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)

We have previously demonstrated that baroreceptor discharge sensitivity is depressed in dogs with experimental heart failure and that this depressed sensitivity can be reversed by the Na+,K(+)-ATPase inhibitor ouabain. This suggests that enhanced Na+,K(+)-ATPase activity in baroreceptors is responsible for the blunted baroreceptor discharge sensitivity seen in heart failure state. Because aldosterone, a known stimulator of Na+,K(+)-ATPase, is elevated in heart failure the present study was undertaken to determine the effects on baroreceptor discharge of perfusion of the carotid sinus with aldosterone in normotensive dogs. Single unit baroreceptor activity was recorded as well as carotid sinus pressure and the diameter of the carotid sinus. Perfusion of the carotid sinus with aldosterone (in Krebs-Henseleit solution) significantly elevated threshold pressure (108.5 +/- 3.1 mm Hg versus 92.7 +/- 4.6 mm Hg, p less than 0.05) and reduced peak discharge rate (40.3 +/- 3.9 spikes/sec, p less than 0.05). These effects appeared 15 minutes after aldosterone perfusion and remained constant for the next 60 minutes. There was no change in the carotid sinus pressure-diameter curve during perfusion with aldosterone. Perfusion of the carotid sinus with ouabain (0.1 microgram/ml) during aldosterone perfusion did not reverse the blunted baroreceptor discharge. The blunted baroreceptor activity induced by perfusion of the carotid sinus with aldosterone was prevented by removal of the endothelial cells in the carotid sinus area with a balloon-tipped catheter or by perfusion with saponin. Finally, perfusion of the carotid sinus with spironolactone (10 ng/ml), a mineralocorticoid receptor antagonist, prevented the inhibitory effect of aldosterone. These data suggest that aldosterone reduces maximum baroreceptor discharge.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aldosterone reduces baroreceptor discharge in the dog. 154 52

Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are novel natriuretic peptides, originally isolated from porcine brain. Similar to atrial natriuretic peptide (ANP), BNP is also synthesized in and secreted from cardiocytes, but CNP is not expressed at significant levels in normal adult myocardium. Previous studies have indicated that the serum level and ventricular expression of the ANP gene were augmented in patients with heart failure. Recently, the serum level of BNP was also reported to increase in human heart failure. To examine whether or not the expression of these natriuretic peptides is regulated in ventricular myocardium in a concordant manner, we performed Northern blot analysis using total cellular RNA isolated from the diseased left ventricles of 30 cardiac transplant recipients with end-stage heart failure, seven ventricles from organ donors (control group), and two ventricles of artificially aborted 17- and 19-week-old fetuses. The levels of mRNAs encoding both BNP and ANP increased significantly (p less than 0.01) in the left ventricular myocardium from the patients with end-stage heart failure as compared with the control group. The levels of BNP mRNA correlated positively with those of ANP mRNA (r = 0.73, p less than 0.01) and negatively with those of sarcoplasmic reticulum Ca(2+)-ATPase mRNA (r = -0.66, p less than 0.01) in the left ventricular myocardium from the patients with heart failure. There was also a negative correlation between the levels of ANP and the sarcoplasmic reticulum Ca(2+)-ATPase mRNAs (r = -0.65, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles. Correlation with expression of the Ca(2+)-ATPase gene. 153 30

