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)

Adrenomedullin (AM), identified from pheochromocytoma and having 52 amino acids, elicits a long-lasting vasodilatation and diuresis. AM is mainly mediated by the intracellular adenylate cyclase coupled with cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) -cyclic guanosine monophosphate (cGMP) pathway through its specific receptor. The calcitonin receptor-like receptor (CLCR) and receptor-activity modifying protein (RAMP) 2 or RAMP3 models have been proposed as the candidate receptor. AM is produced mainly in cardiovascular tissues in response to stimuli such as shear stress and stretch, hormonal factors and cytokines. Recently established AM knockout mice lines revealed that AM is essential for development of vitelline vessels of embryo. Plasma AM levels elevate in cardiovascular diseases such as heart failure, hypertension and septic shock, where AM may play protective roles through its characteristic biological activities. Human AM gene delivery improves hypertension, renal function, cardiac hypertrophy and nephrosclerosis in the hypertensive rats. AM decreases cardiac preload and afterload and improves cardiac contractility and diuresis in patients with heart failure and hypertension. Advances in gene engineering and receptor studies may contribute to further understandings of biological implication and therapeutic availability of AM.
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PMID:A review of the biological properties and clinical implications of adrenomedullin and proadrenomedullin N-terminal 20 peptide (PAMP), hypotensive and vasodilating peptides. 1175 55

Adrenomedullin and the natriuretic peptides exert vasodilator, natriuretic, and aldosterone-inhibitory actions, making augmentation of both systems potential therapeutic strategies in heart failure. Adrenomedullin and an endopeptidase inhibitor (SCH32615) were administered separately and in combination in 8 sheep with heart failure. Compared with the control condition, SCH32615 (5 mg bolus+1 mg/kg per hour infusion for 3 hours) reduced arterial pressure, left atrial pressure, and peripheral resistance and increased cardiac output, urinary volume, sodium, creatinine, and cAMP excretion. Plasma atrial and brain natriuretic peptide and cGMP concentrations were increased, whereas aldosterone tended to fall. Adrenomedullin (50 ng/kg per minute infusion for 3 hours) induced directionally similar but significantly greater changes in all hemodynamic variables compared with SCH32615. Urinary cAMP, sodium, and creatinine excretion rose, whereas urinary volume was maintained. Circulating adrenomedullin, cAMP, renin, and angiotensin II levels were increased, aldosterone was reduced, and natriuretic peptide levels were unchanged. Coadministration of adrenomedullin and SCH32615 produced hemodynamic effects greater than those achieved during adrenomedullin administration alone. Despite the larger falls in blood pressure, renal function (urinary volume, sodium excretion, and creatinine clearance) was improved to a level similar to that during SCH32615 administration. Elevations in plasma adrenomedullin and cAMP were greater than those during adrenomedullin administration alone, whereas increments in natriuretic peptides were similar to those during SCH32615 alone. Plasma renin and angiotensin II were increased and aldosterone levels were reduced. In conclusion, cotreatment with adrenomedullin and an endopeptidase inhibitor has beneficial hemodynamic and renal effects in heart failure beyond those of either agent separately.
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PMID:Combined endopeptidase inhibition and adrenomedullin in sheep with experimental heart failure. 1179 85

Advances in the treatment of heart failure may require manipulation of neurohumoral responses to cardiac impairment in addition to the established strategy of angiotensin-converting enzyme (ACE) inhibition. Importantly, since new treatments are likely to be used in conjunction with ACE inhibition therapy, the effects of the combination of agents need to be assessed. Adrenomedullin (ADM) is a peptide with potent vasodilator and natriuretic actions. ADM and an ACE inhibitor (captopril) were administered for 3 h both separately and together in eight sheep with heart failure. Both ADM and captopril alone reduced arterial pressure, left atrial pressure (greater with captopril) and peripheral resistance, and increased cardiac output (greater with ADM). Compared with either treatment separately, combined ADM+captopril produced directionally similar but significantly greater changes in all haemodynamic variables (particularly falls in blood pressure). ADM increased renal sodium and creatinine excretion and creatinine clearance, and maintained urine output. Captopril and ADM+captopril reduced creatinine excretion and creatinine clearance, while urine volume and sodium excretion were not significantly altered. Plasma renin activity rose with all active treatments, whereas angiotensin II levels rose during ADM, but fell during captopril and ADM+captopril. Aldosterone was reduced by all active treatments. ADM+captopril reduced plasma noradrenaline (norepinephrine). In conclusion, short-term co-treatment with ADM and an ACE inhibitor produced significantly greater decreases in ventricular filling pressures and cardiac afterload, and increases in cardiac output, compared with either treatment alone. Despite the greater falls in blood pressure (and presumably renal perfusion pressure), renal function was maintained at a level similar to that observed with captopril alone.
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PMID:Combined angiotensin-converting enzyme inhibition and adrenomedullin in an ovine model of heart failure. 1204 20

