UMLS:C0007222 - FACTA Search

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Query: UMLS:C0007222 (cardiovascular disease)
65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric (correction of nitrous) oxide (NO) plays a fundamental part in the haemostatic equilibrium between the endothelium and platelets, an equilibrium of established clinical importance in cardiovascular disease. NO stimulates the enzyme guanylate cyclase which is responsible for synthesis of GMPc, the increase of which results in platelet inhibition. Synthesis of NO may have endogenous auto or paracrine origine from platelets or endothelial cells and participates in the local regulation of platelet function in association with other products of endothelial or platelet synthesis. Exogenous administration is common in therapeutics either in molecules which release NO (nitrate derivatives, sodium nitropruside, molsidomine, etc) or by NO gas administered by inhalation. The antiplatelet effect of NO has been clearly demonstrated in vitro, in vivo or ex vivo, in animals and humans, and probably explains, at least partially, the efficacy of nitrate derivatives in ischaemic coronary artery disease. Nevertheless, the platelet inhibition observed with intravenous NO releasing drugs is associated with potentially harmful systemic hypotension. Platelet inhibition by inhalation of NO could be an alternative means of avoiding this unwanted effect.
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PMID:[Antiplatelet properties of nitrogen monoxide]. 909 14

Nicotine is recognized to be the major inducer of tobacco dependence. The smoking of cigarettes as an advantageous delivery system for nicotine, accelerates and aggravates cardiovascular disease, and is causally associated with increased risks for chronic obstructive lung disease, cancer of the lung and of the upper aerodigestive system, and cancer of the pancreas, renal pelvis, and urinary bladder. It is also associated with cancer of the liver, cancer of the uterine cervix, cancer of the nasal cavity, and myeloid leukemia. In 1950, the first large-scale epidemiological studies documented that cigarette smoking induces lung cancer and described a dose-response relationship between number of cigarettes smoked and the risk for developing lung cancer. In the following decades these observations were not only confirmed by several hundreds of prospective and case-control studies but the plausibility of this causal association was also supported by bioassays and by the identification of carcinogens in cigarette smoke. Whole smoke induces lung tumors in mice and tumors in the upper respiratory tract of hamsters. The particulate matter of the smoke elicits benign and malignant tumors on the skin of mice and rabbits, sarcoma in the connective tissue of rats, and carcinoma in the lungs of rats upon intratracheal instillation. More than 50 carcinogens have been identified, including the following classes of compounds: polynuclear aromatic hydrocarbons (PAH), aromatic amines, and N-nitrosamines. Among the latter, the tobacco-specific N-nitrosamines (TSNA) have been shown to be of special significance. Since 1950, the makeup of cigarettes and the composition of cigarette smoke have gradually changed. In the United States, the sales-weighted average "tar" and nicotine yields have declined from a high of 38 mg "tar" and 2.7 mg nicotine in 1954 to 12 mg and 0.95 mg in 1992, respectively. In the United Kingdom, the decline was from about 32 mg "tar" and 2.2 mg nicotine to less than 12 mg "tar" and 1.0 mg nicotine per cigarette. During the same time, other smoke constituents changed correspondingly. These reductions of smoke yields were primarily achieved by the introduction of filter tips, with and without perforation, selection of tobacco types and varieties, utilization of highly porous cigarette paper, and incorporation into the tobacco blend of reconstituted tobacco, opened and cut ribs, and "expanded tobacco." In most countries where tobacco blends with air-cured (burley) tobacco are used, the nitrate content of the cigarette tobacco increased. In the United States nitrate levels in cigarette tobacco rose from 0.3-0.5% to 0.6-1.35%, thereby enhancing the combustion of the tobacco. More complete combustion decreases the carcinogenic PAH, yet the increased generation of nitrogen oxides enhances the formation of the carcinogenic N-nitrosamines, especially the TSNA in the smoke. However, all analytical measures of the smoke components have been established on the basis of standardized machine smoking conditions, such as those introduced by the Federal Trade Commission, that call for 1 puff to be taken once a minute over a 2-s period with a volume of 35 ml. These smoking parameters may have simulated the way in which people used to smoke the high-yield cigarettes; however, they no longer reflect the parameters applicable to contemporary smokers, and especially not those applicable to the smoking of low- and ultra-low-yield filter cigarettes. Recent smoking assays have demonstrated that most smokers of cigarettes with low nicotine yield take between 2 and 4 puffs per minute with volumes up to 55 ml to satisfy their demands for nicotine. The overview also discusses further needs for reducing the toxicity and carcinogenicity of cigarette smoke. From a public health perspective, nicotine in the smoke needs to be lowered to a level at which there is no induction of dependence on tobacco.
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PMID:The changing cigarette, 1950-1995. 912 Aug 72

