Involvement of vitamin D3 with cardiovascular function. II. Direct and indirect effects

1987 ◽  
Vol 253 (6) ◽  
pp. E675-E683 ◽  
Author(s):  
R. E. Weishaar ◽  
R. U. Simpson
Keyword(s):  
Serum Calcium ◽  
Vitamin D3 ◽  
Contractile Function ◽  
Initial Period ◽  
Cardiovascular Function ◽  
Cardiac Contractile Function ◽  
Deficient Diet ◽  
Cardiac Contractile ◽  
Vitamin D3 Deficiency

To determine whether the changes in cardiovascular function that accompany vitamin D3 deficiency are the direct result of hypovitaminosis D3 or a response to the hypocalcemia that accompanies vitamin D3 deficiency, rats were maintained for 9 wk on a vitamin D3-deficient diet containing either low (0.4%) calcium or high (2.5%) calcium to prevent hypocalcemia. Rats were also maintained on the low-calcium, vitamin D3-deficient diet for 9 wk and then transferred to diets designed to reverse hypocalcemia or vitamin D3 deficiency. The results demonstrate that the changes in in vitro cardiac contractile function that accompany vitamin D3 deficiency 1) could not be prevented by preventing the hypocalcemia that normally accompanies vitamin D3 depletion or 2) could not be reversed by restoration of serum calcium to normal levels after the initial period of vitamin D3 depletion. In contrast, the change in in vitro vascular muscle contractile function observed in vitamin D3-deficient, hypocalcemic rats could be prevented by maintaining serum calcium at normal levels and also reversed by restoration of serum calcium to normal after an initial period of vitamin D3 deficiency. These observations indicate that hypocalcemia does not account for the changes in cardiac contractile function that result from vitamin D3 depletion and suggest a direct role for vitamin D3 or its metabolite 1,25-dihydroxyvitamin D3 in regulating cardiac contractility. Possible mechanisms underlying this direct effect were also explored.

Lipid peroxidation contributes to cardiac deficits after ischemia and reperfusion of the small bowel

1993 ◽  
Vol 264 (5) ◽  
pp. H1686-H1692 ◽  
Author(s):  
J. W. Horton ◽  
D. J. White
Keyword(s):  
Lipid Peroxidation ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Contractile Function ◽  
Langendorff Preparation ◽  
Cardiac Contractile ◽  
Intestinal Ischemia Reperfusion

Our previous studies showed that intestinal ischemia-reperfusion (IR) impairs cardiac contractile function. The present study examined the contribution of oxygen free radicals and lipid peroxidation of cardiac cell membrane to cardiac dysfunction after intestinal IR in a rat model of superior mesenteric artery (SMA) occlusion (atraumatic clip for 20 min) and collateral arcade ligation. Controls were sham operated (group 1, n = 25). In group 2, 30 rats with SMA occlusion were killed 3-4 h after reperfusion without treatment. Aminosteroid (U-74389F), a pharmacological agent known to inhibit lipid peroxidation of membranes, was given 1 min before occlusion of the SMA (group 3, n = 19). All rats were killed 3-4 h after reperfusion of the ischemic intestine, and the hearts were harvested for in vitro assessment of cardiac function (Langendorff preparation). Cardiac contractile depression occurred in the untreated group as indicated by a fall in left ventricular pressure (from 76 +/- 3 to 64 +/- 3 mmHg, P = 0.01), maximum +dP/dt (from 1,830 +/- 60 to 1,577 +/- 64 mmHg/s, P = 0.05), and maximum -dP/dt (from 1,260 +/- 50 to 950 +/- 60 mmHg/s, P = 0.005). Lipid peroxidation of cardiac membranes occurred after untreated IR as indicated by the rise in cardiac malondialdehyde levels (MDA) (from 0.203 +/- 0.046 to 0.501 +/- 0.044 nM/mg protein, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Taxol, a Microtubule Stabilizer, Improves Cardiac Contractile Function during Ischemia in vitro

Pharmacology ◽  
2010 ◽  
Vol 85 (5) ◽  
pp. 301-310 ◽  
Author(s):  
Junjie Xiao ◽  
Hong Zhao ◽  
Dandan Liang ◽  
Ying Liu ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Contractile Function ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Microtubule Stabilizer

scholarly journals Organization of β-adrenoceptor signaling compartments by sympathetic innervation of cardiac myocytes