Rats, subsequent to loss of a large amount of left ventricular free wall due to surgically-induced myocardial infarction, form a good model of congestive heart failure. Since depressed cardiac pump function is the hallmark of heart failure, it is suspected that decreased influx of Ca2+ into the cardiac cell is responsible for depressed contractile function. Because Ca2+ movements in the sarcolemmal membrane are known to involve Ca(2+)-channels, Na(+)-Ca2+ exchange, Ca(2+)-pump, Na(+)-K+ ATPase, beta-adrenoceptors and alpha-adrenoceptors directly or indirectly, the status of these mechanisms was examined by employing rats at different degrees of congestive heart failure. The left coronary artery was ligated and hearts were examined 4, 8, and 16 weeks later; sham-operated animals served as controls. The number of Ca2+ channels in the myocardium was depressed in moderate and severe stages of heart failure. Furthermore, depressions in sarcolemmal Na(+)-Ca2+ exchange activity and beta-adrenoceptor number were associated with the development of early stages of heart failure, whereas sarcolemmal Na(+)-K+ ATPase activity was decreased and the number of alpha-adrenoceptors was increased at moderate and severe stages. The Ca(2+)-pump activities were not altered in failing hearts. Thus it appears that changes in Na(+)-Ca2+ exchange as well as beta-adrenoceptors and Ca2+ channels may contribute towards decreasing Ca2+ influx at early and moderate stages of congestive heart failure, respectively. On the other hand, changes in alpha-adrenoceptors and Na(+)-K+ ATPase may act as compensatory mechanisms for maintaining Ca2+ influx at moderate and late stages of congestive heart failure.
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PMID:Experimental congestive heart failure due to myocardial infarction: sarcolemmal receptors and cation transporters. 166 5

We have previously demonstrated that in furazolidone-induced congestive heart failure in turkeys the specific Ca(2+)-ATPase activity of myocardial sarcoplasmic reticulum (SR) is 60% increased in compensation for a 50% depression in net Ca(2+)-sequestration activity. This study tested the hypothesis that SR Ca(2+)-uptake and Ca(2+)-ATPase activities were uncoupled in this cardiomyopathy because of increased Ca(2+)-release channel activity. A novel microassay was used to monitor Ca2+ transport by myocardial homogenates using the fluorescent Ca2+ dye indo 1 to indicate extravesicular ionized Ca2+. The method is applied to cyropreserved biopsy specimens of myocardium and requires only 50 mg tissue. Both SR Ca(2+)-pump and SR Ca(2+)-channel activity were estimated using the channel-inhibitor ruthenium red (RR) and the mitochondrial inhibitor sodium azide. The specificity of the RR inhibition was confirmed using ryanodine. Cardiomyopathy was induced in 2-week-old turkey poults by the addition of 0.07% furazolidone to their feed for 4 weeks. Compared with controls, myocardial maximal Ca(2+)-channel activity relative to maximal Ca(2+)-pump activity was 22% greater and duration of Ca(2+)-channel activity was 100% increased. However, the heart failure birds had 43 and 53% decreases in absolute maximal Ca(2+)-pumping and Ca(2+)-channel activities, respectively. The abnormal Ca(2+)-channel activity resulted in 200% greater time before initiation of net Ca2+ sequestration and 700% greater final myocardial Ca2+ concentrations. For all birds, the Ca(2+)-accumulating activity was highly correlated with Ca(2+)-release activity (all p less than 0.05). These data indicate that in this animal model of congestive heart failure there is defective SR Ca(2+)-channel function resulting in abnormal Ca2+ homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial calcium cycling defect in furazolidone cardiomyopathy. 166 32

Dopamine receptors of DA-1 and DA-2 subtypes are localized in various regions within the kidney including the renal vasculature (DA-1) as well as sympathetic nerve terminals innervating the renal blood vessels (DA-2). More recent studies using receptor-ligand binding and receptor autoradiography have shown that DA-1 receptors are localized at both the luminal and basolateral membranes at the level of the proximal tubules. Activation of these DA-1 receptors by dopamine and by selective DA-1 receptor agonists results in natriuresis and diuresis. The cellular signaling mechanisms responsible for this response appear to be DA-1 receptor-induced activation of adenylate cyclase and phospholipase C, which via the generation of various intracellular messenger systems cause inhibition of Na(+)-H+ antiport (luminal) and Na+, K(+)-ATPase (basolateral), respectively. Both of these events consequently inhibit sodium reabsorption leading to natriuresis and diuresis. It is also known that dopamine can be synthesized within proximal tubular cells from L-dopa, which is taken up from the tubular lumen, and this locally produced dopamine plays an important role in the regulation of sodium excretion particularly during increases in sodium intake. Furthermore, a defect in the renal dopaminergic mechanism may be one of the pathogenic factors in certain forms of hypertension. Finally, whereas DA-1 receptor agonists are shown to be of therapeutic benefit in the treatment of hypertension, heart failure, and acute renal failure, some selective DA-2 receptor agonists are effective antihypertensive agents.
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PMID:Anatomical distribution and function of dopamine receptors in the kidney. 168 44