Nitric oxide (NO) exerts pleiotroptic anti-atherosclerotic effects in the vascular wall: vasodilation, inhibition of platelet aggregation, elukocyte adhesion, and smooth muscle cell proliferation. Experimental and clinical studies showed that the biological effects of NO are impaired in patients with peripheral arterial occlusive disease. In a cross over study with 77 PAOD patients, we could demonstrate impaired NO formation by measuring the index metabolites of NO, nitrate and cyclic GMP. One possible mechanism of these pathophysiological changes is accumulation of the endogenous inhibitor of NO synthesis, asymmetrical dimethylarginine (ADMA). The NO-mediated functions of the vascular endothelium will become increasingly important in the clinic: diagnostically, measuring endothelium-dependent vasodilation may become a risk indicator for the development or progression of cardiovascular disease and for assessing the effects of antiatherosclerotic therapy; therapeutically, treatment strategies will be developed aiming at improving endothelial function. In early clinical studies, administration of L-arginine, the amino acid precursor of endogenous NO, has resulted in increased NO formation rates, which may prove therapeutically effective in the future.
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PMID:[Endothelial dysfunction in peripheral arterial occlusive disease: from basic research to clinical use]. 938 83

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Its concentration is elevated in patients with end-stage renal disease (ESRD), in part because it is excreted via the kidneys. In this study, the plasma concentrations of ADMA, symmetric dimethylarginine, and L-arginine were determined in relation to plasma nitrate levels (as an index of NO formation) for a group of 80 patients with ESRD. The effects of two treatment methods, i.e., hemodialysis (HD) and peritoneal dialysis (PD), and the role of the presence of atherosclerotic disease were evaluated. Forty-three patients receiving HD and 37 patients receiving PD were compared with healthy control subjects. Plasma L-arginine and dimethylarginine levels were determined by HPLC, using precolumn derivatization with o-phthaldialdehyde. Plasma nitrate levels were determined by gas chromatography-mass spectrometry. Predialysis ADMA concentrations in HD-treated patients were approximately sixfold higher than those in the control group (6.0+/-0.5 versus 1.0+/-0.1 micromol/L; P < 0.05). Plasma nitrate concentrations were significantly lower in HD-treated patients, which suggests that ADMA may inhibit NO synthase. In contrast, plasma ADMA levels and nitrate concentrations in PD-treated patients were similar to those in control subjects. Plasma L-arginine concentrations were not significantly decreased in patients with ESRD. ADMA concentrations were significantly decreased 5 h after HD, compared with baseline values. ADMA levels were significantly higher in HD-treated patients with manifest atherosclerotic disease than in HD-treated patients without atherosclerotic disease (7.31+/-0.70 versus 3.95+/-0.52 micromol/L; P < 0.05). This study confirms that ADMA is accumulated in ESRD. PD-treated patients exhibit significantly lower ADMA levels than do HD-treated patients. Accumulation of ADMA may be a risk factor for the development of endothelial dysfunction and cardiovascular disease in patients with ESRD.
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PMID:Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: relationship to treatment method and atherosclerotic disease. 1007 10

Erectile dysfunction is a common condition in men with cardiovascular disease, probably as a result of shared factors that impair hemodynamic mechanisms in the penile and ischemic vasculature. Sildenafil citrate, an orally active, selective inhibitor of phosphodiesterase type 5 (PDE5), has demonstrated excellent efficacy and safety profiles in men with erectile dysfunction of various etiologies. Sildenafil administration is contraindicated in patients who are taking nitrates or nitric oxide donors. This retrospective subanalysis of data from double-blind, placebo-controlled studies assessed the efficacy (9 studies) and safety (11 studies) of sildenafil in patients with erectile dysfunction and ischemic heart disease who were not taking nitrates. Of 3,672 patients randomized to receive sildenafil (5-200 mg) or placebo for 4-24 weeks in 11 double-blind, placebo-controlled studies, 357 (10%) reported a history (past or present) of ischemic heart disease and were not taking nitrates. Efficacy was assessed using end-of-treatment responses to Question 3 (ability to achieve an erection) and Question 4 (ability to maintain an erection) of the International Index of Erectile Function (IIEF), scores for the 5 domains of male sexual function assessed by the IIEF (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), and responses to a global efficacy question ("Did the treatment improve your erections?"). The responses to the 2 IIEF questions were graded on a scale of 1 (almost never or never) to 5 (almost always or always), with a score of 0 indicating no attempt at sexual intercourse. At the end of treatment, the mean scores for Question 3 and Question 4 of the IIEF for patients with erectile dysfunction and ischemic heart disease were significantly higher for the sildenafil group than for the placebo group (p <0.0001). Mean end-of-treatment scores for the IIEF domains also demonstrated significant increases for sildenafil-treated patients compared with those receiving placebo (p <0.05). At the end of treatment, improved erections were reported by 70% of patients who received sildenafil and by 20% of those in the placebo group p <0.0001). For the sildenafil group, the incidences of the most common adverse events (headache 25%, flushing 14%, and dyspepsia 12%) for patients with ischemic heart disease were similar to those in patients without this concomitant illness (21%, 15%, and 10%, respectively). Moreover, the overall incidence of cardiovascular adverse events other than flushing was comparable in patients with and without ischemic heart disease for both treatment groups. Since there is a degree of cardiac risk associated with sexual activity, clinicians should consider the patient's cardiovascular status before initiating any treatment for erectile dysfunction. Physicians should be aware that patients with underlying cardiovascular disease could be adversely affected by the vasodilator effects of sildenafil, especially in combination with sexual activity. The results of the present subanalysis indicate that oral sildenafil significantly improves erectile function and is well tolerated in patients with erectile dysfunction and ischemic heart disease who are not taking nitrate therapy.
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PMID:Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease. 1007 40

