Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SIN 1, the bioactive metabolite of molsidomine, not only appears to lack the problem of inducing nitrate tolerance, but also exerts antiaggregatory and fibrinolytic properties. These effects, which either are not or only in part shared by the drug isosorbide-5-mononitrate, might be beneficial in the prevention of thromboembolic complications in cardiovascular disease. In contrast to the effects of acetylsalicylic acid, SIN 1 already inhibits aggregation during the first phase of aggregation, and it inhibits aggregations induced by agonists that are not or only marginally influenced by acetylsalicylic acid (such as the aggregation induced by platelet activating factor). Thus, the antiaggregatory effects of molsidomine cannot replace the effects of acetylsalicylic acid, while a combination of both drugs might be of benefit in the treatment of patients with cardiovascular disease.
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PMID:[Platelet aggregation with SIN 1: comparison with isosorbide-5-mononitrate and acetylsalicylic acid]. 177 39

Nitrates are among the most widely prescribed drugs in cardiovascular disease. They are able to prevent and to interrupt episodes of myocardial ischaemia, alleviate anginal symptoms, and exert favourable effects in acute myocardial infarction and in congestive heart failure. Most of these effects can be explained by their ability to relax smooth muscle cells: peripheral vasodilation, in veins and in arteries, reduces cardiac workload, thereby decreasing oxygen consumption; furthermore, nitrates dilate coronary arteries directly, thereby increasing myocardial oxygen supply. However, nitrates also exert effects on blood platelets. These occur by the same mechanisms operating on blood vessels, a stimulation of soluble guanylate cyclase and a consequent increase in cytosolic levels of cyclic GMP. When added to platelet suspensions nitrates inhibit platelet aggregation by almost all known stimuli. Such effects in vitro generally require high concentrations of drugs; evidence has been obtained, however, that nitrates may inhibit platelet function also in vivo. Such evidence derives from ex vivo studies with platelet aggregometry, from experiments showing the synergism of nitrates and prostacyclin and the requirement for nitrate action of sulphydryl group donors such as N-acetyl-cysteine, and from studies on bleeding time. Antiplatelet effects of nitrates may be an explanation for the protection from death and reinfarction, inferred on the basis of meta-analysis of several studies in acute myocardial infarction.
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PMID:[Antiplatelet effects of nitrate derivatives]. 193 57

Water-suppressed proton nuclear magnetic resonance (NMR) of plasma was proposed as a technique for detecting malignant tumors. In that analysis, bloods drawn from cancer patients at the Beth Israel Hospital (BIH; Boston, MA), were easily distinguished from normal subjects by measuring and averaging the proton NMR methyl and methylene line widths of plasma lipoproteins. We collected blood at the Massachusetts General Hospital (MGH), including from normal controls, patients with untreated and treated malignant tumors, and patients with nontumor diseases. The plasma NMR analyses were carried out blind. The code was not broken until all patient charts and pathology records were reviewed, plasma analyses were completed, and patients had been divided into appropriate clinical groups. Analysis of these data showed no differences between the means of the study groups (false-positive and false-negative frequencies 46% and 57%, respectively). An inverse correlation of methyl/methylene line widths with age (P less than .01), and a correlation with nitrate-requiring cardiovascular disease (P less than .05) was, however, evident. This test cannot be validly used to detect malignancy.
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PMID:Failure of 1H nuclear magnetic resonance spectroscopy of blood plasma to detect malignancy. 233 73

Nitrates are potent relaxers of vascular smooth muscle and act by dilating veins, arteries, and arterioles (especially at high doses). Their clinical effects have been considered to be dominantly related to peripheral actions: systemic venodilatation and a decrease in systemic vascular resistance, reducing the preload and afterload of the heart. Considerable experimental work confirms potent salutary effects on the coronary circulation. These drugs are readily absorbed across mucosal surfaces; they are available in multiple formulations, including sublingual, buccal, oral, and topical delivery systems. Nitrate administration should begin with low doses and increased to doses that are often higher than previously recommended until a specific clinical end point or limiting side effects occur. Organic nitrate esters are effective in the treatment of stable angina pectoris, unstable angina, coronary vasospastic syndromes, and in vasodilator therapy in severe congestive heart failure. The pathophysiology of these syndromes is reviewed with respect to the clinical actions of nitrates on the central and peripheral circulations. The side effects of nitrates include headache, dizziness, and nausea. Nitrate tolerance, a controversial subject, does not appear to be an important clinical problem. Using the guidelines presented in this review, nitrate therapy provides effective, inexpensive, well-tolerated therapy for many patients with cardiovascular disease.
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PMID:Nitroglycerin and long-acting nitrates in clinical practice. 640 16

