Abstract:
:We compared the effects of the newer inotropic drugs, pimobendan (UD-CG 115 BS) and milrinone (Win 47203), on the electrical, mechanical and biochemical activity of intact and detergent-skinned preparations of cardiac muscle. Both of these agents increased contractile force of guinea pig papillary muscle preparations bathed under physiological conditions or depolarized with 25 mM K+o. The positive inotropic action was associated with potentiation of the Ca2+-dependent slow action potentials (APS). Contractile force developed in the presence of 25 mM [K]o and 1 microM isoproterenol was increased further by addition of 50 microM pimobendan with no effect on the slow action potential. Milrinone (50 microM) did not produce a further increase in the force or potentiate the slow APs. Pimobendan, in a dose-dependent manner, increased active tension developed by chemically-skinned dog heart muscle fibers at submaximally activating concentrations of Ca2+, whereas milrinone did not. At pCa 6.25, the half-maximal concentration of pimobendan for stimulation of force development was about 40 microM. At maximally activating levels of Ca2+ (pCa 4.5), pimobendan had little or no effect on force development. The effect of pimobendan on force was paralleled by changes in the Ca2+-activated Mg-ATPase activity of the isometric skinned fiber preparations. Moreover, the tension-cost (unit increase in ATPase rate/unit increase in force) was unchanged in the presence of pimobendan. Milrinone did not affect ATP hydrolysis by the skinned fiber preparations. Force-pCa and ATPase-pCa relations of skinned fiber preparations contracting isometrically were shifted to the left by 0.15-0.20 pCa units in the presence of 50 microM pimobendan. In contrast, there was no effect of pimobendan on the ATPase activity of unloaded myofibrillar preparations. The stimulation of force and ATPase activity of the skinned heart muscle fibers could be accounted for by an effect of pimobendan on the affinity of the regulatory (low affinity, Ca2+-specific) binding sites of cardiac troponin C. Ca2+ binding to the "structural" high affinity sites of troponin C was slightly inhibited. The results indicate that the positive inotropic actions of pimobendan, but not milrinone, may involve activation of the cardiac myofilaments by a direct effect involving an increased affinity of the regulatory site on troponin C for Ca2+.
journal_name
Circ Resjournal_title
Circulation researchauthors
Fujino K,Sperelakis N,Solaro RJdoi
10.1161/01.res.63.5.911subject
Has Abstractpub_date
1988-11-01 00:00:00pages
911-22issue
5eissn
0009-7330issn
1524-4571journal_volume
63pub_type
杂志文章abstract::Cardiac hemodynamics, diameter, blood flow velocity, and volumic flow of the brachial artery were studied before and after diltiazem administration in 11 patients with sustained essential hypertension. The study was compared with the hemodynamic effects of dihydralazine. The caliber of the brachial artery was evaluate...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract:RATIONALE:Prospective cohort studies question the value of HDL-C (high-density lipoprotein cholesterol) for stroke risk prediction. OBJECTIVE:Investigate the relationship between long-term functional recovery and HDL proteome and function. METHODS AND RESULTS:Changes in HDL protein composition and function (cholester...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.316526
更新日期:2020-10-23 00:00:00
abstract:RATIONALE:Shear stress (SS) has an established role in atherosclerotic plaque localization, but how it exerts its protective effect is not fully understood. OBJECTIVE:To test the hypothesis that SS may downregulate angiotensin type 1 receptors (AT(1)Rs). Angiotensin II has been shown to be proinflammatory and to promo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.204040
更新日期:2009-10-23 00:00:00
abstract::We studied the effects of intense sympathetic stimulation on the chronotropic responses of the heart to subsequent test stimulations of the cardiac autonomic nerves in dogs anesthetized with alpha-chloralose. Such intense sympathetic stimulations (which we refer to as "release stimulations") are known to release neuro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.1.137
更新日期:1993-01-01 00:00:00
abstract::14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Targeted expression of dominant-negative 14-3-3eta (DN-14-3-3) to murine postnatal cardiac tissue potentiates Ask1, c-jun N-terminal kinase (JNK), and p38 mitogen-activated pr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000104084.88317.91
更新日期:2003-11-28 00:00:00
abstract::Nitrite has recently emerged as an important bioactive molecule, capable of conferring cardioprotection and a variety of other benefits in the cardiovascular system and elsewhere. The mechanisms by which it accomplishes these functions remain largely unclear. To characterize the dose response and corresponding cardiac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.187005
