Susceptibility to ischemia-induced ventricular fibrillation in isolated female rat hearts varies moderately with estrous cycle stage

Annexin 1 (ANXA1) is a Ca2+- and phospholipid-binding protein that plays an important role as a mediator of glucocorticoid action in the host-defence and neuroendocrine systems. Sex differences in hypothalamo–pituitary–adrenal (HPA) axis activity are well documented and a number of studies have demonstrated that gonadal steroids act as regulators of HPA activity. The aim of this study was to investigate the effect of ovariectomyand 17β-estradiol replacement, and estrous cycle stage, on anterior pituitary ANXA1 content. The amount of anterior pituitary ANXA1 determined by western blotting varied with estrous cycle stage with a peak at estrus declining to a trough at proestrus. Ovariectomy resulted in a significant (P<0.05) decrease in anterior pituitary ANXA1 content. Administration of 17β-estradiol (1 μg/100 g) significantly (P<0.01) increased anterior pituitary ANXA1 expression in the ovariectomized animals. In contrast, there was no change in pituitary ANXA1 content in response to 17β-estradiol in adrenalectomized and adrenalectomized/ovariectomized rats. Treatment of TtT/GF cells, a folliculo-stellate cell line, with 17β-estradiol (1.8–180 nM) increased ANXA1 mRNA expression and increased the amount of ANXA1 protein externalized in response to a dexamethasone stimulus. These results indicate that 17β-estradiol stimulates ANXA1 expression in the anterior pituitary and in vivo an adrenal factor contributes to the mechanism of action.

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Expression patterns of Arc mRNA after renewal of appetitive behavior in female rats.

10.1101/2021.07.20.453088 ◽

2021 ◽

Author(s):

Emily N Hilz ◽

Laura A Agee ◽

Donyun S Jun ◽

Marie H Monfils ◽

Hongjoo J Lee

Keyword(s):

Estrous Cycle ◽

Expression Patterns ◽

Neuronal Population ◽

Extinction Training ◽

Female Rats ◽

Early Gene ◽

Female Rat ◽

Appetitive Behavior ◽

Neuronal Populations ◽

Estrous Cycle Stage

Renewal of appetitive behavior depends on the gonadal hormonal state of the female rat. In this experiment the effect of female rat estrous cycle stage on renewal of appetitive behaviors is replicated and extended upon to understand how endogenous hormonal states around the estrous cycle drive renewal at the neuronal population level. Estrous cycle stage (i.e., proestrus (P, high hormone) or metestrus/diestrus (M/D, low hormone)) was considered during two important learning and behavioral expression windows: at extinction training and during LTM/renewal testing. First, rats in P during context-dependent extinction training but in some other stage of the estrous cycle during long-term memory and renewal testing (Different) were shown to exhibit more renewal of conditioned foodcup (but not conditioned orienting) behavior compared to rats in other estrous cycle groups. Next, cellular compartment analysis of temporal activity using fluorescence in situ hybridization (catFISH) was used to examine immediate early gene activity of Arc mRNA in neuronal populations after distinct context-stimulus exposures (i.e., extinction and acquisition test contexts). Arc mRNA expression patterns were examined in the prefrontal cortex (PFC), amygdala, hippocampus (HPC), and paraventricular nucleus of the thalamus. P-different rats showed differential neuronal population activity in the infralimbic cortex of the PFC, the lateral amygdaloid nucleus, and both CA1 and CA3 regions of the dorsal HPC. In each region P-different rats exhibited more co-expression and less specificity of Arc mRNA compared to other hormonal groups, indicating that renewal of appetitive foodcup behavior induces Arc mRNA in overlapping neuronal populations in female rats.

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Glycolytic inhibition causes spontaneous ventricular fibrillation in aged hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00128.2011 ◽

2011 ◽

Vol 301 (1) ◽

pp. H180-H191 ◽

Cited By ~ 32

Author(s):

Norishige Morita ◽

Jong-Hwan Lee ◽

Aneesh Bapat ◽

Michael C. Fishbein ◽

William J. Mandel ◽

...

