Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocarditis is thought to be commonly caused by various viruses, and accumulating evidence links viral myocarditis with the eventual development of dilated cardiomyopathy. Heart disease is the most prevalent cause of morbidity and mortality in developed countries. Cytokines are being increasingly recognized as an important factor in the pathogenesis of myocarditis and cardiomyopathy. Elevated levels of circulating cytokines have been reported in patients with heart failure, and various cytokines have been shown to depress myocardial contractility in vitro and in vivo. A number of reports have shown that cytokines generated by activated immune cells cause an increase in nitric oxide (NO) via induction of NO synthase. Increased generation of NO may induce myocardial damage. It has been suggested that NO can be either beneficial or harmful to the host, NO can protect the myocardium against damage from CVB3 infection by inhibiting viral replication. A better molecular understanding of the direct effect of viral infection on cardiac myocytes and the balance of beneficial and detrimental effects of the immune response will ultimately provide insight into the mechanisms by which viral infections cause cardiomyopathy in humans.
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PMID:[Involvement of immune system in the pathogenesis of viral myocarditis]. 1200 27

1. This study examined whether NO is involved in the in-vivo coronary vasodilator effects of amlodipine (a calcium channel blocker) and whether heart failure (HF) alters the coronary responses to amlodipine. 2. Nine conscious dogs were chronically instrumented to measure circumflex coronary blood flow (CBF) and coronary diameter (CD). Drugs were administered directly into the circumflex artery through an indwelling catheter to avoid systemic changes. HF was induced by right ventricular pacing (240 b.p.m., 3 weeks). 3. Compared with control (C), in HF, coronary responses to acetylcholine (1 - 10 ng kg(-1)) were reduced while responses to nitroglycerin (0.1 - 0.5 microg kg(-1)) were unchanged. In C, amlodipine (30 - 150 microg kg(-1)), increased dose-dependently CBF and CD. After LNA (a NO synthase inhibitor, 2 mg kg(-1)), amlodipine produced less increases in CBF and CD (+121+/-26 ml min(-1) and +76+/-35 microm versus +196+/-40 ml min(-1) and +153+/-39 microm respectively for 150 microg kg(-1) amlodipine alone, both P<0.05). In HF, the coronary responses to amlodipine were reduced (150 microg kg(-1) of amlodipine increased CBF and CD +121+/-23 ml min(-1) and +77+/-21 microm respectively, both P<0.05). After LNA, the CBF responses to amlodipine tended to be reduced (+94+/-19 ml min(-1) at 150 microg kg(-1)) but CD responses were significantly reduced (+41+/-16 microm, P<0.05). The supplementation with L-arginine did not enhance the coronary responses to amlodipine. 4. These results indicate that, in conscious dogs, NO participates in the coronary responses to amlodipine and in HF, the coronary responses to amlodipine are reduced, which is related to a reduced NO production.
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PMID:Reduced coronary vasodilator responses to amlodipine in pacing-induced heart failure in conscious dogs: role of nitric oxide. 1201 Jul 75

Both systolic and diastolic cardiac dysfunction coexist in various degrees in the majority of patients with heart failure. Although ACE inhibitors are useful in the treatment of heart failure, the roles of bradykinin in the systolic and diastolic properties of left ventricular function under long-term treatment of ACE inhibitor have not been fully elucidated. We therefore evaluated the changes in left ventricular function, histomorphometry, and the expression of several failing heart related genes, by use of an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg per day), with an ACE inhibitor, enalapril (1 mg/kg per day), in dogs with tachycardia-induced heart failure (270 ppm, 22 days) and compared the effects to enalapril alone. Although there were no differences observed in blood pressure, left ventricular dimension, and percentage of fractional shortening, FR173657 significantly increased left ventricular filling pressure (P<0.01), prolonged the time constant of relaxation (P<0.05), and suppressed the expression of endothelial NO synthase and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (P<0.05). FR173657 also upregulated collagen type I and III mRNA (P<0.05) and increased the total amount of cardiac collagen deposits (P<0.05) in left ventricle compared with that in the enalapril-treated group. In conclusion, endogenous bradykinin contributes to the cardioprotective effect of ACE inhibitor, improving left ventricular diastolic dysfunction rather than systolic dysfunction, via modification of NO release and Ca(2+) handling and suppression of collagen accumulation.
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PMID:Bradykinin improves left ventricular diastolic function under long-term angiotensin-converting enzyme inhibition in heart failure. 1201 75