Postmenopausal women (PMW) have an increased risk of cardiovascular disease that is attenuated by hormone replacement therapy (HRT). Inasmuch as hypertension and atherosclerosis are associated with diminished endothelium-derived nitric oxide (NO), we investigated whether HRT augments NO release in PMW. We determined serum levels of nitrite/nitrate (NO2 + NO3) at baseline and during the 6th, 12th, and 24th months of the study in two groups of PMW. One group (HRT-PMW, n = 13) received continuous transdermal administration of 17 beta-estradiol (Estraderm-TTS-50) supplemented with oral norethisterone acetate (NETA) on days 1 through 12 of each month, and the other group (control PMW, n = 13) did not receive HRT. Blood samples in the HRT-PMW group were collected without regard to whether subjects were taking NETA at the time of blood sampling. Serum NO2 + NO3 levels increased in HRT-PMW for the duration of the study, whereas serum NO2 + NO3 levels remained unchanged in control PMW. When all samples regardless of timing of collection with respect to NETA treatment were included in the statistical analysis, the change in NO2 + NO3 levels in HRT-PMW was significantly greater compared with the change in control PMW (P = .037). Likewise, when only those samples collected when estradiol-treated subjects were not taking oral NETA were included in the statistical analysis, the change in NO2 + NO3 levels in the HRT-PMW group remained significant (P = .047) compared with control PMW.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol and norethisterone acetate. A two-year follow-up study. 772 43

Ovarian dysfunction as well as impaired release of endothelium-derived nitric oxide (NO) is associated with increased incidence of cardiovascular disease in postmenopausal women. Estrogen replacement therapy in postmenopausal women has a cardioprotective effect. Hence, using follicular development (FD) phase of the menstrual cycle of normal women (n = 7) and of patients undergoing in vitro fertilization (n = 16), we tested whether ovarian/sex hormones modulate NO-release. Levels of nitrite/nitrate (stable metabolites of NO), 17 beta-estradiol (E), progesterone (P), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured in serum collected during FD-phase. Serum nitrite/nitrate levels increased (p < .01) with the normal, as well as hormonally-induced FD and correlated with increases in serum E levels (r2 = 0.67; p < .01), but not with P, FSH and LH (p > .05). Post-ovulatory increase in P and LH levels decreased serum nitrite/nitrate levels (p < .05), even in presence of high E levels. In conclusion, nitrite/nitrate increase with follicular development, an effect that is potentially mediated by E induced NO release.
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PMID:Circulating nitrite/nitrate levels increase with follicular development: indirect evidence for estradiol mediated NO release. 806 Mar 38

Nitric oxide (NO) is generally considered as an endogenous vasoprotective agent. Various studies indicate that the female sex hormone estradiol, that contributes to the well known gender differences in cardiovascular disease, may enhance NO-production. Thus we studied sex differences in NO-generation by measuring single breath NO-exhalation and plasma levels of nitrate (NO3), the stable endmetabolite of NO. In this observational trial 22 male and 21 female volunteers, 19 to 38 years of age, were studied on 3 days at weekly intervals. Median concentrations of NO were 20 parts per billion (95% CI: 16 to 32 ppb) in women and 34 ppb (95% CI: 31 to 58 ppb) in men. The median plasma concentrations of NO3 were 14 microM/L (95% CI: 11 to 23 microM/L) in women and 27 microM/L (95% CI: 24 to 47 microM/L) in men. Thus, men exhaled 59% more NO (p < 0.001) and had 99% higher NO3 levels than women (p < 0.0001). Even when exhaled NO concentrations were corrected for body weight, men exhaled 50% more NO than women (p = 0.024). No significant changes in measured endpoints were seen during the menstrual cycle (p > 0.05) in women. In view of the diversity of NO-actions, the finding of marked sex differences in NO-production is basic to the elucidation of gender differences in a number of (patho)-physiologic conditions.
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PMID:Sex differences in concentrations of exhaled nitric oxide and plasma nitrate. 856 19

The incidence of cigarette smoking tends to be higher in women, justifying directed studies on smoke-related mechanisms of cardiovascular disorder in females. Platelet activity plays an important etiological role in several settings of cardiovascular disease. Cigarette smoking facilitates platelet formation of proaggregatory thromboxane A2. However, cigarette smoke contains nitric oxide (NO), which has antiplatelet activity. Furthermore, the formation of anti-aggregatory prostacyclin (PGI2) may be higher in smokers than in non-smokers. Hence, the concerted action of NO and PGI2 on platelet activity in smoking females is important to elucidate. The metabolites of TxA2, NO, and PGI2, as well as cyclic guanosine 3':5'-monophosphate (cGMP; second messenger for NO in the platelets) and cyclic adenosine 3':5'-monophosphate (cAMP; second messenger for PGI2 in the platelets), were analysed in 23 healthy female smokers (daily consumption 11-20 cigarettes per day) and in 26 matched non-smokers. The urinary excretion of 2,3-dinor TxB2 (metabolite of TxA2) was considerably higher in smokers than in non-smokers (177 vs. 72 pg/mg creatinine, respectively; P<0.001). Plasma and urinary levels of nitrate (metabolite of inhaled NO) did not differ between the groups. Plasma and urinary cGMP were slightly increased (252 vs. 193 nmol/L; P<0.05 and 0.63 vs. 0.51 micromol/24 h; P<0.05, respectively) in smokers compared to non-smokers, while platelet cGMP was lower in smokers than in non-smokers (81 vs. 10.3 pmol/10(6) platelets, respectively; P<0.05). The urinary excretion of 2,3-dinor-6-keto-PGF1a (metabolite of PGI2) did not differ between the groups. Platelet or urinary cAMP did not differ between the groups either, while plasma cAMP was lower in smokers than in non-smokers (19.2 vs. 26.2 nmol/l, respectively; P<0.001). In healthy female smokers NO is not absorbed from the inhaled smoke, and endothelial PGI2 formation is not enhanced to counterbalance the increased platelet formation of proaggregatory TxA2.
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PMID:Smoke-derived nitric oxide and vascular prostacyclin are unable to counteract the platelet effect of increased thromboxane formation in healthy female smokers. 873 16