Adrenomedullin (ADM) release is enhanced in pheochromocytoma, chronic heart failure (HF), hypertension and renal diseases. This study was designed to test the hypothesis that ADM secretion increases also in response to acute stimuli, such as static effort and to compare plasma ADM response to this stimulus in patients with chronic HF and healthy persons. Eight male HF patients (II/III class NYHA) and eight healthy subjects (C) performed two 3-min bouts of static handgrip at 30% of maximal voluntary contraction, alternately with each hand without any break between the bouts. At the end of both exercise bouts and in 5 min of the recovery period, plasma ADM and catecholamines were determined. In addition, heart rate, blood pressure, and stroke volume (SV) were measured. The baseline plasma ADM and noradrenaline levels were higher, whilst plasma adrenaline and SV were lower in HF patients than in C group. The 1st exercise bout caused an increase in plasma ADM from 3.32 +/- 0.57 to 4.98 +/- 0.59 pmol l(-1) (p<0.01) in C and from 6.88 +/- 0.58 to 7.80 +/- 0.43 pmol x l(-1) (p<0.02) in HF patients. The 2nd exercise bout did not produce further elevation in plasma ADM and during recovery the hormone concentration declined to pre-exercise or lower values. There were no differences between groups in exercise-induced increases in plasma ADM. Plasma ADM correlated with SV (r = -0.419) and with noradrenaline concentrations (r = 0.427). It is concluded that static exercise causes the short-lasting increase in plasma ADM concentration which is similar in healthy subjects and in patients with mild heart failure.
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PMID:Effect of static handgrip on plasma adrenomedullin concentration in patients with heart failure and in healthy subjects. 1212 Aug 96

Short-term administration of adrenomedullin, a recently discovered peptide with potent vasodilator, natriuretic, and aldosterone-inhibitory actions, has beneficial effects in experimental and clinical heart failure. The effects of prolonged adrenomedullin administration have not previously been assessed in this setting. Consequently, in 16 sheep with pacing-induced heart failure, we infused either adrenomedullin (10 ng/kg per minute; n=8) or a vehicle control (Hemaccel; n=8) for 4 days. Compared with control data, infusion of adrenomedullin persistently increased circulating levels of the peptide (by approximately 9.5 pmol/L; P<0.001), in association with prompt (15 minutes) and sustained (4 days) increases in cardiac output (day 4, 27%), and reductions in peripheral resistance (30%), mean arterial pressure (13%), and left atrial pressure (24%; all, P<0.001). Adrenomedullin also significantly enhanced urinary sodium excretion (day 4, 3-fold; P<0.05), creatinine excretion (1.2-fold; P<0.001), and creatinine clearance (1.4-fold; P<0.001) over the 4 days of treatment, whereas urine volume and cAMP excretion tended to be elevated (both, 0.1>P>0.05). Plasma renin activity was increased (P<0.05), whereas aldosterone levels were reduced in a sustained fashion (P<0.01). Plasma endothelin rose transiently (hours 1 to 6) after initiation of treatment (P<0.05). Despite substantial cardiac unloading, plasma concentrations of the natriuretic peptides were not significantly different from control. In conclusion, long-term administration of adrenomedullin induces pronounced and sustained cardiovascular and renal effects in experimental heart failure, including reductions in cardiac preload and afterload, as well as augmentation of cardiac output, sodium excretion, and glomerular filtration. These findings support the concept of adrenomedullin as a protective hormone during hemodynamic compromise with therapeutic potential in heart failure.
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PMID:Long-term adrenomedullin administration in experimental heart failure. 1241 60

Adrenomedullin (AM) and atrial and brain natriuretic peptides (ANP and BNP) exert vasodilator and natriuretic actions and are thought to share roles in counteracting the progression of hypertension or heart failure as circulating or locally-acting hormones. However, little data is available with regard to their roles in subjects who have no apparent cardiovascular diseases. The present study was carried out to identify the factors that affect plasma levels of AM, ANP and BNP in the general population. We measured the plasma levels of AM, ANP and BNP in 184 local residents who had a scheduled regular health checkup, and compared the findings with those for other clinical parameters. Univariate analyses showed that the plasma levels of AM, ANP and BNP were significantly correlated with age. The plasma levels of ANP and BNP were also significantly correlated with systolic blood pressure (SBP) and with pulse pressure (PP), an indicator of the stiffness of the great vessels. Multivariate analyses conducted using a stepwise method revealed that age was a significant, independent variable for the plasma levels of AM, ANP and BNP. In addition, PP was a significant factor for the plasma levels of ANP and BNP, while the plasma AM was significantly associated with body mass index (BMI). Thus, the plasma levels of AM, ANP and BNP all increased in association with aging, and those of ANP and BNP increased in association with PP, suggesting possible relationships between the plasma levels and age-related changes in the cardiovascular system.
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PMID:Plasma levels of adrenomedullin and atrial and brain natriuretic peptides in the general population: their relations to age and pulse pressure. 1248 13