Endothelial dysfunction (ED) has been documented in patients with both coronary artery disease (CAD) and chronic heart failure (CHF)-being responsible for exercise-induced myocardial ischemia in the former and increased afterload in the latter. In the last two decades exercise training has assumed a major role in both cardiovascular disorders. In CAD exercise training has established positive effects on myocardial perfusion. Recently, exercise training has been shown to attenuate paradoxical vasoconstriction in CAD. The improved ED after training explains the improvement of myocardial perfusion in the absence of changes in baseline coronary artery diameter. Since ED has been identified as a predictor of coronary events exercise may contribute to long-term reductions of cardiovascular mortality. In CHF the increased peripheral vascular resistance - especially during exercise - is more important. ED contributes to the peripheral vasoconstriction. Training programs have shown to improve ED in CHF. A long-term study of hemodynamic effects of training in CHF revealed a significant reduction of total peripheral resistance (TPR) that after 6 months with a concomitant increase in stroke volume. In a subgroup analysis a significant correlation between changes in TPR and changes in peripheral ED was observed. Cell culture and animal experiments suggest that shear stress increases the endothelial L-arginine uptake, enhances NO synthase activity and expression, and upregulates the production of extracellular superoxide dismutase, which prevents premature NO breakdown. All these molecular effects converge on a reduction of myocardial ischemic events in CAD and a decrease of afterload in CHF.
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PMID:Exercise training and endothelial dysfunction in coronary artery disease and chronic heart failure. From molecular biology to clinical benefits. 1203 63

Strong expression of the inducible form of nitric oxide synthase (NOS II) has been shown in the myocardium of patients with myocardial infarction (MI). We hypothesized that NOS II plays an important role in the development of MI and subsequent heart failure and that inhibition of NOS II may beneficially alter the course of the disease. Long-term administration (2 mo) of the selective NOS II inhibitor S-methylisothiourea (SMT) to rats with MI significantly improved cardiac function. A significant drop in mortality, lung water content, infarct size, and cardiomyocyte hypertrophy was also associated with the use of SMT. Plasma concentration of nitrite and nitrate was also reduced by SMT. Short-term administration of SMT (first 2 wk only) significantly reduced infarct size; however, it did not improve cardiac dysfunction measured 2 mo after MI. These findings demonstrate that induction of NOS II during MI exerts negative effects on cardiac function and structure. Long-term administration of a selective NOS II inhibitor may prove to be beneficial in the treatment of MI and congestive heart failure.
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PMID:Inhibition of NOS II prevents cardiac dysfunction in myocardial infarction and congestive heart failure. 1206 7

The advent of recombinant technology has revealed attractive therapeutic profile of insulin-like growth factor I (IGF-1) in the treatment of chronic cardiovascular diseases such as diabetes and heart failure. However, the safety and potential adverse effect of IGF-1 have not been well defined. This study was designed to evaluate the impact of short-term IGF-1 administration on myocardial contractile function. Adult rats were given recombinant human IGF-1 (3mg/kg/d, s.c.) for 8 weeks. Mechanical properties were evaluated in left-ventricular papillary muscles using a force-transducer. Myocardial contractile properties analyzed included peak tension development (PTD), time-to-peak tension (TPT), time-to-90% relaxation (RT(90)), and maximal velocity of tension development/decline (+/-VT). Short-term IGF-1 treatment enhanced the plasma IGF-1 level but had no effect on body and organ weights. The myocardium from IGF-1-treated rats exhibited enhanced PTD associated with similar TPT, RT(90), and +/-VT compared to the control group. IGF-1-treated myocardium exhibits an enhanced PTD-Ca(2+) response and a better intracellular Ca(2+) replenishing ability at the low stimulus frequencies. Acute application of IGF-1 (1-500 ng/ml) elicited a comparable concentration-dependent increase in PTD in myocardium from both control and the IGF-1-treated groups. Acute IGF-1 application had no effect on +/-VT, TPT, and RT(90) in either group tested. Pretreatment with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester blunted the IGF-1-induced positive response in myocardium from both control and IGF-1-treated groups. These results suggest that short-term IGF-1 treatment is unlikely to induce IGF-1 resistance in myocardial contractile function.
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PMID:Short-term administration of insulin-like growth factor I (IGF-1) does not induce myocardial IGF-1 resistance. 1216 97

Cardiac hypertrophy occurs in pathological conditions associated with chronic increases in hemodynamic load. Although hypertrophy can initially be viewed as a salutary response, ultimately, it often enters a phase of pathological remodeling that may lead to heart failure and premature death. A prevailing concept predicts that changes in gene expression in hypertrophied cardiac myocytes and cardiac myocyte loss by apoptosis contribute to the transition from hypertrophy to failure. In recent years, nitric oxide (NO) has emerged as an important regulator of cardiac remodeling. Specifically, NO has been recognized as a potent antihypertrophic and proapoptotic mediator in cultured cardiac myocytes. Studies in genetically engineered mice have extended these findings to the in vivo situation. It appears that low levels and transient release of NO by endothelial NO synthase exert beneficial effects on the remodeling process by reducing cardiac myocyte hypertrophy, cavity dilation and mortality. By contrast, high levels and sustained production of NO by inducible NO synthase seem to be maladaptive by reducing ventricular contractile function, and increasing cardiac myocyte apoptosis, and mortality. In the future, these novel insights into the role of NO in cardiac remodeling should allow the development of novel therapeutic strategies to treat cardiac remodeling and failure.
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PMID:Regulation of cardiac remodeling by nitric oxide: focus on cardiac myocyte hypertrophy and apoptosis. 1237 17

