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)

Na+/K(+)-ATPase of the cell membrane is considered to be closely related to the pathology of various diseases including hypertension and heart failure. The activity of this enzyme in the erythrocyte membrane has been determined in earlier reports by the assay of inorganic phosphate generated from the substrate ATP or radioimmunoassay after binding 3H ouabain to the erythrocyte membrane, using a large volume of blood samples. However, as neither method was appropriate for wide routine use, we developed a method to assay this enzyme in a small volume (10 ml) of fresh human blood samples with re-evaluation of conditions for the inorganic phosphate assay. In this method, the coefficient value (CV) of membrane protein amount and the NA+/K(+)-ATPase activity were 2.2% and 2.5% respectively, indicating sufficient precision of the assay. Moreover, in 97 subjects without abnormalities in blood biochemical tests (77 males and 20 females) aged 35-59 years, the enzyme activity showed no differences according to age or sex, ranging from 0.217 to 0.071 mumols Pi/mg/hr with a mean of 0.130.
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PMID:[Determination of human erythrocyte membrane Na+/K(+)-ATPase activity in small volume of blood sample]. 131 73

The present study investigated whether reduced adenylate cyclase activity and an increase in inhibitory guanine nucleotide binding proteins (Gi alpha), which have been observed in the failing human heart, already occur in myocardial hypertrophy before the stage of heart failure. In membranes of hypertrophic hearts from rats with different forms of experimentally induced hypertension without heart failure (one-kidney, one clip rats, deoxycorticosterone-treated rats, and rats with reduced renal mass), basal as well as isoprenaline-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylate cyclase activity was reduced. The activity of the catalyst was depressed in deoxycorticosterone but unchanged in one-kidney, one clip and reduced renal mass compared with controls. The number of beta-adrenergic receptors was similar in all groups. Radioimmunological quantification of Gi alpha proteins revealed an increase by 73% in one-kidney, one clip, 67% in reduced renal mass, but only 20% in deoxycorticosterone compared with sham-operated, age-matched control rats. The increase of Gi alpha was accompanied by smaller changes of pertussis toxin-induced [32P]ADP-ribosylation of a 40-kd membrane protein. It is concluded that Gi alpha contributes to the reduced adenylate cyclase activity in cardiac hypertrophy in one-kidney, one clip and reduced renal mass and to a smaller extent in deoxycorticosterone. It is suggested that an enhanced expression of Gi alpha could occur not only in severe heart failure but also in cardiac hypertrophy and could, therefore, contribute to myocardial depression and progression of disease in heart failure. In addition, Gi alpha might represent an important regulatory mechanism for cardiac adenylate cyclase activity and thus, might play an important role in various cardiac diseases.
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PMID:Desensitization of adenylate cyclase and increase of Gi alpha in cardiac hypertrophy due to acquired hypertension. 131 58

Severe decompensated chronic heart failure is associated to increased levels of circulating catecholamines and decreased density of myocardial beta-adrenergic receptors. In 14 patients with stable, class II-III heart failure we studied circulating lymphocytes to determine the number of beta adrenergic receptors, the dissociation constant of 3H dihydroalprenolol (kd) and the intracellular content of cyclic AMP (AMPc). Results (mean +/- SEM) were compared to those obtained in 10 healthy controls. The number of beta receptors was significantly decreased (105 +/- 16 vs 185 +/- 24, fmol/mg of membrane protein, p less than 0.01). No differences were found in Kd (1.65 +/- 0.2 vs. 1.36 +/- 0.28 nm) nor the level of AMPc (7.9 +/- 2.1 vs 7.1 +/- 2.9 pmol/mg protein), respectively. The decreased number of beta adrenergic receptors in the circulating lymphocytes may be related to the increased level of circulating catecholamines that have been shown to be present during exercise in these patients.
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PMID:[Beta adrenergic receptors in circulating lymphocytes of patients with chronic heart failure]. 166 48

