scholarly journals Testosterone modulates cardiomyocyte Ca2+ handling and contractile function

2009 ◽  
pp. 293-297 ◽  
Author(s):  
CL Curl ◽  
LMD Delbridge ◽  
BJ Canny ◽  
IR Wendt
Keyword(s):  
Sex Differences ◽  
Cardiac Function ◽  
Time Course ◽  
Direct Evidence ◽  
Contractile Function ◽  
Testosterone Replacement

The extent to which sex differences in cardiac function may be attributed to the direct myocardial influence of testosterone is unclear. In this study the effects of gonadal testosterone withdrawal (GDX) and replacement (GDX+T) in rats, on cardiomyocyte shortening and intracellular Ca2+ handling was investigated (0.5 Hz, 25 o C). At all extracellular [Ca2+] tested (0.5-2.0 mM), the Ca2+ transient amplitude was significantly reduced (by ~ 50 %) in myocytes of GDX rats two weeks postgonadectomy. The time course of Ca2+ transient decay was significantly prolonged in GDX myocytes (tau, 455±80 ms) compared with intact (279±23 ms) and GDX+T (277±19 ms). Maximum shortening of GDX myocytes was markedly reduced (by more than 60 %) and relaxation significantly delayed (by more than 35 %) compared with intact and GDX+T groups. Thus testosterone replacement completely reversed the cardiomyocyte hypocontractility induced by gonadectomy. These results provide direct evidence for a role of testosterone in regulating functional Ca2+ handling and contractility in the heart.

Time course of regression of the protection conferred by simulated high altitude to rat myocardium: correlation with mtNOS

2008 ◽  
Vol 105 (3) ◽  
pp. 951-957 ◽  
Author(s):  
Pablo La Padula ◽  
Juanita Bustamante ◽  
Analía Czerniczyniec ◽  
Lidia E. Costa
Keyword(s):  
Left Ventricle ◽  
Time Course ◽  
Contractile Function ◽  
Mechanical Activity ◽  
Simulated High Altitude ◽  
Mitochondrial Nitric Oxide Synthase ◽  
Contraction And Relaxation ◽  
Oxide Synthase ◽  
Linear Decline

During acclimatization to sustained hypobaric hypoxia, retardation of age-associated decline in left ventricle mechanical activity and improved posthypoxic recovery were accompanied by upregulation of mitochondrial nitric oxide synthase (mtNOS). To evaluate the time course of regression of these effects on deacclimatization, rats exposed to 53.8 kPa in a hypopressure chamber for 5 mo were returned to 101.3 kPa, whereas controls remained at 101.3 kPa throughout the study. At three time points, contractile function in response to calcium and to hypoxia-reoxygenation (H/R) were determined in papillary muscle, and NOS activity and expression were determined in mitochondria isolated from left ventricle. Developed tension was, before H/R, 65, 58, and 40%, and, after H/R, 129, 107, and 71% higher than in controls at 0.4, 2, and 5 mo of normoxia, respectively. Maximal rates of contraction and relaxation followed a similar pattern. All three parameters showed a linear decline during deacclimatization, with mean half-time ( t1/2) of 5.9 mo for basal mechanical activity and 5.3 mo for posthypoxic recovery. Left ventricle mtNOS activity was 42, 27, and 20% higher than in controls at 0.4, 2, and 5 mo, respectively ( t1/2 = 5.0 mo). The expression of mtNOS showed similar behavior. The correlation of mtNOS activity with muscle contractility sustained a biphasic modulation, suggesting an optimal mtNOS activity. This experimental model would provide the most persistent effect known at present on preservation of myocardial mechanical activity and improved tolerance to O2 deprivation. Results support the putative role of mtNOS in the mechanism involved.

Alterations in sarcoplasmic reticulum function and gene expression in ischemic-reperfused rat heart

1999 ◽  
Vol 277 (2) ◽  
pp. H584-H594 ◽  
Author(s):  
Rana M. Temsah ◽  
Thomas Netticadan ◽  
Donald Chapman ◽  
Satoshi Takeda ◽  
Seibu Mochizuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Function ◽  
Contractile Function ◽  
Critical Role ◽  
Cardiac Contraction ◽  
Mrna Levels ◽  
Rat Hearts ◽  
The Status ◽  
Sr Gene