In many types of cardiovascular pathophysiology such as hypercholesterolemia and atherosclerosis, diabetes, cigarette smoking, or hypertension (with its sequelae stroke and heart failure) the expression of endothelial NO synthase (eNOS) is altered. Both up- and downregulation of eNOS have been observed, depending on the underlying disease. When eNOS is upregulated, the upregulation is often futile and goes along with a reduction in bioactive NO. This is due to an increased production of superoxide generated by NAD(P)H oxidase and by an uncoupled eNOS. A number of drugs with favorable effects on cardiovascular disease upregulate eNOS expression. The resulting increase in vascular NO production may contribute to their beneficial effects. These compounds include statins, angiotensin-converting enzyme inhibitors, AT1 receptor antagonists, calcium channel blockers, and some antioxidants. Other drugs such as glucocorticoids, whose administration is associated with cardiovascular side effects, downregulate eNOS expression. Stills others such as the immunosuppressants cyclosporine A and FK506/tacrolimus or erythropoietin have inconsistent effects on eNOS. Thus regulation of eNOS expression and activity contributes to the overall action of several classes of drugs, and the development of compounds that specifically upregulate this protective enzyme appears as a desirable target for drug development.
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PMID:Regulation of endothelial-type NO synthase expression in pathophysiology and in response to drugs. 1238 13

Recent epidemiological studies associate health effects and particulate matter in ambient air. Exacerbation of the particle-induced inflammation can be a mechanism responsible for increased hospitalization and death due to cardiopulmonary events in high-risk groups of the population. Systems regulating blood pressure that depend on lung integrity can be involved in progression of cardiovascular diseases. This study focused on the expression levels of various genes involved in cardiovascular and pulmonary diseases to assess their role in the onset of cardiovascular problems due to ambient particulate matter and compared these with the corresponding products. Rats with ozone-induced (1600 microg/m(3); 8 h) pulmonary inflammation were exposed to 0.5 mg, 1.5 mg, or 5 mg of particulate matter (PM) from Ottawa Canada (EHC-93) by intratracheal instillation. mRNA levels of various genes and their products were measured 2, 4, and 7 d after instillation. At 2 d after exposures to PM, tumor necrosis factor (TNF)-alpha levels in bronchoalveolar lavage fluid (BALF) were elevated approximately 4 times for the highest EHC-93 dose. MIP-2 protein levels in BALF were elevated approximately three times during the entire time period studied, whereas IL-6 levels were not affected compared to control groups. The MIP-2 mRNA levels revealed a similar pattern of induction. A twofold increase in endothelin (ET)-1 levels at d 2 and a 20% decrease in angiotensin-converting enzyme (ACE) activity at d 7 were measured in plasma. A 60% decrease of ACE and ET-1 mRNA levels suggested a possible endothelial damage in the lung blood vessels. Inducible nitric oxide synthase (iNOS) mRNA was found to be increased 3.5 times 2 d after instillation of the particles. Therefore, the endothelial damage could have been caused by large amounts of the free radical NO. Also, plasma levels of fibrinogen were elevated (20%), which could presumably increase blood viscosity, leading to decreased tissue blood flow. These changes in hematological and hemodynamic parameters observed in our study are in line with heart failure in high-risk groups of the population after high air pollution episodes.
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PMID:Health effects and time course of particulate matter on the cardiopulmonary system in rats with lung inflammation. 1239 69

Reactive oxygen species have an important pathogenic role in organ damage. We investigated the role of oxidative stress via nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the kidney of the Dahl salt-sensitive (DS) rats with heart failure (DSHF). Eleven-week-old DS rats fed an 8%-NaCl diet received either vehicle or imidapril (1 mg/kg per day) for 7 weeks. The renal expression of the NAD(P)H oxidase p47phox and endothelial NO synthase were evaluated. In DSHF rats, associated with increased renal angiotensin II, mRNA and protein expression of NAD(P)H oxidase p47phox were enhanced with an increase in renal lipid peroxidation production (0.33+/-0.03 versus 0.22+/-0.01 nmol/mg protein, P<0.05) and urinary excretion of hydrogen peroxide (26.9+/-6.6 versus 9.5+/-2.1 U/mg creatinine, P<0.01) compared with levels in Dahl salt-resistant rats. The endothelial NO synthase expression was decreased in the kidney. Treatment with imidapril reduced renal angiotensin II and NAD(P)H oxidase expression and the oxidative products (kidney lipid peroxidation product: 0.16+/-0.02, P<0.001; urinary hydrogen peroxide: 3.1+/-0.2, P<0.01 versus DSHF rats). Imidapril significantly decreased albuminuria and reduced glomerulosclerosis without changes in the blood pressure. In conclusion, DSHF rats showed increased oxidative stress in the kidney via NAD(P)H oxidase. Blockade of local angiotensin II with subpressor dose of imidapril inhibited NAD(P)H oxidase and prevented renal damage.
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PMID:Angiotensin II and oxidative stress in Dahl Salt-sensitive rat with heart failure. 1246 66


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