Sildenafil citrate is the first orally active therapy proved to be effective and safe treatment for erectile dysfunction (ED). Because men with cardiovascular disease are at increased risk of developing ED, and because ED and cardiovascular disease share important risk factors, attention has focused recently on the use of sildenafil in these men. When used in combination with nitroglycerin and other nitric oxide (NO) donors, sildenafil may potentiate major drops in blood pressure. Use of nitrate antianginal agents are an absolute contraindication to sildenafil use. In normotensive men and in men receiving antihypertensive medications evaluated in Phase II/III clinical trials, sildenafil use at the recommended doses (25-100 mg 1 hour before sexual intercourse and no more than once daily) was associated with modest, transient reductions in blood pressure and negligible effects on heart rate. In a more recent study, sildenafil was well tolerated in patients receiving antihypertensive medications and was not associated with major decreases in blood pressure. From the time of its approval in the United States in March 1998 through mid-November 1998, with approximately 6 million prescriptions written, 130 deaths were reported by the US Food and Drug Administration (FDA). Seventy-seven of the men who died had documented cardiovascular events. Sixteen men took or were administered nitroglycerin or an organic nitrate; 3 others had nitroglycerin in their possession. Physician prescribing guidelines issued by the American College of Cardiology/American Heart Association (ACC/AHA) recommend caution when prescribing sildenafil to men with certain cardiovascular conditions, liver or kidney disease, and to those taking medications that may prolong sildenafil's half-life (e.g., erythromycin or cimetidine). Those with known or suspected coronary artery disease may benefit from an exercise test to determine whether resumption of sexual activity with use of sildenafil is likely to be associated with an increased risk of myocardial ischemia.
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PMID:Cardiovascular effects of sildenafil citrate and recommendations for its use. 1050 71

There is a large body of literature describing the causative role of oxidative stress mediated by increased levels of reactive oxygen species in the pathogenesis of cardiovascular disease such as atherosclerosis, hypertension, and restenosis after angioplasty. The positioning of a soft silicone collar around the rabbit carotid artery elicits intimal thickening. The findings from recent studies demonstrated that both intimal thickening and atherosclerosis lead to synthesis of inducible nitric oxide synthase, resulting in abundant amounts of nitric oxide. We investigated the effects of collaring and nicardipine treatment on the activities of antioxidant enzymes, superoxide dismutase and catalase, and total nitrite/nitrate levels, stable products of nitric oxide. Placing the collar increased the total nitrite/ nitrate levels and decreased superoxide dismutase activity in collared arteries. Treatment with nicardipine (20 mg/kg/day, s.c.) prevented enhanced nitric oxide degradation without affecting superoxide dismutase and catalase activities. Our results suggest that enhanced nitric oxide production and superoxide anion are generated in response to the collaring, resulting in oxidative stress within the segment in this model.
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PMID:Antioxidant enzyme activities and total nitrite/nitrate levels in the collar model. Effect of nicardipine. 1077 57

