UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coordinated release of relaxing and contracting factors from the endothelium modulates arterial distensibility. Recently, a similar release of the same and other factors from the coronary endothelium was shown to modulate myocardial performance in humans. This paracrine modulation of left ventricular (LV) performance by substances released from the coronary endothelium mainly affects diastolic LV function. This was evident from the reduction in end-systolic LV pressure, the earlier onset of LV relaxation and the increased LV diastolic distensibility observed in normal subjects during bi-coronary infusion of substance P. In experimental preparations, substance P elicited similar effects on diastolic LV function, which were attributed to a paracrine myocardial action of nitric oxide (NO) because they were absent after addition of hemoglobin. In normal subjects, the myocardial effects of NO were investigated during bi-coronary infusion of the NO-donor sodium nitroprusside and resembled the effects observed during bi-coronary infusion of substance P. This paracrine control of diastolic LV function by the coronary endothelium is influenced by substrate availability and by many neurohumoral substances, whose plasma levels are raised in heart failure. In transplant recipients, bi-coronary co-infusion of substance P and of L-arginine, the substrate for NO production, potentiated the fall in LV filling pressures. Pretreatment with intravenous dobutamine augmented the drop in LV end-systolic pressures observed during bi-coronary infusion of substance P. In isolated papillary muscles, a higher baseline myocardial c-GMP level, as induced by atrial natriuretic peptide, potentiates the negative inotropic and relaxation hastening effects of NO. In isolated ejecting guinea-pig hearts, an endothelin receptor antagonist improved diastolic LV function and this improvement implies paracrine myocardial action on diastolic LV function not only of NO but also of endothelin. Coronary endothelial control of myocardial function affects LV performance both acutely and chronically. An acute increase in heart rate augments release of NO because of coronary reactive hyperemia, lowers LV filling pressures thereby promoting subendocardial perfusion, and hastens LV relaxation thereby prolonging the diastolic time interval for coronary perfusion. Chronic changes in coronary endothelial function could also influence diastolic LV performance. Enhanced coronary endothelial NO release, as occurs during chronic exercise or pacing, could explain increased LV diastolic distensibility observed in athlete's heart and in tachycardia cardiomyopathy. Reduced endothelial NO release, as occurs with aging or after transplantation, could contribute to reduced LV diastolic distensibility in the elderly or in allograft recipients.
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PMID:Paracrine coronary endothelial modulation of diastolic left ventricular function in man: implications for diastolic heart failure. 895 74

We studied the role of endothelium in control of forearm blood flow during reactive and exercise hyperemia in patients with heart failure as well as in normal subjects. First, endothelium-dependent forearm vasodilation in response to acetylcholine (ACh), substance P, and endothelium-independent forearm vasodilation in response to sodium nitroprusside (SNP) were examined in patients with heart failure and in normal subjects. Endothelium-dependent forearm vasodilation in response to ACh but not to substance P was impaired in patients with heart failure. Endothelium-independent forearm vasodilation to SNP was also preserved in patients with heart failure. Second, the role of nitric oxide (NO) in reactive hyperemia and exercise hyperemia was examined in normal subjects using NG-monomethyl-L-arginine (L-NMMA), a blocker of NO synthesis. Results suggest that NO plays a minimal role in peak reactive hyperemia and exercise hyperemia in normal human forearm vessels. Finally, we determined if L-arginine, a precursor of NO, improves impaired endothelium-dependent vasodilation due to ACh and reactive and exercise hyperemia in patients with heart failure. L-Arginine augmented impaired ACh-induced vasodilation as well as reactive and exercise hyperemia in patients with heart failure. Our results suggest that defective endothelial function may contribute to abnormal control of forearm blood flow in patients with heart failure.
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PMID:Role of endothelium in control of forearm blood flow in patients with heart failure. 895 81