In view of the critical role of sarcoplasmic reticular (SR) Ca2+ release and the Ca2+ pump in cardiac contraction-relaxation, this study was undertaken to assess the status of SR function, protein content, and gene expression in isolated rat hearts subjected to global ischemia for 30 min followed by 60 min of reperfusion (I/R). Attenuated recovery of contractile function in the I/R hearts was associated with reduced SR Ca2+ uptake, Ca2+ release, and ryanodine-binding activities. mRNA levels and protein contents for SR Ca2+ pump ATPase and Ca2+ release channels were markedly depressed in the I/R hearts. Perfusion of hearts with superoxide dismutase plus catalase, well-known scavengers of oxyradicals, prevented the I/R-induced alterations in cardiac function and partially prevented SR Ca2+transport activities and mRNA abundance. In hearts perfused with xanthine plus xanthine oxidase or H2O2, changes similar to those in the I/R hearts were observed. These results indicate that oxyradicals may participate in depressing the SR Ca2+ handling and gene expression in the I/R heart. It is suggested that treatment of hearts with antioxidants may improve the recovery of cardiac function by preserving the SR function and partially protecting the SR gene expression.

Abstract 381: Mcur1 is a Potential Target to Modulate Cardiac Contractility and Alleviate Cardiac Function During Heart Failure

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Rajika Roy ◽  
Santhanam Shanmughapriya ◽  
Xueqian Zhang ◽  
Jianliang Song ◽  
Dhanendra Tomar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Contractile Function ◽  
Cardiac Contractility ◽  
Pressure Overload ◽  
Dominant Negative ◽  
Selective Channel

Cardiac contractility is regulated by the intracellular Ca 2+ concentration fluxes which are actively regulated by multiple channels and transporters. Ca 2+ uptake into the mitochondrial matrix is precisely controlled by the highly Ca 2+ selective channel, Mitochondrial Calcium Uniporter (MCU). Earlier studies on the cardiac-specific acute MCU knockout and a transgenic dominant-negative MCU mice have demonstrated that mitochondrial Ca 2+ ( m Ca 2+ ) signaling is necessary for cardiac ‘‘fight-or-flight’’ contractile response, however, the role of m Ca 2+ buffering to shape global cytosolic Ca 2+ levels and affect E-C coupling, particularly the Ca 2+ transient, on a beat-to-beat basis still remains to be solved. Our earlier studies have demonstrated that loss of MCU Regulator 1 (MCUR1) in cardiomyocytes results in the impaired m Ca 2+ uptake. We have now employed the cardiac-specific MCUR1 knockout mouse to dissect the precise role of MCU in regulating cytosolic Ca 2+ transients associated with excitation-contraction (E-C) coupling and cardiac function. Results from our studies including the in vivo analyses of cardiac physiology during normal and pressure-overloaded mouse models and in vitro experiments including single-cell cardiac contractility, calcium transients, and electrophysiology measurements demonstrate that MCUR1/MCU regulated m Ca 2+ buffering in cardiomyocytes, although insignificant under basal condition, becomes critical in stress induced conditions and actively participates in regulating the c Ca 2+ transients. Also, the ablation of MCUR1 in cardiomyocytes during stress conditions prevents m Ca 2+ overload and subsequent mROS overproduction. Our data indicate that MCUR1 ablation offers protection against pressure-overload cardiac hypertrophy. In summary, our results provide critical insights into the mechanisms by which the MCU channel contributes in regulating the contractile function of the cardiomyocytes and the role of m Ca 2+ in the development and progression of heart failure.

Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload

2016 ◽  
Vol 131 (2) ◽  
pp. 141-154 ◽  
Author(s):  
Wei-ming Li ◽  
Yi-fan Zhao ◽  
Guo-fu Zhu ◽  
Wen-hui Peng ◽  
Meng-yun Zhu ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Contractile Function ◽  
Pressure Overload ◽  
Loss Of Function ◽  
Pathological Cardiac Hypertrophy ◽  
Dual Specific Phosphatase

Pathological cardiac hypertrophy is an independent risk factor of heart failure. However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12 is a member of the dual specific phosphatase (DUSP) family, which is characterized by its DUSP activity to dephosphorylate both tyrosine and serine/threonine residues on one substrate. Some DUSPs have been identified as being involved in the regulation of cardiac hypertrophy. However, the role of DUSP12 during pathological cardiac hypertrophy is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in hypertrophic hearts and cardiomyocytes. Using a genetic loss-of-function murine model, we demonstrated that DUSP12 deficiency apparently aggravated pressure overload-induced cardiac hypertrophy and fibrosis as well as impaired cardiac function, whereas cardiac-specific overexpression of DUPS12 was capable of reversing this hypertrophic and fibrotic phenotype and improving contractile function. Furthermore, we demonstrated that JNK1/2 activity but neither ERK1/2 nor p38 activity was increased in the DUSP12 deficient group and decreased in the DUSP12 overexpression group both in vitro and in vivo under hypertrophic stress conditions. Pharmacological inhibition of JNK1/2 activity (SP600125) is capable of reversing the hypertrophic phenotype in DUSP12 knockout (KO) mice. DUSP12 protects against pathological cardiac hypertrophy and related pathologies. This regulatory role of DUSP12 is primarily through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 could be a promising therapeutic target of pathological cardiac hypertrophy. DUSP12 is down-regulated in hypertrophic hearts. An absence of DUSP12 aggravated cardiac hypertrophy, whereas cardiomyocyte-specific DUSP12 overexpression can alleviate this hypertrophic phenotype with improved cardiac function. Further study demonstrated that DUSP12 inhibited JNK activity to attenuate pathological cardiac hypertrophy.