2007 ◽  
Vol 176 (4) ◽  
pp. 521-533 ◽  
Author(s):  
Olga G. Shcherbakova ◽  
Carl M. Hurt ◽  
Yang Xiang ◽  
Mark L. Dell'Acqua ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Myocytes ◽  
Contractile Function ◽  
Sympathetic Neurons ◽  
Sympathetic Innervation ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Specific Regulation

The sympathetic nervous system regulates cardiac function through the activation of adrenergic receptors (ARs). β1 and β2ARs are the primary sympathetic receptors in the heart and play different roles in regulating cardiac contractile function and remodeling in response to injury. In this study, we examine the targeting and trafficking of β1 and β2ARs at cardiac sympathetic synapses in vitro. Sympathetic neurons form functional synapses with neonatal cardiac myocytes in culture. The myocyte membrane develops into specialized zones that surround contacting axons and contain accumulations of the scaffold proteins SAP97 and AKAP79/150 but are deficient in caveolin-3. The β1ARs are enriched within these zones, whereas β2ARs are excluded from them after stimulation of neuronal activity. The results indicate that specialized signaling domains are organized in cardiac myocytes at sites of contact with sympathetic neurons and that these domains are likely to play a role in the subtype-specific regulation of cardiac function by β1 and β2ARs in vivo.

scholarly journals FTO-Dependent N 6 -Methyladenosine Regulates Cardiac Function During Remodeling and Repair

Circulation ◽  
2019 ◽  
Vol 139 (4) ◽  
pp. 518-532 ◽  
Author(s):  
Prabhu Mathiyalagan ◽  
Marta Adamiak ◽  
Joshua Mayourian ◽  
Yassine Sassi ◽  
Yaxuan Liang ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Mouse Models ◽  
Contractile Function ◽  
Cardiac Contraction ◽  
Functional Importance ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Rna Immunoprecipitation

Background: Despite its functional importance in various fundamental bioprocesses, studies of N 6 -methyladenosine (m6A) in the heart are lacking. Here, we show that the FTO (fat mass and obesity-associated protein), an m6A demethylase, plays a critical role in cardiac contractile function during homeostasis, remodeling, and regeneration. Methods: We used clinical human samples, preclinical pig and mouse models, and primary cardiomyocyte cell cultures to study the functional role of m6A and FTO in the heart and in cardiomyocytes. We modulated expression of FTO by using adeno-associated virus serotype 9 (in vivo), adenovirus (both in vivo and in vitro), and small interfering RNAs (in vitro) to study its function in regulating cardiomyocyte m6A, calcium dynamics and contractility, and cardiac function postischemia. We performed methylated (m6A) RNA immunoprecipitation sequencing to map transcriptome-wide m6A, and methylated (m6A) RNA immunoprecipitation quantitative polymerase chain reaction assays to map and validate m6A in individual transcripts, in healthy and failing hearts, and in myocytes. Results: We discovered that FTO has decreased expression in failing mammalian hearts and hypoxic cardiomyocytes, thereby increasing m6A in RNA and decreasing cardiomyocyte contractile function. Improving expression of FTO in failing mouse hearts attenuated the ischemia-induced increase in m6A and decrease in cardiac contractile function. This is performed by the demethylation activity of FTO, which selectively demethylates cardiac contractile transcripts, thus preventing their degradation and improving their protein expression under ischemia. In addition, we demonstrate that FTO overexpression in mouse models of myocardial infarction decreased fibrosis and enhanced angiogenesis. Conclusions: Collectively, our study demonstrates the functional importance of the FTO-dependent cardiac m6A methylome in cardiac contraction during heart failure and provides a novel mechanistic insight into the therapeutic mechanisms of FTO.

