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

Heart function and plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA) and angiotension II (Ang II) were examined with echocardiography and radioimmunoassay in 9 patients with dilated cardiomyopathy (DCM), 41 with rheumatic heart disease (RHD), 29 with hyperthyroidism (Ht) and 24 normal subjects. ANP level was significantly increased as heart failure progressed (P < 0.01 and 0.001). There was negative correlation between ANP and left ventricular fractional shortening, and between ANP and ejection fraction in DCM and Ht groups. There was positive correlation between ANP and maximal left atrial diameter, right atrial area, and diastolic diameter or volume of left ventricle in DCM and RHD groups, and negative correlation between ANP and peak flow velocity in aorta or through mitral valve in DCM group (r = -0.608, P < 0.05 and r = 0.710, P < 0.05). These findings suggest that the stronger the myocardial contractility and the faster the blood flow, the lower the plasma ANP level.
 ...
PMID:[Influence of cardiac structure, blood flow velocity and heart function on circulating atrial natriuretic peptide and renin-angiotension system]. 780 22

Left ventricular hypertrophy (LVH) is a common consequence of hypertension, and an independent risk factor for cardiovascular morbidity and mortality. The presence and severity of LVH is best determined by echocardiography and expressed as left ventricular mass index or left ventricular wall thickness. Pathological LVH, in response to pressure or volume load on the heart, is characterised by myocyte hypertrophy and hypertrophy/hyperplasia of nonmyocyte cells within the myocardium. Angiotensin II and aldosterone are promoters of increased fibroblast activity and a significant increase in collagen fibres in the myocardium. Early diagnosis and treatment of hypertension has significantly decreased the incidence of LVH and subsequent heart failure in many countries, but the choice of antihypertensive therapy alters the rate of reversal of LVH and the subsequent development of heart failure. Angiotensin converting enzyme (ACE) inhibitors, beta-blockers and calcium channel blockers produce the most rapid reversal of hypertrophy. Meta-analysis of these many small trials suggests an advantage of ACE inhibitors over other groups of antihypertensive agents.
 ...
PMID:Hypertrophy to failure. 780 8

Neutral endopeptidase inhibition (NEP-I) and angiotensin converting enzyme inhibition (ACE-I) act synergistically to produce acute beneficial hemodynamic effects in models of heart failure. Blockade of the formation of angiotensin II (Ang II) acting together with potentiation of the natriuretic peptides, bradykinin and other vasoactive peptides may mediate the interaction of dual enzyme inhibition. In this study, the potential roles of Ang II repression and bradykinin potentiation were evaluated in conscious cardiomyopathic hamsters with compensated heart failure. The Ang II AT1 receptor antagonist, SR 47436 (BMS-186295), was administered at 30 mumol/kg, i.v. followed by i.v. infusion at 1 mumol/kg/min in combination with NEP-I (SQ-28603 at 30 mumol/kg i.v.). Cardiac preload (left ventricular end diastolic pressure) and afterload (left ventricular systolic pressure) decreased significantly more after the combination of Ang II blockade and NEP-I than after either treatment alone. This indicated that repression of Ang II contributes importantly to the NEP-I/ACE-I interaction. Bradykinin B2 receptor antagonism by Hoe 140 at 100 micrograms/kg, i.v. significantly blunted the decrease in left ventricular end diastolic pressure but not the decrease in left ventricular systolic pressure after dual NEP-I/ACE-I (SQ-28603 and enalaprilat each at 30 mumol/kg, i.v.). This suggests that bradykinin potentiation contributes to the preload-reducing, but not the afterload-reducing, acute effects of NEP-I/ACE-I. Hence, both Ang II repression and bradykinin potentiation are factors contributing to the synergistic hemodynamic effects of combined NEP-I and ACE-I in hamsters with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Repression of angiotensin II and potentiation of bradykinin contribute to the synergistic effects of dual metalloprotease inhibition in heart failure. 785 75