Extracellular signaling molecules regulate intracellular events by way of complex transduction assemblies composed of several proteins: receptor, G protein, effector, inactivating enzyme. Much is known about the structure and function of these transducer proteins. A signaling molecule initiates transduction by binding to the receptor which then prompts the G protein to undergo a reaction cycle. This cycle involves guanine nucleotide binding and hydrolysis, G protein subunit dissociation, and interactions with an effector (e.g. adenylyl cyclase, phospholipase C), as well as with inactivating molecules. The result is altered generation of intracellular second messengers, protein transcription, or another profound cellular response. This signal transduction system also contains multiple mechanisms for turning off the signal such as phosphorylating, internalizing, or downregulating receptors, uncoupling the receptor-G protein complex, or cell-surface peptidases, and precipitating conformational changes in transducer elements. These aspects of signal transduction are examined in two well studied systems, namely the beta 2-adrenergic and the substance P transducers. Both complexes are important physiological neuroregulators in the gut and elsewhere. Pathophysiological mechanisms involving aberrent signal transduction have been implicated in various diseases including major common illnesses such as heart failure and gastrointestinal disorders such as cholera, other infectious diarrheas, and colitis.
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PMID:G protein-coupled receptor signaling: implications for the digestive system. 935 13

Available information from 1980 to 1997 on angiotensin converting enzyme (ACE) inhibitor-induced angioedema and its underlying mechanisms are summarised and discussed. The incidence of angioedema is low (0.1 to 0.2%) but can be considered as a potentially life-threatening adverse effect of ACE inhibitor therapy. This adverse effect of ACE inhibitors, irrespective of the chemical structure, can occur early in treatment as well as after prolonged exposure for up to several years. The estimate incidence is quite underestimated. The actual incidence can be far higher because of poorly recognised presentation of angioedema as a consequence of its late onset in combination with usually long term therapy. Also, a spontaneous reporting bias can contribute to an actual higher incidence of this phenomenon. The incidence can be even higher (up to 3-fold) in certain risk groups, for instance Black Americans. Treatment includes immediate withdrawal of the ACE inhibitor and acute symptomatic supportive therapy followed by immediate (and long term) alternative therapy with other classes of drugs to manage hypertension and/or heart failure. Preclinical and clinical studies for the elucidation of the underlying mechanism(s) of ACE inhibitor-associated angioedema have not generated definite conclusions. It is suggested that immunological processes and several mediator systems (bradykinin, histamine, substance P and prostaglandins) are involved in the pathogenesis of angioedema. A great part of all reviewed reports suggest a relationship between ACE inhibitor-induced angioedema and increased levels of (tissue) bradykinin. However, no conclusive evidence of the role of bradykinin in angioedema has been found and an exclusive role of bradykinin seems unlikely. So far, no clear-cut evidence for an immune-mediated pathogenesis has been found. In addition, ACE gene polymorphism and some enzyme deficiencies are proposed to be involved in ACE inhibitor-induced angioedema. Progress in pharmacogenetic and molecular biological research should throw more light on a possible genetic component in the pathogenesis of ACE inhibitor-associated angioedema.
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PMID:ACE inhibitor-induced angioedema. Incidence, prevention and management. 953 May 37

Activation of the renin-angiotensin-aldosterone system (RAAS) in left ventricular systolic dysfunction is a critically important determinant in the pathophysiologic processes that lead to progression of heart failure and sudden death. Angiotensin II, acting at the specific angiotensin receptor (AT1-R), activates a series of intracellular signaling sequences which are ultimately expressed within the cardiovascular system as vasoconstriction and associated vascular hypertrophy and remodeling. Angiotensin converting enzyme (ACE) inhibition leads to increases in the vasodilatory peptides bradykinin and substance P and at least an initial reduction in angiotensin II concentrations. AT1-R blocking drugs prevent access of angiotensin II to the AT1-R and thus prevent cellular activation. ACE inhibitors have clearly been demonstrated through a large number of clinical trials to increase survival in congestive heart failure, primarily by reducing the rate of progression of left ventricular dilatation and decompensation. However, this beneficial effect diminishes over time. Preliminary short-term clinical studies evaluating the efficacy of AT1-R blocking drugs in the treatment of heart failure have suggested that they elicit similar hemodynamic and neuroendocrine effects as do the ACE inhibitors. The combination ACE inhibitors and AT1-R blocking drugs offer the theoretical advantage of increasing bradykinin while blocking the actions of angiotensin II, and thus possibly show a synergistic effect. Again, preliminary studies have yielded encouraging results that are difficult to interpret because neither ACE inhibitor nor the AT1-R blocking drug doses were titrated to tolerance. Pharmacological manipulation of the RAAS has led to better understanding of its role in heart failure and improved clinical outcomes.
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PMID:Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of heart failure caused by left ventricular systolic dysfunction. 1036 49