Endothelial dysfunction based on lack of nitric oxide (NO) may contribute to several settings of cardiovascular disorder. Chronic oral supplementation with the NO precursor L-arginine counteracts the development of aortic atherosclerosis in cholesterol-fed rabbits, and i.v. infusion of L-arginine may acutely improve endothelium-dependent coronary epicardial vasodilation in patients with hypercholesterolemia (HC). To clarify whether excess NO precursor may also improve general cardiovascular performance in HC, we measured working capacity indices of myocardial ischemia, and basal and post-occlusive forearm and skin blood flow in nine patients with elevated plasma cholesterol (9.1 +/- 0.2 mumol/l) following random double-blinded administration of L-arginine (16 g i.v.) or placebo. Infusion of L-arginine raised the plasma concentration of this amino acid from 85 +/- 12 to 2460 +/- 230 mumol/l but did not change the plasma level of the major NO metabolite nitrate. Maximal working capacity, indices of myocardial ischemia, and basal and post-occlusive blood flow in the skin or forearm did not differ between the treatments. The lack of positive effect of L-arginine compared to placebo indicates that excess NO precursor did not improve microvascular endothelial function in the patients, or alternatively, that the indices measured in the present study were not dependent on endothelial microvessel function. Thus, in patients with HC, deficiency of precursor for NO formation does not seem to impair either maximal exercise capacity myocardial perfusion during maximal exercise, or maximal vasodilator capacity in skeletal muscle or skin.
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PMID:Acute supplementation with the nitric oxide precursor L-arginine does not improve cardiovascular performance in patients with hypercholesterolemia. 877 Mar 16

Increased incidence of cardiovascular disease in postmenopausal women (PMW) is accompanied by ovarian dysfunction; hormone replacement therapy (HRT) can have cardioprotective effects. Because hypertension and atherosclerosis are associated with impaired release of endothelium-derived nitric oxide (NO) and increased levels of low-density lipoproteins (LDL), we investigated whether HRT augments NO release, and whether these increases are accompanied by a decrease in LDL levels in PMW. We determined serum nitrite/ nitrate (NO2-/NO3-) and LDL levels at baseline (before initiation of HRT) and during the 6th and 12th months of the study. The PMW (n = 26) received continuous oral administration of estradiol valerate (Progynova, 2 mg daily) for 21 days supplemented with either oral cyproterone acetate (CPA; 1 mg; n = 11) or medroxyprogesterone acetate (MPA; 5 mg; n = 15) on days 12-21 of each treatment cycle. Blood samples in the PMW receiving HRT were collected at times while the subjects were taking estradiol valerate alone and estradiol valerate plus CPA or MPA. Compared with the samples collected at baseline, serum NO2-/NO3- levels increased significantly from 20.1 +/- 1.58 mumol/L at baseline to 30 +/- 3.7 mumol/L (P < 0.01) in samples collected after 12 months of HRT while the PMW were not taking progestins (CPA or MPA), and to 25.4 +/- 2 mumol/L (P < 0.05) when all the samples, regardless of the treatment with CPA or MPA, were included in the analysis. Moreover, > 30% increase in serum NO2-/NO3- levels were observed only in 13 (responders) out of 26 PMW substituted with estradiol valerate, suggesting that estradiol may improve endogenous NO synthesis in a differential fashion. Compared with baseline, no significant increases in serum NO2-/NO3- were observed in samples collected while the estradiol-treated responders were taking either CPA or MPA. In contrast to NO2-/NO3- serum LDL levels were significantly reduced in samples collected after 12 months of HRT (P < 0.05 vs. baseline). Furthermore, levels of NO2-/NO3 showed a significant negative correlation with the levels of LDL (r2 = 0.17; P < 0.05) in the responders but not in nonresponders. These results indicate that oral administration of estradiol valerate in PMW for HRT increases circulating NO levels, an effect that may contribute to the cardioprotective effects of HRT in PMW. In addition, our data suggests but does not prove that concomitant administration of a progestin may attenuate the beneficial effects of estrogen replacement therapy with regard to NO release. Finally, our data provides evidence for the existence of responders and nonresponders to postmenopausal estrogen treatment with respect to improvement of endogenous NO levels, suggesting that a significant number, but not all, of the hormonally substituted PMW profit fully from the beneficial properties of a HRT.
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PMID:Differential effects of hormone-replacement therapy on endogenous nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol valerate and cyproterone acetate or medroxyprogesterone acetate. 902 24


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