Myocardial hypertrophy is an established risk factor for cardiovascular morbidity and mortality. Beyond quantitative and mechanical aspects hypertrophy is associated with alterations in cardiac gene expression, resulting in a more fetal-like myocyte phenotype with a fragile Ca++ homeostasis. Depressed expression of sarcoplasmatic reticulum ATPase is the hallmark of this overload phenotype. Conversely, the gene expression and the activity of sodium calcium exchanger is up-regulated in endstage heart failure. Both alterations contribute to prolonged cytosolic Ca++ transients, disturbed relaxation and, probably, to electrophysiologic instability. Angiotensin II is a growth promoting agent and several lines of circumferential evidence suggest that the local formation of angiotensin II might contribute to the trophic response and phenotype shift in cardiac overload. The cardiac gene expression of angiotensin converting enzyme and angiotensinogen is increased early after cardiac overload and in patients with severe heart failure. Chronic ACE inhibition suppresses plasma and tissue ACE activity, reduces LV hypertrophy and improves long-term survival. The hallmark of the peripheral adaptation in chronic heart failure is systemic vasoconstriction, associated with neurohumoral activation. Several mechanisms are involved in the impaired peripheral perfusion, including increased sympathetic tone and increased vascular stiffness. Recently, data suggest an important role of the endothelium for perfusion of skeletal muscle in heart failure. Endothelium-dependent dilation of resistance vessels is blunted in patients with severe chronic heart failure. Conceivably, this abnormality may be involved in the impaired reactive hyperemia in patients with chronic heart failure. Moreover, alterations of skeletal muscle emerge in chronic heart failure contributing to reduced exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Heart failure: an update on pathophysiology. 786 17

Recent developments in the techniques of molecular biology and the availability of inhibitors of the renin-angiotensin system have provided new insight into renin-angiotensin research. The control mechanism of renin release and the metabolism of circulating renin have been well characterized on the molecular level. Angiotensin II has been shown to play an important role not only in the regulation of blood pressure but also in cell growth and hypertrophy. ACE inhibitors are effective for the treatments of hypertension and heart failure. Furthermore, recent studies suggest that ACE inhibitors may prevent atherosclerosis and glomerulosclerosis. Angiotensin II receptor antagonists have similar beneficial effects. These effects of ACE inhibitors and angiotensin II-receptor antagonists may be mediated by growth factors and the extracellular matrix.
 ...
PMID:[Pharmacology of the renin-angiotensin system]. 795 18

Coronary resistance arteriolar diameter importantly regulates myocardial blood flow, and is influenced by circulating neurohumoral agents. Angiotensin II (A-II) is a circulating polypeptide that is chronically elevated in heart failure and serves as a potent peripheral vasoconstrictor agent. However, its effects on isolated coronary resistance arterioles is relatively unknown. We compared the vasomotor effects of A-II on coronary epicardial and resistance arterioles in vitro from both the canine and porcine heart in order to determine the effects of A-II in different vascular beds and species. Epicardial rings were studied under isometric recording conditions, while resistance arterioles (50-150 microns) were studied in vitro using a video imaging system to record diameter. A-II, whether applied to passively distended or preconstricted porcine resistance arterioles, did not cause vasoconstriction when applied as a bolus or as cumulative doses. In preconstricted canine resistance arterioles, A-II elicited dose-dependent vasodilation (EC50 = 0.2 nM). In passively distended canine arterioles, high concentrations of A-II (0.1 microM) applied as a bolus elicited transient vasoconstriction in 28% of the vessels studied. In large epicardial rings, A-II was a weak vasoconstrictor, with greater potency in canine arteries compared to porcine arteries. In canine arteries, vasoconstriction to A-II was augmented after incubation with indomethacin. In contrast to the findings in canine arteries, the A-II vasoconstrictor response in porcine coronary arteries was decreased after incubation with indomethacin or removal of the endothelium. Thus, A-II elicits the release of a vasodilator prostanoid in epicardial canine coronary arteries and a vasoconstrictor prostanoid in porcine vessels which modulate the vasomotor action of A-II.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of angiotensin II on canine and porcine coronary epicardial and resistance arteries. 798 58

The renin-angiotensin and cardiac natriuretic systems play an important role in the pathophysiology of congestive heart failure (CHF). The status of the membrane-bound pulmonary and renal activities of three ectoenzymes involved in the regulation of these systems-angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP), and aminopeptidase A (APA)-was investigated in Wistar rats 3 months after induction of myocardial infarction (MI) and in sham-operated (control) rats. Plasma renin activity and ACE activity, plasma angiotensin II (Ang II) levels, and atrial natriuretic factor levels were simultaneously determined. The lung ACE activity was decreased in MI rats compared with control rats (P < .0001), and this decrease depended on the severity of the heart failure. In contrast, plasma ACE activity was increased in MI rats (P < .01), and this increase was also proportional to the severity of MI. Northern blot analysis showed that the lung ACE mRNA level in severe MI rats was half that of the control rats. Renal ACE activity of the MI rats was not affected, and neither renal or pulmonary NEP nor pulmonary APA activities were altered. Thus, lung ACE gene expression appears to be both organ- and enzyme-specifically regulated during CHF. Whereas plasma renin was increased in heart failure rats, plasma Ang II levels were not different from those of control rats. Thus, decreased lung ACE activity could possibly contribute to keeping plasma Ang II levels in the normal range. The decrease in lung ACE activity and mRNA levels, combined with increased plasma ACE activity, represents a novel aspect of endothelial dysfunction in CHF.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Discrepancy between plasma and lung angiotensin-converting enzyme activity in experimental congestive heart failure. A novel aspect of endothelium dysfunction. 806 19