Keyword(s):

Ventricular Fibrillation ◽

Connexin 43 ◽

Left Ventricular ◽

Triggered Activity ◽

Adult Rat ◽

Rat Hearts ◽

Intracellular Calcium Ion ◽

Dependent Protein ◽

Isolated Cardiac Myocytes ◽

Delayed Afterdepolarizations

Selective glycolytic inhibition (GI) promotes electromechanical alternans and triggered beats in isolated cardiac myocytes. We sought to determine whether GI promotes triggered activity by early afterdepolarization (EAD) or delayed afterdepolarizations in intact hearts isolated from adult and aged rats. Dual voltage and intracellular calcium ion (Cai2+) fluorescent optical maps and single cell glass microelectrode recordings were made from the left ventricular (LV) epicardium of isolated Langendorff-perfused adult (∼4 mo) and aged (∼24 mo) rat hearts. GI was induced by replacing glucose with 10 mM pyruvate in oxygenated Tyrode's. Within 20 min, GI slowed Cai2+ transient decline rate and shortened action potential duration in both groups. These changes were associated with ventricular fibrillation (VF) in the aged hearts (64 out of 66) but not in adult hearts (0 out of 18; P < 0.001). VF was preceded by a transient period of focal ventricular tachycardia caused by EAD-mediated triggered activity leading to VF within seconds. The VF was suppressed by the ATP-sensitive K (KATP) channel blocker glibenclamide (1 μM) but not (0 out of 7) by mitochondrial KATP block. The Ca-calmodulin-dependent protein kinase II (CaMKII) blocker KN-93 (1 μM) prevented GI-mediated VF ( P < 0.05). Block of Na-Ca exchanger (NCX) by SEA0400 (2 μM) prevented GI-mediated VF (3 out of 6), provided significant bradycardia did not occur. Aged hearts had significantly greater LV fibrosis and reduced connexin 43 than adult hearts ( P < 0.05). We conclude that in aged fibrotic unlike in adult rat hearts, GI promotes EADs, triggered activity, and VF by activation of KATP channels CaMKII and NCX.

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Sex Hormones Regulate Rat Hepatic Monocarboxylate Transporter Expression and Membrane Trafficking

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3ch29 ◽

2017 ◽

Vol 20 (1) ◽

pp. 435 ◽

Cited By ~ 2

Author(s):

Jieyun Cao ◽

Michael Ng ◽

Melanie A Felmlee

Keyword(s):

Sex Differences ◽

Membrane Protein ◽

Protein Expression ◽

Estrous Cycle ◽

Sex Hormones ◽

Membrane Trafficking ◽

Drug Disposition ◽

Membrane Expression ◽

Membrane Protein Expression ◽

Estrous Cycle Stage

Purpose: Monocarboxylate transporters (MCTs) are involved in the transport of monocarboxylates such as ketone bodies, lactate, and pharmaceutical agents. CD147 functions as an ancillary protein for MCT1 and MCT4 for plasma membrane trafficking. Sex differences in MCT1 and MCT4 have been observed in muscle and reproductive tissues; however, there is a paucity of information on MCT sex differences in tissues involved in drug disposition. The objective of the present study was to quantify hepatic MCT1, MCT4 and CD147 mRNA, total cellular and membrane protein expression in males, over the estrous cycle in females and in ovariectomized (OVX) females. Method: Liver samples were collected from females at the four estrous cycle stages (proestrus, estrus, metestrus, diestrus), OVX females and male Sprague-Dawley rats (N = 3 – 5). Estrus cycle stage of females was determined by vaginal lavage. mRNA and protein (total and membrane) expression of MCT1, MCT4 and CD147 was evaluated by qPCR and western blot analysis. Results: MCT1 mRNA and membrane protein expression varied with estrous cycle stage, with OVX females having higher expression than males, indicating that female sex hormones may play a role in MCT1 regulation. MCT4 membrane expression varied with estrous cycle stage with expression significantly lower than males. MCT4 membrane expression in OVX females was also lower than males, suggesting that androgens play a role in membrane expression of MCT4. Males had higher membrane CD147 expression, whereas there was no difference in whole cell protein and mRNA levels suggesting that androgens are involved in regulating CD147 membrane localization. Conclusions: This study demonstrates hepatic expression and membrane localization of MCT1, MCT4 and CD147 are regulated by sex hormones. Sex differences in hepatic MCT expression may lead to altered drug disposition, so it is critical to elucidate the underlying mechanisms in the sex hormone-dependent regulation of MCT expression. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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SKA-31, a novel activator of SKCa and IKCa channels, increases coronary flow in male and female rat hearts

