs 45.58 μmol/L). L-arg supplementation did demonstrate statistical significance within the treatments (p< 0.05) on VO2 max scores within treatments (PLA= 47.524 ml/kg/min, LD= 48.46 ml/kg/min, HD= 48.54 ml/kg/min). CONCLUSIONS: Since no significance was observed when examining NO measures between treatments, the increase in VO2 max scores might be related to other SNS effects not related to NO concentrations. Further research is needed in this particular subject matter to further explain the physiological rationale for the positive impact that was demonstrated by L-arg on cardiovascular endurance and to provide further information in this area.

L-Arginine as a Potential Ergogenic Aid in Healthy Subjects

Dietary supplements containing L-arginine, a semi-essential amino acid, are one of the latest ergogenic aids intended to enhance strength, power and muscle recovery associated with both aerobic and resistance exercise. L-arginine is claimed to promote vasodilation by increasing nitric oxide (NO) production in the active muscle during exercise, improving strength, power and muscular recovery through increased substrate utilization and metabolite removal, such as lactate and ammonia. Research on L-arginine has recently tested this hypothesis, under the assumption that it may be the active compound associated with the vasodilator effects of NO. There were only five acute studies retrieved from the literature that evaluated exercise performance after L-arginine supplementation, three of which reported significant improvements. Regarding studies on chronic effects, eight studies were encountered: four reported enhancements in exercise performance, whilst four reports showed no changes. Whether these improvements in exercise performance - regardless of the aerobic or anaerobic nature of the exercise - can be associated with increases in NO production, has yet to be demonstrated in future studies. Low oral doses (≤20 g) are well tolerated and clinical side effects are rare in healthy subjects. In summary, it is still premature to recommend dietary supplements containing L-arginine as an ergogenic aid for healthy physically active subjects.

Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2

Diabetes mellitus type-2 (DM-2) contributes to atherogenesis by inducing endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In DM-2, the circulating EPC count is low and their functionality is impaired. The mechanisms that underlie this reduced count and impaired functionality are poorly understood. Nitric oxide (NO) is a short-lived signalling molecule that is produced by vascular endothelial cells and participates in the maintenance of vascular tone. NO is also known to participate in other physiological processes, such as cell survival, proliferation, and migration. The bioavailability of NO is reduced in EPCs from DM-2 patients. Interestingly, an inverse relationship exists between the reduction in NO bioavailability in EPCs and the patient's plasma glucose and glycated haemoglobin levels. In addition, NO bioavailability in EPCs correlates with plasma oxidized low-density lipoprotein levels in DM-2. Although this reduction in NO bioavailability could be attributed to oxidative stress in DM-2 patients, it also may be due to impairment of one or more members of the protein signalling cascades that are responsible for NO production. The stimulation of NO production or its signalling cascades in EPCs may increase their numbers and improve their function, thus attenuating endothelium damage, independent of the vasodilatory effects of NO. This review summarizes the metabolic alterations that underlie the molecular mechanisms that may be responsible for EPC decrease and dysfunction in DM-2 with emphasis on the involvement of the NO system.