Congestive heart failure is often preceded by a latent or preclinical phase in which patients are relatively asymptomatic. During this period, there is neuroendocrine activation, left ventricular dysfunction, and remodeling of the heart. The extent to which these activities are interrelated is unclear, but it appears from experimental studies that myocardial damage is associated with chronic sympathetic nervous system activation, left ventricular hypertrophy, and a subsequent increase in left ventricular volume. The nondamaged myocardial tissue demonstrates enhanced messenger RNA for angiotensinogen and angiotensin converting enzyme activity. Angiotensin II along with other trophic signals may prime the cell for "growth." Alteration of left ventricular function may produce unusual loading conditions on the myocardium. Stretch of membrane-bound ion channels may impart mechanical signals that may be transduced and expressed as cellular hypertrophy. Interstitial collagenase may be activated, leading to disruption of the collagen-supporting network. Elongated cells (eccentric hypertrophy), cell slippage, and cell dropout may contribute to the dilatative process. The end product is cardiac dilatation, inefficient left ventricular performance, and congestive heart failure. We have observed that an increase in left ventricular mass is the initial morphological response to acute myocardial damage in a canine model. This occurs at 1 week and is followed by progressive activation of the sympathetic nervous system, left ventricular dilatation, and modest left ventricular dysfunction, a condition that mimics preclinical heart failure in patients. The remodeling process in the canine model, including the increase in mass and volume, may be blocked by angiotensin converting enzyme inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Neurohumoral activation in preclinical heart failure. Remodeling and the potential for intervention. 809 70

While the circulating renin-angiotensin system (RAS) plays an important role in short-term maintenance of cardiovascular homeostasis, recent studies point to a role in long-term cardiovascular regulation for endogenous RAS in target tissues. This article focuses on the multiple effects of tissue angiotensin enzyme (ACE) and angiotensin II (Ang II), its active peptide product. Ang II has been shown to be a potent growth factor in vascular smooth muscle cells. Depending on the local conditions, the vascular response may be either hypertrophy or hyperplasia. The molecular mechanisms involved in the interactions of Ang II with endothelium- and smooth muscle-derived cell products may play important roles in the modulation of vascular structure in hypertension and vascular injury. Evidence also points to a role for Ang II in the development of left ventricular hypertrophy in hypertension. In addition, cardiac RAS may contribute to the pathophysiology of heart failure. Experimental and clinical studies with ACE inhibitors point to a role for tissue ACE activity in the development of atherosclerosis, as well as cardiac hypertrophy and remodeling.
 ...
PMID:Local expression and pathophysiological role of renin-angiotensin in the blood vessels and heart. 839 69

Pharmacokinetic studies are often used to provide additional information regarding the use of pharmacological agents for the treatment of cardiovascular disorders. Pharmacokinetic data are available for the major angiotensin converting enzyme (ACE) inhibitors. However, practical guidelines regarding dosage and dosage intervals are not feasible, and measurements of serum drug concentrations are generally not useful in practice. Such use is obscured by the nature of enzymatic inhibition, renin and angiotensin I accumulation, the complex interaction of several organ systems, the compromise of organ system function due to the heart failure process, the effect of ACE inhibitors on other vasoactive substances and the cellular actions of carboxypeptidase (the enzyme otherwise known as ACE). Pharmacodynamic data demonstrate 2 important factors that influence ACE inhibitor pharmacokinetics and serum concentrations: the aging process and abnormal renal function. As most patients with moderate to severe heart failure have reduced renal function, this has practical implications. Furthermore, heart failure is common in the elderly, and even within the population with heart failure, a superimposed further reduction in renal function can be identified in elderly patients with heart failure. Therefore, a more careful analysis of ACE inhibitor dosage must be made in the presence of decreased renal function and in the elderly patient with heart failure.
 ...
PMID:Optimising ACE inhibitor therapy of congestive heart failure. Insights from pharmacodynamic studies. 844 73


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>