更新日期:2009-03-27 00:00:00
abstract::We determined the effects of changing the spatial dispersion of acetylcholine release on the phase-dependent chronotropic responses to vagal stimulation in anesthetized dogs. We stimulated the vagus nerves with one brief burst of electrical pulses each cardiac cycle, and we changed the timing of the stimulus by a smal...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.4.844
更新日期:1990-10-01 00:00:00
abstract::Insulin-like growth factor-I (IGF-I) plays an important role in regulating vascular smooth muscle cell (VSMC) proliferation and directed migration. The mitogenic and chemotactic actions of IGF-I are mediated through the IGF-I receptor, but how the activation of the IGF-I receptor leads to these biological responses is...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.1.15
更新日期:2000-01-07 00:00:00
abstract::Previously, it was shown that the D enantiomer of isoidide dinitrate was 10-fold more potent than the L enantiomer and 10-fold less potent than glyceryl trinitrate for stimulating cyclic GMP accumulation and relaxation of isolated rat aorta. In the present study, these organic nitrates were tested for their ability to...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.4.693
更新日期:1988-10-01 00:00:00
abstract::Alveolar epithelial beta-adrenergic receptor (betaAR) activation accelerates active Na+ transport in lung epithelial cells in vitro and speeds alveolar edema resolution in human lung tissue and normal and injured animal lungs. Whether these receptors are essential for alveolar fluid clearance (AFC) or if other mechani...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000125623.56442.20
更新日期:2004-04-30 00:00:00
abstract:RATIONALE:Cardiac myosin-binding protein-C (cMyBP-C) phosphorylation at Ser-273, Ser-282, and Ser-302 regulates myocardial contractility. In vitro and in vivo experiments suggest the nonequivalence of these sites and the potential importance of Ser-282 phosphorylation in modulating the protein's overall phosphorylation...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.242560
更新日期:2011-07-08 00:00:00
abstract:RATIONALE:The recent discovery of meningeal lymphatics in mammals is reshaping our understanding of fluid homeostasis and cellular waste management in the brain, but visualization and experimental analysis of these vessels is challenging in mammals. Although the optical clarity and experimental advantages of zebrafish ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.317372
更新日期:2021-01-08 00:00:00
abstract::The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV nodal myocardium-specific reporter mouse to gain insight into the gene programs determining the formation an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.192443
更新日期:2009-07-02 00:00:00
abstract::Trimetazidine is a clinically effective antianginal agent that has no negative inotropic or vasodilator properties. Although it is thought to have direct cytoprotective actions on the myocardium, the mechanism(s) by which this occurs is as yet undefined. In this study, we determined what effects trimetazidine has on b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.5.580
更新日期:2000-03-17 00:00:00
abstract:RATIONALE:Clinical studies have shown that Sirt3 (Sirtuin 3) expression declines by 40% by 65 years of age paralleling the increased incidence of hypertension and metabolic conditions further inactivate Sirt3 because of increased NADH (nicotinamide adenine dinucleotide, reduced form) and acetyl-CoA levels. Sirt3 impair...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.310933
更新日期:2017-08-18 00:00:00
abstract:RATIONALE:Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies ha...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.270132
更新日期:2012-09-28 00:00:00
abstract::Cell-cell communication has proven to be even more complex than previously thought since the discovery that extracellular vesicles serve as containers of biological information on various pathophysiological settings. Extracellular vesicles are classified into exosomes, microvesicles/microparticles, or apoptotic bodies...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300858
更新日期:2014-01-17 00:00:00
abstract::Cyclic nucleotides are known to modify voltage-gated (L-type) Ca2+ channel activity in vascular smooth muscle cells, but the exact mechanism(s) underlying these effects is not well defined. The purpose of the present study was to investigate the modulatory role of the cAMP- and cGMP-dependent protein kinase (PKA and P...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.5.557
更新日期:1998-03-23 00:00:00