Calcitonin gene-related peptide [CGRP]--a powerful vasodilator, is a 37 amino acid peptide that is find primarily in the central and peripheral nervous system. It affects the regulation of local blood flow, smooth muscle tone and glandular secretion. It is an endocrine regulator and in the lungs it also exerts a bronchoconstricting effect. CGRP has a proliferative effect on human endothelial cells. Therefore, it is important for the formation of new vessels, example, in ischemia, inflammations, and in the healing of wounds. Plasma levels of CGRP are increase in patients with chronic cardiac failure and sepsis, indicating that CGRP may be another important peptide in chronic illness. We have therefore measured the release of this peptide and another sensory peptide [Substance P (SP)]; a vasoconstrictor peptide [Endothelin (ET)]; and a perivascular peptide [Neuropeptide Y (NPY)], within 24 hours of injury, in the plasma of patients with soft tissue injury. Neuropeptides were measure by enzyme immunoassay technique. Median: (lower quartile-upper quartile) in pmol/L CGRP level was elevated in patients [50.37: (12.4-110.9)] compared to controls [13.9: (10.9-36.96)] p<0.05; Endothelin and NPY did not vary much between groups p=NS; ET: patients [8.7: (1.7-87.1), controls 8.8: (1.7-32.9)]; NPY: Patients [11.7: (10.5-14.99), controls 11: (10.3-12.8)]. SP was increase in patients [302.3: (79.9-707.3)], than controls [5.6: (3.2-36.6)] p<0.05. Furthermore, Elastase (a decisive marker for inflammation and infectious complications), was measure (ng/L), and found to be slightly higher in patients (102: 25.5-223), than controls (91.8: 45.9-127). In summary, plasma levels of sensory peptides increased significantly, in patients with soft tissue injury, in contrast to vasocostrictor peptides that remained unchanged. These sensory peptides may yet be another group of neuromodulators playing a significant role in immune, pain, inflammatory and wound healing in soft tissue injury patients.
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PMID:Calcitonin gene-related peptide and other neuropeptides in the plasma of patients with soft tissue injury. 1050 54

The cardiac mechano- and chemoreceptors are broadly distributed in the myocardium and coronary vessels. A portion of these receptors extends over the epicardium and pericardium and therefore can be excited by mechanical or chemical stimuli directly applied to the surface of the heart. Excitation of epicardial receptors by topical application of chemical compounds elicits a variety of reflex cardiovascular responses, without the vascular or systemic effects of the drug administered systemically. A considerable number of studies has used the epicardial sensory field as a tool to delineate the functional characteristics of the cardiac afferent neurones in normal as well as in pathological conditions. In this review we analyze the cardiovascular reflex responses induced by epicardial application of a variety of substances like bradykinin, nicotine, muscarine, isoprenaline, adenosine, potassium chloride, capsaicin, prostaglandins or substance P in physiological models and also in models with acute myocardial ischemia or heart failure. The data highlight the contribution of the epicardial sensory neurites to the overall control of the cardiovascular system and, on the other hand, strengthen the need for further investigations directed to better elucidate the reflex cardiovascular responses that may develop in patients with pericardial abnormalities.
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PMID:Cardiovascular reflex responses induced by epicardial chemoreceptor stimulation. 1072 29

Nitric oxide (NO) has effects on contractility, energetics and gene expression of failing myocardium. Initial studies on isolated cardiomyocytes showed NO to reduce systolic shortening but intracoronary infusions of NO-donors or of NO synthase (NOS) inhibitors failed to elicit changes in baseline LV contractility indices such as LVdP/dt(max). Intracoronary infusions of NO-donors or of substance P, which releases NO from the coronary endothelium, however demonstrated NO to induce a downward displacement of the left ventricular (LV) diastolic pressure-volume relation, consistent with increased LV diastolic distensibility. In end-stage failing myocardium, the increased oxygen consumption is related to reduced NO production and in isolated cardiomyocytes, NO blunts the norepinephrine-induced expression of the fetal gene programme thereby preserving myocardial calcium homeostasis.In dilated cardiomyopathy, changed endomyocardial NOS gene expression has been reported. Because of lower endomyocardial NOS gene expression in patients with higher functional class and lower LV stroke work, increased endomyocardial NOS gene expression seems to be beneficial rather than detrimental for the failing heart. A beneficial effect of increased NOS gene expression could result from NO's ability to increase LV diastolic distensibility, to augment LV preload reserve, to reduce myocardial oxygen consumption and to prevent downregulation of calcium ATPase. Upregulated endomyocardial NOS gene expression has also been reported in athlete's heart and could therefore play a role in physiological LV remodeling. Reduced endomyocardial NO content because of decreased NO or increased superoxide production could lower LV diastolic distensibility and contribute to diastolic heart failure. In many conditions such as aging, hypertension, diabetes or posttransplantation, the increased incidence of diastolic heart failure is indeed paralleled by reduced endothelium-dependent vasodilation.
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PMID:The role of nitric oxide in the failing heart. 1130 29