Cardiovascular Research ◽

10.1093/cvr/cvs326 ◽

2012 ◽

Vol 97 (2) ◽

pp. 339-348 ◽

Cited By ~ 26

Author(s):

Ramesh C. Mishra ◽

Darrell Belke ◽

Heike Wulff ◽

Andrew P. Braun

Keyword(s):

Coronary Flow ◽

Female Rat ◽

Male And Female ◽

Rat Hearts

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Influence of the estrous cycle on hypoxic failure in the female rat heart

Gender Medicine ◽

10.1016/j.genm.2009.12.005 ◽

2009 ◽

Vol 6 (4) ◽

pp. 596-603 ◽

Cited By ~ 2

Author(s):

Tom L. Broderick ◽

Peter Wong

Keyword(s):

Estrous Cycle ◽

Rat Heart ◽

Female Rat

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Abstract 15555: Administration of c-Kit+ Cardiac Stem Cells (CSCs) Results in Increased Proliferation and Cardiac Content of CSCs 1 Year Later

Circulation ◽

10.1161/circ.130.suppl_2.15555 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Qianhong Li ◽

Ning Chen ◽

Li Luo ◽

Qinghui Ou ◽

Wei Xie ◽

...

Keyword(s):

Stem Cells ◽

Border Zone ◽

Functional Improvement ◽

Vehicle Group ◽

Lv Function ◽

Female Rat ◽

Infarct Zone ◽

Hematopoietic Stem ◽

Beneficial Effects ◽

Rat Hearts

Background: We have previously shown in rats that the beneficial effects of c-kit + CSCs on LV function and remodeling post-myocardial infarction persist for at least 1 year after CSC administration. However, in that study the retention of transplanted Y-chromosome + cells in the risk region (RR) of female rat hearts at 1 year was low (<10% of total nuclei) and not sufficient to account for the functional improvement, suggesting that other mechanisms must be at work. Methods and Results: To address this issue, rats received intracoronary vehicle or 1x10 6 syngeneic CSCs 4 h after a 90-min coronary occlusion; 11 months later, BrdU treatment was given for 1 month. CSCs, which are c-kit + /CD45 − , were distinguished from c-kit + hematopoietic stem cells/mast cells, which are CD45 + . At 1 year after CSC administration, the total number of c-kit + or c-kit + /BrdU + cells in the heart (the sum of c-kit + /CD45 − and c-kit + /CD45 + cells) did not differ between CSC and control groups (Figs. H and I). However, CSC transplantation resulted in increased numbers of CSCs (c-kit + /CD45 − cells) in the RR (i.e., the infarct zone plus border zone)(47.6±7.0% of total c-kit + cells vs. 27.9±4.1% in vehicle group; n=5, P <0.05; Fig. J). Among CSCs (c-kit + /CD45 − cells), the fraction that was newly formed (c-kit + /CD45 − /BrdU + ) was dramatically increased in the RR of the CSC group (+ 2.6-fold vs. vehicle group; n=4, P <0.05; Fig. M), indicating increased CSC proliferation and turnover. Conclusions: These data reveal, for the first time, that a single intracoronary infusion of CSCs is followed by an increase in both the proliferation and the total number of c-kit + CSCs in the myocardium that persists, surprisingly, for at least 1 year after cell delivery. Since transplanted cells do not differentiate into adult myocytes, these data suggest that the long-term salubrious effects of CSCs on cardiac function are mediated by sustained activation of the CSC pool in the heart.