abstract::Transmembrane potentials, extracellular potassium activity, and intracellular sodium activity were determined during acute global ischemia in Langendorff perfused guinea pig ventricles by microelectrode techniques. Resting membrane potential decreased with a sigmoidal time course from -82 mV to -49.5 +/- 2.7 mV (SD, n...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.4.442
更新日期:1983-04-01 00:00:00
abstract::The ionic currents that cross the myocardial membrane during cardiac activation have a corresponding return path in the extracellular space. The transmembrane current (Im) during activation of cardiac cells in situ has previously been envisioned only in mathematical models. We have developed a remarkably simple in viv...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.2.424
更新日期:1993-02-01 00:00:00
abstract::The red cell membrane is a permeability barrier that limits the equilibration of a variety of solutes between red cell and plasma water. We utilized the multiple indicator dilution technique to investigate the effect of this barrier on the exchange in the liver of a group of tracer substances that are not removed in n...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.2.328
更新日期:1975-02-01 00:00:00
abstract::Sixty-eight blood pressure (BP)-lowering randomized controlled trials (defined as randomized controlled trials comparing active treatment with placebo, or less active treatment, achieving a BP difference, performed between 1966 and end 2013 in cohorts with ≥ 40% hypertensive patients, and exclusive of trials in acute ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.303641
更新日期:2015-03-13 00:00:00
abstract::Direct binding of apolipoprotein (apo)B-containing lipoproteins to proteoglycans is the initiating event in atherosclerosis, but the processes involved at later stages of development are unclear. Here, we investigated the importance of the apoB-proteoglycan interaction in the development of atherosclerosis over time a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.149666
更新日期:2007-10-12 00:00:00
abstract:RATIONALE:Oxidative stress is an important contributing factor in several human pathologies ranging from atherosclerosis to cancer progression; however, the mechanisms underlying tissue protection from oxidation products are poorly understood. Oxidation of membrane phospholipids, containing the polyunsaturated fatty ac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.305925
更新日期:2015-07-31 00:00:00
abstract::Electrotonic coupling of cardiac myocytes at gap junctions may influence patterns of conduction in myocardium. To delineate the three-dimensional structure and distribution of intercellular junctions, we analyzed serial ultrathin sections of canine myocardium with transmission electron microscopy and disaggregated myo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.3.563
更新日期:1989-03-01 00:00:00
abstract::Electrical field stimulation (EFS) of phenylephrine-contracted bovine mesenteric arteries pretreated with guanethidine elicited a relaxation that amounted to roughly 40%. This relaxation was sensitive to tetrodotoxin pretreatment, suggesting a neurogenic origin. The EFS-induced relaxation was correlated to an increase...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.3.756
更新日期:1991-03-01 00:00:00
abstract::The purpose of this study was to explore the changes in fetal blood volume that occur after fetal hemorrhage. Fifteen unanesthetized, chronically catheterized fetal sheep averaging 130 +/- 3 (SD) days gestation were studied 4 to 6 (average 5) days after catheter implantation. The fetuses were hemorrhaged by continuous...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.6.730
更新日期:1983-06-01 00:00:00
abstract::We investigated expression of the 5'-spliced isoform of smooth muscle myosin heavy chain (SM-MHC-B) in smooth muscle cells of cardiac vessels of the left ventricle of normotensive (Wistar-Kyoto) and spontaneously hypertensive rats of the stroke-prone strain by immunofluorescence microscopy. In parallel, liver and blad...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.2.204
更新日期:1998-07-27 00:00:00
abstract::Transcriptional thyroid hormone responsiveness of the cardiac alpha-myosin heavy chain (alpha-MHC) gene has been demonstrated in transfections into fetal and neonatal cardiomyocytes and in transgenic mice. However, the correspondence between the regulation of MHC expression in dissociated cells with that in the intact...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.6.1211
更新日期:1993-06-01 00:00:00
abstract::The use of risk markers has transformed cardiovascular medicine, exemplified by the routine assessment of troponin, for both diagnosis and assessment of prognosis in patients with chest pain. Clinical risk factors form the basis for risk assessment of cardiovascular disease and the addition of biochemical, cellular, a...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.309955
更新日期:2017-01-06 00:00:00