Adrenomedullin (ADM) is a 52-amino acid peptide with structural homology to calcitonin gene-related peptide (CGRP) initially isolated from human pheochromocytoma. ADM is synthesized by many mammalian tissues including the adrenal medulla, endothelial and vascular smooth muscle cells, myocardium and central nervous system. ADM binds to plasma membrane receptors composed of calcitonin receptor-like receptor (CRLR), a member of serpentine receptor superfamily, and receptor activity modifying protein (RAMP) type 2 or 3. ADM has also some affinity for CGR(1) receptor composed of CRLR and RAMP1. ADM dilates blood vessels in both endothelium-dependent and independent manner and decreases systemic arterial pressure. Intrarenally administered ADM increases natriuresis by vascular and tubular mechanisms. In addition, ADM inhibits migration and proliferation of vascular smooth muscle cells and attenuates myocardial remodelling by inhibiting protein synthesis in cardiomyocytes and proliferation of cardiac fibroblasts. ADM is expressed in various tissues from early stage of embryogenesis and is also synthesized in placenta, uterus and fetal membranes. Plasma ADM level is increased in arterial hypertension, acute coronary syndromes, heart failure, renal diseases and septic shock, being involved in the pathophysiology of these disorders. Experimental ADM treatment is beneficial in arterial and pulmonary hypertension, heart failure, septic shock and ischemia/reperfusion injury. Proadrenomedullin N-terminal peptide (PAMP) is another product of ADM gene which is co-secreted by ADM-producing tissues, with some effects similar and some opposite to ADM.
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PMID:Adrenomedullin--what do we know 10 years since its discovery? 1504 74

Adrenomedullin (AM), inducing a potent and powerful hypotensive activity caused by dilatation of resistance vessels, has elicited interest for its cardiovascular actions. AM is secreted from various cell type, including vascular endothelial and smooth muscle cell. AM plasma levels are increased in various cardiovascular diseases as heart failure and hypertension and may be involved in pathophysiological changes in cardiovascular diseases.
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PMID:[Adrenomedullin in cardiovascular pathology]. 1514 54

Adrenomedullin, a 52-amino acid residue peptide, has numerous biological actions which are of potential importance to cardiovascular homeostasis, growth and development of cardiovascular tissues and bone, prevention of infection, and regulation of body fluid and electrolyte balance. Studies in man using intravenous infusion of the peptide have demonstrated that, at plasma levels detected after myocardial infarction or in heart failure, adrenomedullin reduces arterial pressure, increases heart rate and cardiac output, and activates the sympathetic and renin-angiotensin systems but suppresses aldosterone. The thresholds for these responses differ, being lower under some experimental circumstances for arterial pressure than for the other biological effects. Adrenomedullin administration inhibits the pressor and aldosterone-stimulating action of angiotensin II in man. By contrast, the pressor effect of norepinephrine is little altered by concomitant adrenomedullin administration. Although in the absence of a safe, specific antagonist of the actions of endogenous adrenomedullin it is difficult to be certain about the physiological and pathophysiological importance of this peptide in man, current evidence suggests that it serves to protect against cardiovascular overload and injury. Hope has been expressed that adrenomedullin or an agonist specific for adrenomedullin receptors might find a place in the treatment of cardiovascular disorders.
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PMID:Hemodynamic and hormonal actions of adrenomedullin. 1527 27

Adrenomedullin (AM) is a potent, long-lasting vasoactive peptide originally isolated from human pheochromocytoma. Since its discovery, serum and tissue AM expression have been shown to be increased in experimental models and in patients with cardiac hypertrophy, myocardial infarction and end-stage heart failure with several beneficial effects. Considerable evidence exists for a wide range of autocrine, paracrine and endocrine mechanisms for AM which include vasodilatory, anti-apoptotic, angiogenic, anti-fibrotic, natriuretic, diuretic and positive inotropic. Thus, through regulation of body fluid or direct cardiac mechanisms, AM has additive and beneficial effects in the context of heart disease. Notable molecular mechanisms of AM include cyclic adenosine monophosphate, guanosine-3',5'-monophosphate, PI3K/Akt and MAPK-ERK-mediated cascades. Given the endogenous and multifunctional nature of AM, we consider this molecule to have great potential in the treatment of cardiovascular diseases. In agreement, early experimental and preliminary clinical studies suggest that AM is a new and promising therapy for cardiovascular diseases.
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PMID:Adrenomedullin: molecular mechanisms and its role in cardiac disease. 1658 14


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