Elevated urinary albumin excretion (UAE) is a predictor of cardiovascular disease, and one possible explanation is that elevated UAE reflects a generalized vascular dysfunction. The present study tests whether the plasma concentrations of the two main endothelial vasoactive substances (nitric oxide and endothelin-1 [ET-1]) are changed in clinically healthy subjects with elevated UAE (>6.6 microg/ min-the 90th percentile in the background population) and to test associations between these concentrations and systemic blood pressure. Twenty-seven subjects with elevated UAE were compared with 46 matched controls with normoalbuminuria. Plasma concentration of ET-1 was measured using an ELISA method and plasma concentration of nitrate/nitrite using a photometric method. Twenty-four-hour blood pressure was measured using a portable recorder (TM-2421). No significant differences in the concentrations of nitrate/nitrite and ET-1 were found between the groups, e.g. 21 (10-105) vs. 18 (11 -152) (p=0.33) and 0.98 (0.58 1.95) vs. 1.10 (0.54 -1.50) (p = 0.27), respectively. However, plasma nitrate/nitrite was significantly positively correlated to systolic and diastolic blood pressure in subjects with normoalbuminuria but not in subjects with elevated UAE. In contrast, plasma ET-1 concentration was significantly positively correlated to systolic blood pressure only in subjects with elevated UAE. In conclusion, elevated UAE is not associated with changed plasma concentrations of endothelial vasoactive substances in clinically healthy subjects. However, nitrate/nitrite is positively correlated to BP only in subjects with normoalbuminuria, and ET-1 is positively correlated to BP only in subjects with elevated UAE.
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PMID:Plasma concentrations of endothelial vasoactive substances in clinically healthy subjects. associations with urinary albumin excretion and ambulatory blood pressure. 1081

Experimental studies investigating the effects of exercise on plasma total homocyst(e)ine (H[e]) levels in humans are almost non-existent. H(e) has been demonstrated to represent an independent risk factor for cardiovascular disease. The exact mechanism through which H(e) exerts its effects on the arteries is unknown but it is thought to involve nitric oxide (NO). The present study was designed to assess the effects of acute submaximal exercise on H(e) while levels of NO inhalation were manipulated using an air-filter mask. The study was completed by seven male volunteers, aged 21.6+/-1.3 yr (X+/-SD), VO2max: 48.6+/-7.6 mL x kg(-1) x min(-1). During two separate occasions the subjects performed a 1-hour bout of submaximal exercise on a stationary cycle ergometer at 60% of their VO2max. The two trials were completed in random order (with and without mask). Data were collected before (PRE) and after (POST) the acute exercise bouts. Plasma H(e) was directly measured by HPLC and NO by quantifying the enzymatic oxidation to nitrite (NO2-) & nitrate (NO3-). Mean H(e) concentrations were 10.89+/-2.05 nmol/mL (PRE) & 11.21+/-1.81 nmol/mL (POST) and were not significantly altered by submaximal exercise. When wearing a mask, the correlation of the PRE/POST H(e) differences with the PRE/ POST differences in NO3- were 0.77 (P=0.07). No correlation was found between either H(e) and NO2- or between NO2- and NO3-. However, a significant correlation (r= - 0.86, P= 0.03) was also observed between H(e) and NO2- but only for the post-exercise values when wearing a mask. The results suggest that: (1) plasma H(e) levels are not affected by acute submaximal exercise; (2) there is insufficient evidence to support the view that plasma H(e) levels are being mediated by NO during either rest or exercise.
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PMID:Interactions between homocyst(e)ine and nitric oxide during acute submaximal exercise in adult males. 1085 96

Diabetes is associated with endothelial dysfunction and increased risk of hypertension, cardiovascular disease, and renal complications. Earlier studies have revealed that hyperglycemia impairs nitric oxide (NO) production and diabetes causes endothelial dysfunction in humans and experimental animals. This study was designed to test the effects of altered concentrations of glucose, insulin, and glucagon, the principal variables in types I and II diabetes, on NO production and endothelial NO synthase (eNOS) expression in cultured human coronary endothelial cells. Cultured endothelial cells were incubated in the presence of glucose at either normal (5.6 mM) or high (25 mM) concentrations for 7 days. The rates of basal and bradykinin-stimulated NO production (nitrate + nitrite) and eNOS protein expression (Western blot) were then determined at the basal condition and in the presence of insulin (10(-8) and 10(-7) M), glucagon (10(-8) and 10(-7) M), or both. Incubation with a high-glucose concentration for 7 days significantly downregulated, whereas insulin significantly upregulated, basal and bradykinin-stimulated NO production and eNOS expression in cultured endothelial cells. The stimulatory action of insulin was mitigated by high-glucose concentration and abolished by cotreatment of cells with glucagon. Thus hyperglycemia, insulinopenia, and hyperglucagonemia, which frequently coexist in diabetes, can work in concert to suppress NO production by human coronary artery endothelial cells.
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PMID:Effects of simulated hyperglycemia, insulin, and glucagon on endothelial nitric oxide synthase expression. 1089 17

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