Cytokines and Cardiac Contractile Function

Circulation ◽  
1997 ◽  
Vol 95 (4) ◽  
pp. 778-781 ◽  
Author(s):  
Ralph A. Kelly ◽  
Thomas W. Smith
Keyword(s):  
Contractile Function ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile

scholarly journals Regulation of Cardiac PKA Signaling by cAMP and Oxidants

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 663
Author(s):  
Friederike Cuello ◽  
Friedrich W. Herberg ◽  
Konstantina Stathopoulou ◽  
Philipp Henning ◽  
Simon Diering
Keyword(s):  
Contractile Function ◽  
Cardiac Contractility ◽  
Cellular Protein ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Main Driver ◽  
Dependent Protein ◽  
Relevant Regulation ◽  
Protein Dysfunction ◽  
Substrate Proteins

Pathologies, such as cancer, inflammatory and cardiac diseases are commonly associated with long-term increased production and release of reactive oxygen species referred to as oxidative stress. Thereby, protein oxidation conveys protein dysfunction and contributes to disease progression. Importantly, trials to scavenge oxidants by systemic antioxidant therapy failed. This observation supports the notion that oxidants are indispensable physiological signaling molecules that induce oxidative post-translational modifications in target proteins. In cardiac myocytes, the main driver of cardiac contractility is the activation of the β-adrenoceptor-signaling cascade leading to increased cellular cAMP production and activation of its main effector, the cAMP-dependent protein kinase (PKA). PKA-mediated phosphorylation of substrate proteins that are involved in excitation-contraction coupling are responsible for the observed positive inotropic and lusitropic effects. PKA-actions are counteracted by cellular protein phosphatases (PP) that dephosphorylate substrate proteins and thus allow the termination of PKA-signaling. Both, kinase and phosphatase are redox-sensitive and susceptible to oxidation on critical cysteine residues. Thereby, oxidation of the regulatory PKA and PP subunits is considered to regulate subcellular kinase and phosphatase localization, while intradisulfide formation of the catalytic subunits negatively impacts on catalytic activity with direct consequences on substrate (de)phosphorylation and cardiac contractile function. This review article attempts to incorporate the current perception of the functionally relevant regulation of cardiac contractility by classical cAMP-dependent signaling with the contribution of oxidant modification.

scholarly journals Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

2009 ◽  
Vol 297 (3) ◽  
pp. R682-R689 ◽  
Author(s):  
Yinan Hua ◽  
Heng Ma ◽  
Willis K. Samson ◽  
Jun Ren
Keyword(s):  
Contractile Function ◽  
Peptide Hormone ◽  
Left Ventricular ◽  
Maximal Velocity ◽  
Cardiac Contractile Function ◽  
Mechanical Responses ◽  
Cardiac Contractile ◽  
Short Term Exposure ◽  
The Impact ◽  
Dependent Mechanism

Neuronostatin, a newly identified peptide hormone sharing the same precursor with somatostatin, exerts multiple pharmacological effects in gastrointestinal tract, hypothalamus, and cerebellum. However, the cardiovascular effect of neuronostatin is unknown. The aim of this study was to elucidate the impact of neuronostatin on cardiac contractile function in murine hearts and isolated cardiomyocytes. Short-term exposure of neuronostatin depressed left ventricular developed pressure (LVDP), maximal velocity of pressure development (±dP/d t), and heart rate in Langendorff heart preparation. Consistently, neuronostatin inhibited peak shortening (PS) and maximal velocity of shortening/relengthening (±dL/d t) without affecting time-to-PS (TPS) and time-to-90% relengthening (TR90) in cardiomyocytes. The neuronostatin-elicited cardiomyocyte mechanical responses were mimicked by somatostatin, the other posttranslational product of preprosomatostatin. Furthermore, the neuronostatin-induced cardiomyocyte mechanical effects were ablated by the PKA inhibitor H89 (1 μM) and the Jun N-terminal kinase (JNK) inhibitor SP600125 (20 μM). The PKC inhibitor chelerythrine (1 μM) failed to alter neuronostatin-induced cardiomyocyte mechanical responses. To the contrary, chelerythrine, but not H89, abrogated somatostatin-induced cardiomyocyte contractile responses. Our results also showed enhanced c-fos and c-jun expression in response to neuronostatin exposure (0.5 to 2 h). Taken together, our data suggest that neuronostatin is a peptide hormone with overt cardiac depressant action. The neuronostatin-elicited cardiac contractile response appears to be mediated, at least in part, through a PKA- and/or JNK-dependent mechanism.

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