We investigated the "receptor-effector-coupling" in the beta-adrenoceptor- and the Na+, K(+)-ATPase-mediated systems in nonfailing hearts and terminally failing human myocardium from patients with cardiomyopathy. The density of beta-adrenoceptors in the failing human myocardium was significantly (p less than 0.01) lower as compared with nonfailing hearts, whereas the receptor density and affinity measured by [3H]ouabain binding (cardiac glycoside receptor) was not different in either group. The maximal inotropic response to isoprenaline was significantly reduced in papillary muscle strips from failing human hearts (2.1 +/- 0.5 mN) as compared with control hearts (8.0 +/- 1.0 mN; p less than 0.05). Ouabain remained effective in both groups (6.8 +/- 1.0 vs. 5.5 +/- 0.6 mN; NS). The positive inotropic response due to extracellular Ca2+ elevation (1.8-15 mM) was studied for comparison. Maximal Ca2+ effects were reduced by 30% in failing human myocardium (7.2 +/- 0.5 mN vs. 5.1 +/- 0.8 mN, p less than 0.05). Ouabain had effectiveness (95%) similar to that of Ca2+ in nonfailing and failing human cardiac muscle. It is concluded that treatment with cardiac glycosides may still be effective in end-stage heart failure with "downregulated" beta-adrenoceptors, as judged from these in vitro studies.
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PMID:Effectiveness of cardiac glycosides in human myocardium with and without "downregulated" beta-adrenoceptors. 169 27

The reflex control of the circulation is clearly abnormal in heart failure. It has been known for many years that the baroreflex control of heart rate is depressed in both humans and animals with heart failure. The mechanisms for these abnormalities have not been well worked out. We have carried out experiments to determine the relative roles of the various components involved in the arterial baroreflex arc which may be abnormal in chronic heart failure. An experimental model of chronic heart failure was used which involved continuous ventricular pacing in dogs for periods of up to 6 weeks. This model is characterized by progressive increases in left atrial and left ventricular enddiastolic pressure with increases in resting heart rate and decreases in mean arterial pressure. The dogs become edematous, showing both pulmonary and peripheral edema and ascites. Exercise tolerance is also reduced. Three sets of experiments are described. In the first study, the activity from arterial baroreceptors was recorded in normal dogs and in dogs with heart failure. Carotid sinus pressure-receptor discharge curves were constructed along with pressure-diameter curves. Increasing carotid sinus pressure using either static or pulsatile pressure steps from below threshold to saturation levels caused an increase in discharge at each step. The curves generated in each group of dogs showed that the baroreceptor discharge sensitivity was significantly depressed in the dogs with heart failure. The peak slope of the curves as well as the threshold were significantly different from the normal dogs. There were no differences in carotid sinus compliance curves between the two groups of dogs. Perfusion of the carotid sinus with a dose of ouabain which did not constrict the carotid sinus (0.01 micrograms/ml) caused a shift in the pressure-discharge curve back to that seen in normal dogs. This dose of ouabain did not affect discharge sensitivity in normal dogs. These data suggest that an augmentation of Na-K ATPase in baroreceptor nerve endings in heart failure contributes to the poor discharge sensitivity. In the second series of experiments, the baroreflex control of heart rate was evaluated in dogs before and after heart failure had been induced. Both reflex tachycardia (in response to nitroglycerin) and reflex bradycardia (in response to phenylephrine) were depressed in dogs with heart failure. The use of cholinergic and beta adrenergic blocking drugs indicated that both arms of the autonomic control of the heart were partly responsible for this depressed chronotropic response.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Modulation of baroreflex and baroreceptor function in experimental heart failure. 178 63