1. Myocardial beta-adrenoreceptors, assessed in membrane preparations of left ventricle by 3H-dihydroalprenolol binding, were compared in dogs following thyroxine administration (n = 6), aorto-caval fistula (n = 12), and in normal dogs (n = 7). 2. Left ventricular hypertrophy occurred in response to both aorto-caval fistula and thyroxine treatment. Yield of myocardial membrane between the different groups was not significantly different. 3. Binding site concentration (pmol/mg membrane protein) in dogs with aorto-caval fistulae was similar to that in normal dogs and was not significantly influenced by the presence or absence of cardiac failure, degree of hypertrophy or duration of fistula. 4. Thyroxine-treated dogs had an increased concentration of binding sites (c. 1.8-fold) compared with both fistula and normal groups, while binding affinities were similar in all groups. 5. The data suggest that beta-adrenoreceptor concentrations in myocardium increase as a direct result of thyroid hormone action rather than as a result of secondary haemodynamic changes or ventricular hypertrophy.
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PMID:Cardiac beta-adrenoreceptors in the thyroxine-treated dog. 626 26

The inotropic responsiveness to adrenergic stimulation is diminished in hypertension associated with left ventricular hypertrophy (LVH). This was shown in hypertrophied hearts from renal hypertensive rats (RHR) (two-kidney, one clip hypertension, Goldblatt) 6 weeks after renal artery clipping when compared to age-matched normotensive sham-operated controls (NR). The isoproterenol-stimulated inotropic responses (delta peak dP/dt) of isolated hearts perfused at constant pressure were significantly lower in RHR than in NR (p less than 0.001 by analysis of variance and covariance, including repeated measures). This reduction in ventricular responsiveness of isolated hearts from RHR did not extend to other inotropic agents such as calcium ions and the cardiotonic cardiac glycoside scillaren. Assay of beta-adrenergic receptors by binding to (-) [3H] dihydroalprenolol showed that left ventricular beta-receptor numbers (fmol per mg membrane protein) were significantly reduced in RHR compared to NR (28.2 +/- 1.1 vs 36 +/- 2.6, p less than 0.01) with no significant change in affinity (Kd,nM) (1.9 +/- 0.27 vs 2.26 +/- 0.34,NS). The results of this study suggest that LVH in renovascular hypertension is associated with impairment in inotropic responsiveness to beta-receptor stimulation parallel with and, in part, related to, a reduction in ventricular beta-receptor concentrations. Such blunting of inotropic responsiveness to beta-adrenergic stimulation may be one of the mechanisms in the progression from LVH to heart failure in hypertensive disease.
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PMID:beta-Receptors and contractile reserve in left ventricular hypertrophy. 629 4

Platelet number and alpha-granule membrane protein (GMP-140) level on platelet surface were determined in 20 patients with acute myocardial infarction (AMI) and 20 normal subjects. The results showed that platelet number decreased significantly after AMI, especially on the second day after onset and that the level of GMP-140 increased rapidly after AMI and reached a peak on the second after the attack. Both returned to the normal on the 5-7th day after the heart attack. Correlative analysis between increase of serum CK-MB and platelet number was negative (r = -0.6123, P < 0.005), and positive between that and GMP-140 level (r = 0.5895, P < 0.01). Platelet number decreased markedly in cases with heart failure and cardiac death. The results indicate that platelets are involved in the pathological process of AMI.
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PMID:[The change of platelet number in patient with acute myocardial infarction and its clinical significance]. 754 27