Abstract 753: Effects of Na,K-ATPase Beta-Subunit Knockout on Heart Function

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sonali P Barwe ◽  
Maria C Jordan ◽  
Anna Skay ◽  
Landon Inge ◽  
Sigrid A Rajasekaran ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Knockout Mice ◽  
Contractile Function ◽  
Heart Function ◽  
Cardiac Contractility ◽  
Beta Subunit ◽  
Alpha Subunit ◽  
Subunit Gene ◽  
Beta Subunit Gene

Na,K-ATPase also known as the sodium pump, is an oligomeric membrane bound enzyme that catalyzes ATP-dependent transport of three Na + ions out and two K + ions into the cell. It plays an important role in cardiac function by influencing the intracellular Ca 2+ levels via the Na + /Ca 2+ exchanger and thereby cardiac contractility. Na,K-ATPase is composed of two essential subunits, alpha-subunit and beta-subunit, both of which have multiple isoforms. The alpha subunit, which is also the catalytic subunit, is the receptor for cardiac glycosides such as digitalis, used for the treatment of congestive heart failure. Evidence indicates that Na,K-ATPase alpha1, alpha2 and beta1 isoforms as well as the Na,K-ATPase enzymatic activity is reduced in the failing human heart. Heterozygous knockout mice of the alpha-subunit isoforms had altered cardiac contractility. However, nothing much is known about the role of the beta-subunit in cardiac function. To investigate the role of beta-subunit in the myocardium, we used Cre/loxP technology to inactivate the beta-subunit gene exclusively in ventricular cardiac myocytes. Animals with homozygous ventricular myocyte beta-subunit gene excision were born at the expected Mendelian ratio, grew into adulthood, and appeared to be healthy until 9 months of age. These animals had ~20% and ~50% of control levels of beta-subunit and alpha-subunit protein in the heart respectively. At 13–14 months of age, these mice had 24% higher heart/body weight ratios, elevated levels of markers of cardiac hypertrophy such as ANP, BNP, alpha MHC, alpha skeletal actin, and reduced contractility by echocardiography (56.7% versus 66.4% EF in the WT, n = 7 each) as compared to their WT littermates. Pressure overload by transverse aortic constriction in younger mice, resulted in compensated hypertrophy in WT mice, but 50% of Na,K-beta knockout mice died soon after TAC. The few survivors exhibited decreased contractile function (50% as compared to 71% EF in WT, n = 4 each) and mimicked the effects of Na,K-beta knockout in old mice. In conclusion, our results suggest that loss of beta-subunit leads to significant pathophysiology from altered ionic homeostasis in the heart.

Direct Evidence for the Role of Inhibition in Resolving Interference

2009 ◽  
Author(s):  
M. Karl Healey ◽  
Karen L. Campbell ◽  
Lynn Hasher ◽  
Lynn Ossher
Keyword(s):  
Direct Evidence

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Time Course ◽  
Essential Role ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
High Doses ◽  
Induced Aggregation

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

Intersexual and Intrasexual Competition and Their Relation to Jealousy

2019 ◽  
pp. 214-236
Author(s):  
Abraham P. Buunk ◽  
Karlijn Massar ◽  
Pieternel Dijkstra ◽  
Ana María Fernández
Keyword(s):  
Sex Differences ◽  
Individual Differences ◽  
Menstrual Cycle ◽  
Attachment Styles ◽  
Mate Guarding ◽  
Intrasexual Competition ◽  
Online Infidelity ◽  
Intersexual Competition

This chapter discusses sex differences in intersexual competition and describes particularly the consequences of such competition for conflict between the sexes, as well as for sex differences in mate guarding and, relatedly, in the types of infidelity that evoke jealousy, including online infidelity. It also discusses individual differences in jealousy as related to attachment styles and describes the effects of height, hormones, and the menstrual cycle on jealousy. Next, the chapter moves on to intrasexual competition and discusses, among other topics, intrasexual competition among men and among women, the role of sex differences in rival characteristics in evoking jealousy, the role of attachment styles and hormones, and individual differences in intrasexual competitiveness.

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