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Electrically-Induced Ventricular Fibrillation Alters Cardiovascular Function and Expression of Apoptotic and Autophagic Proteins in Rat Hearts

International Journal of Molecular Sciences ◽

10.3390/ijms20071628 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1628 ◽

Cited By ~ 4

Author(s):

Andras Czegledi ◽

Agnes Tosaki ◽

Alexandra Gyongyosi ◽

Rita Zilinyi ◽

Arpad Tosaki ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Ventricular Fibrillation ◽

Cardiac Death ◽

Caspase 3 ◽

Recovery Period ◽

Heart Rhythm ◽

Heart Tissue ◽

Altered Expression ◽

Cardiac Functions ◽

Rat Hearts

Background: The pathological heart contractions, called arrhythmias, especially ventricular fibrillation (VF), are a prominent feature of many cardiovascular diseases leading to sudden cardiac death. The present investigation evaluates the effect of electrically stimulated VF on cardiac functions related to autophagy and apoptotic mechanisms in isolated working rat hearts. Methods: Each group of hearts was subjected to 0 (Control), 1, 3, or 10 min of spacing-induced VF, followed by 120 min of recovery period and evaluated for cardiac functions, including aortic flow (AF), coronary flow (CF), cardiac output (CO), stroke volume (SV), and heart rate (HR). Hearts were also evaluated for VF effects on infarcted zone magnitude and Western blot analysis was conducted on heart tissue for expression of the apoptotic biomarker cleaved-caspase-3 and the autophagy proteins: p62, P-mTOR/mTOR, LC3BII/LC3BI ratio, and Atg5-12 complexes. Results: Data revealed that VF induced degradation in AF, CF, CO, and SV, which prominently included-variable post-VF capacity for recovery of normal heart rhythm; increased extent of infarcted heart tissue; altered expression of cleaved-caspase-3 suggesting potential for VF-mediated amplification of apoptosis. VF influence on expression of p62, LC3BII/LC3BI, and Atg5-12 proteins was complex, possibly due to differential effects of VF-induced expression on proteins comprising the autophagic program. Conclusions: VF was observed to cause time-dependent changes in autophagy processes, which with additional analysis under ongoing investigations, likely to yield novel therapeutic targets for the prevention of VF and sudden cardiac death.

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Nature of [Ca2+]i transients during ventricular fibrillation and quinidine treatment in perfused rat hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.266.4.h1473 ◽

1994 ◽

Vol 266 (4) ◽

pp. H1473-H1484

Author(s):

S. Kojima ◽

J. Wikman-Coffelt ◽

S. T. Wu ◽

W. W. Parmley

Keyword(s):

Ventricular Fibrillation ◽

Control Level ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Acetoxymethyl Ester ◽

Ecg Signals ◽

Rat Hearts ◽

Perfused Rat Hearts ◽

Electrocardiogram Ecg ◽

The Relationship

We studied intracellular Ca2+ concentration ([Ca2+]i) and the electrocardiographic signals during pacing-induced ventricular fibrillation (VF) and quinidine treatment (0.4 mg/min) using surface fluorometry in indo 1-acetoxymethyl ester (AM)-loaded perfused rat hearts. [Ca2+]i was evaluated as the indo 1 fluorescence ratio (F400/F510) and expressed as a percentage of the control amplitude of F400/F510 transients. F400/F510 increased to approximately 250% during 2- (n = 14) or 20-min (n = 9) VF. Quinidine significantly decreased F400/F510 by 60% after 2-min VF; however, this effect was blunted after 20-min VF. After 2-min VF, F400/F510 and left ventricular pressure recovered almost to the control level. However, recovery of F400/F510 and ventricular function was poor after 20-min VF. The relationship between [Ca2+]i and the electrocardiogram (ECG) during VF was evaluated by power spectrum analysis of F400/F510 and ECG signals. During VF (25 +/- 3 Hz) with high irregularity, there were no clear [Ca2+]i transients (n = 110). When the cardiac rhythm (22 +/- 3 Hz) was regular, including ventricular tachycardia, there were recognizable [Ca2+]i signals with dominant frequencies that were the same (n = 2), one-half (n = 12), or one-third (n = 1) of the ECG frequencies. The highest frequency of the [Ca2+]i transients was 19 Hz. During quinidine treatment, the VF rate decreased significantly, and clear [Ca2+]i transients were noted in all records responding to every one or two ECG signals. The conclusions were the following: 1) [Ca2+]i responds to electrical signals rapidly (up to 19 Hz) during VF. This fast [Ca2+]i response is a probable cause of high [Ca2+]i during VF. 2) Quinidine decreased [Ca2+]i after 2-min VF possibly in part by slowing the VF and [Ca2+]i transients rates. 3) 20-min VF caused [Ca2+]i overload and poor functional recovery after defibrillation.

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