To characterize renal transport of Na+ in heart failure, urinary Na+ excretion (UNaV), aldosterone levels, and Na,K-ATPase activity in isolated nephron segments were determined in three groups: control rats, rats with heart failure and moderate sodium retention, and rats with heart failure and severe sodium retention. Heart failure was induced by a fistula between the aorta and vena cava. For the control group, UNaV was 0.66 +/- 0.04 (mean +/- SEM) mueq/min, and aldosterone was 18.4 +/- 3.5 ng%. Na,K-ATPase activity (in 10(-11) mol/mm/min) was 28.4 +/- 1.1 in the proximal convoluted tubule, 23.3 +/- 1.0 in the proximal straight tubule, 37.4 +/- 1.9 in the medullary thick ascending limb, 40.2 +/- 1.9 in the cortical thick ascending limb, 43.2 +/- 2.2 in the distal convoluted tubule, and 20.5 +/- 0.9 in the cortical collecting duct. For the group with moderate heart failure, UNaV was 0.35 +/- 0.02 (p less than 0.001 versus control), and aldosterone was 15.9 +/- 4.4 (p = NS versus control). Na,K-ATPase activity was unchanged in the proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb, and cortical collecting duct, but it increased in the cortical thick ascending limb to 57.7 +/- 3.1 (p less than 0.001 versus control) and decreased in the distal convoluted tubule to 35.3 +/- 1.2 (p less than 0.005 versus control). For the group with severe heart failure, UNaV was 0.029 +/- 0.016 (p less than 0.001 versus control), and aldosterone was 186.0 +/- 14.8 (p less than 0.001 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Na,K-ATPase in isolated nephron segments in rats with experimental heart failure. 184 57

Advances in regulation by secondary messengers of Ca2+ level in cardiomyocyte and vascular smooth muscle cell cytosols with special reference to the major differences in regulatory effects in cells of the both types are reviewed. The effects of cAMP, cGMP, Ca2+, calmodulin, diacylglycerol and polyphosphoinositides on the Ca(2+)-channel, Ca(2+)-ATPase, plasmalemma, sarcoplasmic reticulum and outer membrane Na+/Ca2+ uniporter function are considered. Compartmentation of secondary messengers and protein kinase in cardiac and vascular smooth muscle cells should be taken into consideration during extrapolation of in vitro data to an in situ situation. The feasible role of impaired phosphorylation of membrane-bound proteins of cardiac and vascular smooth muscle cells in cardiac insufficiency and atherosclerosis is discussed.
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PMID:[Second messengers in heart cells and smooth muscle vessels]. 191 66

The expression of troponin (Tn) T, a thin-filament regulatory protein, was examined in left ventricular myocardium from normal and from failing adult human hearts. The differences in isoform expression between normal and failing myocardium led us to examine the ontogenic expression of TnT in human striated muscle. Left ventricular samples were obtained from patients with severe heart failure undergoing cardiac transplantation and normal adult organ donors. Fetal muscle was obtained from aborted fetuses after 14-15 weeks of gestation, and adult skeletal muscle was obtained from surgical biopsies. Western blots of normal and failing adult heart proteins demonstrated that two isoforms, TnT1 and TnT2, are expressed in different amounts, with TnT2 being significantly greater in failing hearts (p less than 0.004). Western blots of two-dimensional gels of these proteins resolved two predominant spots of both TnT1 and TnT2 and several minor TnT species. Alkaline phosphatase treatment converted the two major spots of each isoform into the single more basic spots. A comparison of the ATPase activities and the TnT2 percentage of total TnT in individual failing and normal adult hearts demonstrated an inverse and negative relation (r = 0.7, p less than 0.02). In the fetal heart, four TnT isoforms were found, two of which had the same electrophoretic mobilities as the adult cardiac isoforms TnT1 and TnT2. Fetal skeletal muscle expressed two of the four fetal cardiac TnT isoforms, one of which comigrated with adult cardiac TnT1. These cardiac isoforms were expressed in low abundance in fetal skeletal muscle relative to seven fast skeletal muscle TnT isoforms. No cardiac isoforms were present in adult skeletal muscle. Because many etiologies caused heart failure in the transplant patients, we propose that the disease-associated increased expression of the TnT isoform TnT2 is an adaptation to the heart failure state and a partial recapitulation of the fetal expression of cardiac TnT isoforms.
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PMID:Troponin T isoform expression in humans. A comparison among normal and failing adult heart, fetal heart, and adult and fetal skeletal muscle. 193 53


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