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

ALTERATIONS OF THE ENDOTHELIUM: Because of its anatomic position between circulating blood and smooth muscle cells, the vascular endothelium is a prime target for cardiovascular diseases such as hypertension, hypercholesterolemia, diabetes or ischemia. The morphological changes occurring in the endothelium have been known for many years, but it was only recently that the functional alterations have been described. IMPACT OF NO: Under physiological conditions, the vascular endothelium plays a protective role by secreting relaxation factors. In the disease state, the synthesis and release of NO may be reduced or even abolished. The exact significance of endothelium-dependent vasodilatation disorders remains a topic of research, but the properties of NO strongly suggest it is involved in several diseases. For some diseases it is still a question as to whether the observed anomalies are the cause or the consequence of the underlying disease. DISEASE-SPECIFIC CHANGES: NO is known to be reduced in atherosclerosis, either because of less synthesis or accelerated degradation. In different experimental modules of hypertension, the baseline level of NO release appears to be decreased. Conversely, NO release can be normal, reduced or increased in diabetes. In heart failure, there appears to be not only a permanent alteration in NO secretion, but also an increase in factors stimulating vascular contraction, contributing to an altered capacity for vascular adaptation in these patients.
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PMID:[Nitric oxide (NO), vascular protection factor. NO related cardiovascular diseases]. 976 31

Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed ("stunning"), or persistent if perfusion remains reduced ("hibernation") and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance.
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PMID:[Transition of myocardial ischemia to heart failure]. 981 48

The vascular endothelium plays a key role in the local regulation of vascular tone by the release of vasodilator substances (i.e. endothelium-derived relaxing factor (EDRF = nitric oxide, NO) and prostacyclin) and vasoconstrictor substances (i.e. thromboxane A2, free radicals, or endothelin). Using either agents like acetylcholine or changes in flow to stimulate the release of EDRF (NO), clinical studies have revealed the importance of EDRF in both basal and stimulated control of vascular tone in large epicardial coronary arteries and in the coronary microcirculation. The regulatory function of the endothelium is altered by cardiovascular risk factors or disorders such as hypercholesterolemia, chronic smoking, hypertension or chronic heart failure. Endothelial dysfunction appears to have detrimental functional consequences as well as adverse longterm effects, including vascular remodelling. Endothelial dysfunction is associated with impaired tissue perfusion particularly during stress and paradoxical vasoconstriction of large conduit vessels including the coronary arteries. These effects may cause or contribute to myocardial ischemia. Several mechanisms may be involved in the development of endothelial dysfunction, such as reduced synthesis and release of EDRF or enhanced inactivation of EDRF after its release from endothelial cells by radicals or oxidized low-density lipoprotein (LDL). Increased plasma levels of oxidized LDL have been noted in chronic smokers and are related to the extent endothelial dysfunction, raising the possibility that chronic smoking potentiates endothelial dysfunction by increasing circulating and tissue levels of oxidized LDL. In heart failure, cytokines and/or reduced flow (reflecting reduced shear stress) may be involved in the development of endothelial dysfunction and can be reversed by physical training. Other mechanisms include an activated renin-angiotensin system (i.e. postmyocardial infarction) with increased breakdown of bradykinin by enhanced angiotensin converting enzyme (ACE) activity. There is evidence that endogenous bradykinin is involved in coronary vasomotor control both in coronary conduit and resistance vessels. ACE inhibitors enhance endothelial function by a bradykinin-dependent mechanism and probably also by blunting the generation of superoxide anion. Endothelial dysfunction appears to be reversible by administering L-arginine, the precursor of nitric oxide, lowering cholesterol levels, physical training, antioxidants such as vitamin C, or ACE inhibition.
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PMID:Endothelial dysfunction in human disease. 1007 15

Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. For vascular endothelium, hepatocyte growth factor (HGF) is one of the most potent and specific growth factors, which acts protectively against endothelial dysfunction. HGF production is downregulated by angiotensin II (Ang II) in vitro. We hypothesized that HGF production is impaired as the result of increased Ang II in patients with congestive heart failure, and that if so, the impaired production should be restored with angiotensin-converting enzyme inhibitors (ACE-I). We studied 16 patients with congestive heart failure caused by previous anterior myocardial infarction in whom left ventricular ejection fraction was 35+/-8% (mean+/-SD). Before and approximately 4 weeks after the treatment with ACE-I, blood samples were collected to measure the levels of HGF, Ang II, and brain natriuretic peptide as a biochemical marker for severity of heart failure. We also studied 5 control subjects, in whom heparin increased HGF production to 48+/-5-fold. However, in patients with heart failure, HGF response to heparin was significantly attenuated (24+/-5-fold, P<0.05 vs control). Therapy with ACE-I decreased the levels of Ang II and brain natriuretic peptide and restored HGF production in response to heparin by 43+/-7-fold, comparable to the control response. In conclusion, impaired HGF production was restored after the treatment with ACE-I probably by the mechanism of Ang II suppression. This novel effect of ACE-I may contribute to the clinical improvement in patients with heart failure and thereby may have an important therapeutic implication.
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PMID:Angiotensin-converting enzyme inhibition restores hepatocyte growth factor production in patients with congestive heart failure. 1037 19

The syndrome of heart failure causes besides a deterioration in the contractile function of the heart significant alterations of peripheral circulation and skeletal muscles. The distribution of the regional blood flow is influenced by systemic and local neurohumoral factors. The local factors are released by the vascular endothelium or are of nonendothelial origin. The diminution of cardiac output leads to neurohumoral alterations which eventually influence the blood flow distribution: in vital organs, such as the heart and the brain, it is preserved; in the splanchnic, kidney, muscle and skin territories it is diminished. Muscles changes (muscle atrophy, reduction of type I fibres and a relative increase of type IIb fibres) are the main cause restricting the exercise. Techniques of physical rehabilitation associated with proper medication may lead to the improvement of these alterations.
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PMID:[Peripheral vascular remodelling and changes to the skeletal muscles in heart failure]. 1075 41

Endothelin (ET) -1 is a potent vasoconstrictor and promitogenic peptide produced by the vascular endothelium. The ET system is activated in atherosclerosis and in most cardiovascular conditions associated with increased vascular tone and remodelling. There are two ET-receptor (ET-R) subtypes: the ETA-Rs mediate smooth muscle vasoconstriction and proliferation, and the more complex ETB-Rs have antagonistic actions - they serve a dual role of clearance and vasodilation in the endothelium, while in smooth muscle cells they also provoke vasoconstriction. Selective ETA-R and nonselective ETA/B-R antagonists are entering the clinical development phase. These agents have shown their effectiveness in the therapy of various models of heart failure, pulmonary hypertension, systemic hypertension and ischemia-reperfusion and in the prevention of restenosis. In patients with congestive heart failure, short term ET-antagonist (ET-R) therapy provides hemodynamic and symptomatic improvement. Because of the dual role of the ETB-R, nonselective antagonists may provide greater or fewer benefits than selective ETA-R antagonists: a lack of direct comparison of the two categories of agents, however, does not allow this distinction at present. In the evaluation of this new class of therapeutic agents, particular attention should be paid to potency and receptor selectivity of a compound, the alterations in ETA-R and ETB-R activity brought on by pathological conditions, the proportions of ETA versus ETB-R of the target system, and finally, the net importance of the possible protective role of the endothelial ETB versus the deleterious effects of the smooth muscle ETB-R.
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PMID:Endothelin receptor antagonists and their developing role in cardiovascular therapeutics. 1093 9

Campylobacter fetus subspecies fetus has a predilection for vascular endothelium. This report describes a case of a prosthetic valve infective endocarditis due to this microorganism. Despite adequate antibiotic combination treatment, valvular vegetations and perivalvular suppurative complications evolved, leading to valvular dysfunction, heart failure and death. Only three other cases of C. fetus prosthetic valve endocarditis have been described previously. Campylobacter fetus bacteraemia must be considered cautiously, because of the risk of late cardiac or vascular complications.
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PMID:Fatal prosthetic valve endocarditis due to Campylobacter fetus. 1102 67