An increase of Gi alpha-related pertussis toxin substrates has been observed in the failing myocardium. In order to quantify the protein expression of Gi alpha directly, we developed a fast radioimmunoassay using the iodinated synthetic peptide 125I-KENLKDCGLF. beta-adrenoceptors were studied with 125I-cyanopindolol binding for comparison. Immunoblot experiments using recombinant G-protein alpha-subunits showed that DS4 immunostained the G-protein alpha-subunits with a rank order of potency rGi alpha 1 = rGi alpha 2 > rGo alpha >> rGi alpha 3. The G-protein alpha-subunits recognized by DS4 in human ventricular membranes comigrated with rGi alpha 1 and rGi alpha 2. The radioimmunoassay had a sensitivity of 2.5 micrograms/ml transducin alpha with an interassay variation of less than 10%. The non-labelled peptide selectively competed with the myocardial 40 kDa membrane protein for binding to the antiserum DS4. Radioimmunochemical quantification of Gi alpha from cardiac membranes showed that in left ventricular membranes (LV) from dilated cardiomyopathy (DCM), there was an increase of Gi alpha by 138.5% when related to mg protein and 135% when related to 3H-ouabain binding sites as membrane marker. In LV from ischaemic cardiomyopathy (ICM), the increase was smaller (58.4%) when related to mg protein compared to the increase of Gi alpha when related to 3H-ouabain binding sites as membrane marker (155% v NF). In contrast, in the right ventricles (RV) there was no increase of Gi alpha in ICM or DCM. The numbers of beta-adrenoceptors were reduced in RV and LV of both, ICM and DCM. It is concluded that the radioimmunoassay may become an important tool for studying the expression of Gi alpha-protein levels and changes thereof in pathological conditions. The amount of immunodetectable Gi alpha-proteins is increased in failing LV due to DCM and ICM but not in RV, while beta-adrenoceptor down-regulation occurred in RV and LV in both conditions. These findings might indicate that the liability of the LV but not of RV to express Gi alpha-proteins may be increased in predominant LV heart failure. Alternatively, the underlying mechanism, e.g. sympathetic activation, may be regulated locally in the failing heart producing different changes in adjacent chambers.
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PMID:Radioimmunochemical quantification of Gi alpha in right and left ventricles from patients with ischaemic and dilated cardiomyopathy and predominant left ventricular failure. 800 75

We recently demonstrated that rapid ventricular pacing caused cardiac failure (Failure) in dogs with aortic stenosis-induced left ventricular hypertrophy (Hypertrophy) and isoproterenol caused no significant increases in function, O2 consumption and intracellular cyclic AMP level in the failing hypertrophied hearts. We tested the hypothesis that alterations in the beta1-adrenoceptor-signal transduction pathway would correlate with the reduced functional and metabolic responses to beta-adrenergic stimulation during the transition from the compensated hypertrophy to failure. Pressure overload-induced left ventricular hypertrophy was created using aortic valve plication in 10 dogs over a 6-month period. Five months after aortic valve plication, congestive heart failure was induced in 5 dogs by rapid ventricular pacing at 240 bpm for 4 weeks. The density of myocardial beta1-adrenoceptors (fmoles/mg membrane protein; fmoles/g wet tissue) was significantly reduced in the Failure dogs (176+/-19; 755+/-136) when compared to those of the Control (344+/-51; 1,551+/-203) and the Hypertrophy (298+/-33; 1,721+/-162) dogs. The receptor affinities were not significantly different among all groups. There was a small but significant decrease in the percentage of beta1-adrenoceptors of the failing hypertrophied hearts (62+/-3%) when compared to that of the hypertrophied hearts (77+/-5%). The basal myocardial adenylyl cyclase activity (pmoles/mg protein/min) was significantly lower in the Failure dogs (45+/-4) than in the Control (116+/-14) and Hypertrophy (86+/-6) dogs. The forskolin (0.1 mM)-stimulated adenylyl cyclase activity was also significantly lower in the Failure dogs (158+/-17) than in the Control dogs (296+/-35) and slightly lower than in the Hypertrophy dogs (215+/-10). There were no significant differences in low Km cyclic AMP-phosphodiesterase activities among all groups. We conclude that down regulation of beta1-adrenoceptors and reduced adenylyl cyclase activities contribute to the decreases in myocardial functions and beta-adrenergic responses in the failing hypertrophied hearts induced by rapid ventricular pacing.
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PMID:Down regulation of myocardial beta1-adrenoceptor signal transduction system in pacing-induced failure in dogs with aortic stenosis-induced left ventricular hypertrophy. 1082 23