Coronary endothelial NO synthase expression and NO bioactivity were investigated at sequential stages during the progression of left ventricular hypertrophy. Male guinea pigs underwent abdominal aortic banding or sham operation. Left ventricular contractile function was quantified in isolated ejecting hearts. Coronary endothelial and vasodilator function were assessed in isolated isovolumic hearts in response to boluses of bradykinin (0.001 to 10 micromol/L), substance P (0.01 to 100 micromol/L), diethylamine NONOate (DEA-NO) (0.1 to 1000 micromol/L), N(G)-monomethyl-L-arginine monoacetate (L-NMMA) (10 mmol/L), and adenosine (10 mmol/L). At a stage of compensated left ventricular hypertrophy (3 weeks), left ventricular endothelial NO synthase protein expression was unaltered (Western blot and immunocytochemistry). Vasoconstriction in response to L-NMMA was increased in banded animals compared with sham-operated animals (13.8+/-2.1% versus 6.2+/-1.3%, n=10; P<0.05), but agonist- and DEA-NO-induced vasodilation was similar in the 2 groups. At a stage of decompensated left ventricular hypertrophy (8 to 10 weeks), left ventricular endothelial NO synthase protein expression was significantly lower in banded animals (on Western analysis: banded animals, 7.8+/-0.4 densitometric units; sham-operated animals, 12.2+/-1.7 densitometric units; n=5; P<0.05). At this time point, vasoconstriction in response to L-NMMA was similar in the 2 groups, but vasodilatation in response to bradykinin (30.9+/-2.4% versus 39.7+/-2.2%, n=10; P<0.05), DEA-NO (26.2+/-1.8% versus 34.6+/-1.8%, n=10; P<0.05), and adenosine (24.3+/-2.0% versus 35.7+/-2.0%, n=10; P<0.01) was attenuated in banded animals. These findings indicate that there is an increase in the basal activity of NO (without a significant change in endothelial NO synthase expression) in early compensated left ventricular hypertrophy, followed by a decrease in both endothelial NO synthase expression and NO bioactivity during the transition to myocardial failure.
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PMID:Divergent biological actions of coronary endothelial nitric oxide during progression of cardiac hypertrophy. 1150 88

Both angiotensin-converting enzyme (ACE) inhibitors and AT-1 receptor antagonists reduce the effects of angiotensin II, however they may have different clinical effects. This is because the ACE inhibitors, but not the AT-1 receptor antagonists, increase the levels of substance P, bradykinin and tissue plasminogen activator. The AT-1 receptor antagonists, but not the ACE inhibitors, are capable of inhibiting the effects of angiotensin II produced by enzymes other than ACE. On the basis of the present clinical trial evidence, AT-1 receptor antagonists, rather than the ACE inhibitors, should be used to treat hypertension associated with left ventricular (LV) hypertrophy. Both groups of drugs are useful when hypertension is not complicated by LV hypertrophy, and in diabetes. In the treatment of diabetes with or without hypertension, there is good clinical support for the use of either an ACE inhibitor or an AT-1 receptor antagonist. ACE inhibitors are recommended in the treatment of renal disease that is not associated with diabetes, after myocardial infarction when left ventricular dysfunction is present, and in heart failure. As the incidence of cough is much lower with the AT-1 receptor antagonists, these can be substituted for ACE inhibitors in patients with hypertension or heart failure who have persistent cough. Preliminary studies suggest that combining an AT-1 receptor antagonist with an ACE inhibitor may be more effective than an ACE inhibitor alone in the treatment of hypertension, diabetes with hypertension, renal disease without diabetes and heart failure. However, further trials are required before combination therapy can be recommended in these conditions.
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PMID:Angiotensin AT-1 receptor antagonism: complementary or alternative to ACE inhibition in cardiovascular and renal disease? 1243 89

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