Adrenomedullin (ADM) is a vasodilator produced by vascular endothelium and smooth muscle cells. Although plasma ADM levels are increased in patients with hypertension, heart failure, and myocardial infarction, little information exists regarding the microvascular response to ADM in the human heart. In the present study we tested the hypothesis that ADM produces coronary arteriolar dilation in humans and examined the mechanism of this dilation. Human coronary arterioles were dissected and cannulated with micropipettes. Internal diameter was measured by video microscopy. In vessels constricted with ACh, the diameter response to cumulative doses of ADM (10(-12)-10(-7) M) was measured in the presence and absence of human ADM-(22-52), calcitonin gene-related peptide-(8-37), N(omega)-nitro-L-arginine methyl ester (L-NAME), indomethacin (Indo), (1)H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, SQ-22536, or KCl (60 mM). ADM dilated human coronary arterioles through specific ADM receptors (maximum dilation = 69 +/- 11%). L-NAME or N-monomethyl-L-arginine attenuated dilation to ADM (for L-NAME, maximum dilation = 66 +/- 7 vs. 41 +/- 13%, P < 0.05). Thus the mechanism of ADM-induced dilation involves generation of nitric oxide. However, neither (1)H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one, SQ-22536, nor Indo alone altered dilation to ADM. High concentrations of KCl blocked dilation to ADM. The magnitude of ADM dilation was reduced in subjects with hypertension. We propose that, in human coronary arterioles, ADM elicits vasodilation in part through production of nitric oxide and in part through activation of K(+) channels, with little contribution from adenylyl cyclase. The former dilator mechanism is independent of the more traditional pathway involving activation of soluble guanylate cyclase.
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PMID:Human coronary arteriolar dilation to adrenomedullin: role of nitric oxide and K(+) channels. 1108 13

Recent evidence suggests the possibility that enhanced inactivation of endothelium-derived nitric oxide (NO) by oxygen free radical (OFR) may cause endothelial dysfunction in heart failure (HF). To test this hypothesis, we examined the effect of antioxidant therapy on endothelium-dependent vasodilation of the coronary circulation in a canine model of tachycardia-induced HF. Endothelium-dependent vasodilation was less than that in controls, and OFR formation in coronary arterial and myocardial tissues was greater in HF dogs than those in controls. The immunohistochemical staining of 4-hydroxy-2-nonenal, OFR-induced lipid peroxides was detected in coronary microvessels of HF dogs. Intracoronary infusion of the cell-permeable OFR scavenger Tiron inhibited OFR formation and improved endothelium-dependent vasodilation in HF dogs but not in controls. The NO synthesis inhibitor N(G)-monomethyl-L-arginine (L-NMMA) diminished the beneficial effect of Tiron in HF dogs. Endothelium-independent vasodilation was similar between control and HF dogs, and no change in its response was noted by Tiron or Tiron plus L-NMMA in either group. In summary, antioxidant treatment with Tiron improved coronary vascular endothelium-dependent vasodilation by increasing NO activity in tachycardia-induced HF. Thus coronary endothelial dysfunction in HF may be, at least in part, due to increased inactivation of NO by OFR.
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PMID:Increased inactivation of nitric oxide is involved in coronary endothelial dysfunction in heart failure. 1112 19

The benefit effects of nitric oxide (NO) donors in acute heart failure have led to the development of vasodilators as treatment of chronic heart failure. However, the mechanisms involved in the effects of NO are complex and still discussed. In chronic heart failure, the eNOS downregulation in vascular endothelium explains the alteration of endothelial function. In addition, in the myocardium, cytokines induce the expression of inducible nitric oxide synthase (iNOS) which increase NO production by myocytes and surrounding cells. This excess of NO production, associated with anion superoxide synthesis, limits the inotropic properties of catecholamines and exert proapoptotic effects. The role of NO donors in heart failure treatment is still controversial but by reducing preload they improve patient's symptoms. Beside blockade of the renin-angiotensin system, the angiotensin converting enzyme inhibitors act via the inhibition of bradykinin degradation which increase NO levels. Finally, vascular endothelial NO expression is improved by exercise training and participates in the improvement of exercise capacity in patients with chronic heart failure involved in cardiac readaptation program.
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PMID:[Role of nitric oxide in heart failure]. 1132 16


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