We identified abnormalities in the vascular beta-adrenergic receptor (beta-AR) signaling pathway in heart failure after myocardial infarction (MI). To examine these abnormalities, we measured beta-AR-mediated hemodynamics, vascular reactivity, and the vascular beta-AR molecular signaling components in rats with heart failure after MI. Six weeks after MI, these rats had an increased left ventricular (LV) end-diastolic pressure, decreased LV systolic pressure, and decreased rate of LV pressure change (dP/dt). LV dP/dt responses to isoproterenol were shifted downward, although the responses for systemic vascular resistance were shifted upward in heart failure rats (P < 0.05). Isoproterenol- and IBMX-induced vasorelaxations were blunted in heart failure rats (P < 0.05) with no change in the forskolin-mediated vasorelaxation. These changes were associated with the following alterations in beta-AR signaling (P < 0.05): decreases in beta-AR density (aorta: 58.7 +/- 6.0 vs. 35.7 +/- 1.9 fmol/mg membrane protein; carotid: 29.6 +/- 5.6 vs. 18.0 +/- 3.9 fmol/mg membrane protein, n = 5), increases in G protein-coupled receptor kinase activity levels (relative phosphorimage counts of 191 +/- 39 vs. 259 +/- 26 in the aorta and 115 +/- 30 vs. 202 +/- 7 in the carotid artery, n = 5), and decreases in cGMP and cAMP in the carotid artery (0.85 +/- 0.10 vs. 0.31 +/- 0.06 pmol/mg protein and 2.3 +/- 0.3 vs. 1.2 +/- 0.1 pmol/mg protein, n = 5) with no change in Galpha(s) or Galpha(i )in the aorta. Thus in heart failure there are abnormalities in the vascular beta-AR system that are similar to those seen in the myocardium. This suggests a common neurohormonal mechanism and raises the possibility that treatment in heart failure focused on the myocardium may also affect the vasculature.
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PMID:Vascular beta-adrenergic receptor system is dysfunctional after myocardial infarction. 1117 56

ATP-sensitive potassium (K(ATP)) channels are evolutionarily conserved plasma-membrane protein complexes, widely represented in tissue beds with high metabolic activity. There, they are formed through physical association of the inwardly rectifying potassium channel pore, most typically Kir6.2, and the regulatory sulfonylurea receptor subunit, an ATP-binding cassette protein. Energetic signals, received via tight integration with cellular metabolic pathways, are processed by the sulfonylurea receptor subunit that in turn gates the nucleotide sensitivity of the channel pore thereby controlling membrane potential dependent cellular functions. Recent findings, elicited from genetic disruption of channel proteins, have established in vivo the requirement of intact K(ATP) channels in the proper function of cardiac muscle under stress. In the heart, where K(ATP) channels were originally discovered, channel ablation compromises cardioprotection under ischemic insult. New data implicate the requirement of intact K(ATP) channels for the cardiac adaptive response to acute stress. K(ATP) channels have been further implicated in the adaptive cardiac response to chronic (patho)physiologic hemodynamic load, with K(ATP) channel deficiency affecting structural remodeling, rendering the heart vulnerable to calcium-dependent maladaptation and predisposing to heart failure. These findings are underscored by the identification in humans that defective K(ATP) channels induced by mutations in ABCC9, the gene encoding the cardiac sulfonylurea receptor subunit, confer susceptibility to dilated cardiomyopathy. Thus, in parallel with the developed understanding of the molecular identity and mode of action of K(ATP) channels since their discovery, there is now an expanded understanding of their critical significance in the cardiac stress response in health and disease.
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PMID:Cardiac KATP channels in health and disease. 1591 Aug 78


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