scholarly journals Pressure-volume analysis reveals characteristic sex-related differences in cardiac function in a rat model of aortic banding-induced myocardial hypertrophy

2018 ◽  
Vol 315 (3) ◽  
pp. H502-H511 ◽  
Author(s):  
Mihály Ruppert ◽  
Sevil Korkmaz-Icöz ◽  
Sivakkanan Loganathan ◽  
Weipeng Jiang ◽  
Lorenz Lehmann ◽  
...  
Keyword(s):  
Sex Differences ◽  
Myocardial Hypertrophy ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Female Rats ◽  
Lv Function ◽  
Active Relaxation ◽  
Male And Female ◽  
Volume Analysis ◽  
Male And Female Rats

Sex differences in pressure overload (PO)-induced left ventricular (LV) myocardial hypertrophy (LVH) have been intensely investigated. Nevertheless, sex-related disparities of LV hemodynamics in LVH were not examined in detail. Therefore, we aimed to provide a detailed characterization of distinct aspects of LV function in male and female rats during different stages of LVH. Banding of the abdominal aorta (AB) was performed to induce PO for 6 or 12 wk in male and female rats. Control animals underwent sham operation. The development of LVH was followed by serial echocardiography. Cardiac function was assessed by pressure-volume analysis. Cardiomyocyte hypertrophy and fibrosis were evaluated by histology. At week 6, increased LV mass index, heart weight-to-tibial length, cardiomyocyte diameter, concentric LV geometry, and moderate interstitial fibrosis were detected in both male and female AB rats, indicating the development of an early stage of LVH. Functionally, at this time, impaired active relaxation, increased contractility, and preserved ventricular-arterial coupling were observed in the AB groups in both sexes. In contrast, at week 12, progressive deterioration of LVH-associated structural and functional alterations occurred in male but not female animals with sustained PO. Accordingly, at this later stage, LVH was associated with eccentric remodeling, exacerbated fibrosis, and increased chamber stiffness in male AB rats. Furthermore, augmented contractility declined in male but not female AB animals, resulting in contractility-afterload mismatch. Maintained contractility augmentation, preserved ventricular-arterial coupling, and better myocardial compliance in female rats contribute to sex differences in LV function during the progression of PO-induced LVH. NEW & NOTEWORTHY We investigated sex differences in pressure overload-induced left ventricular myocardial hypertrophy for the first time on the functional level by pressure-volume analysis. We found that left ventricular hypertrophy was initially characterized by prolonged active relaxation, increased contractility, and maintained ventricular-arterial coupling in both sexes. However, at a later stage, augmented contractility declined in mate but not female rats, resulting in contractility-afterload mismatch. Furthermore, in male rats, increased myocardial stiffness also contributed to hypertrophy-associated diastolic dysfunction.

scholarly journals Sex-related differences in cardiac and myofilament function in rats with pressure-overload induced left ventricular hypertrophy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Radovits ◽  
M Ruppert ◽  
A Olah ◽  
A.A Sayour ◽  
B.A Barta ◽  
...  
Keyword(s):  
Late Stage ◽  
Myocardial Hypertrophy ◽  
Systolic Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Female Rats ◽  
Funding Source ◽  
Male And Female ◽  
Myofilament Function ◽  
Lv Systolic Function

Abstract Introduction Recent findings indicate that sex is a major determinant of left ventricular (LV) structure in pressure overload (PO)-induced LV myocardial hypertrophy (LVH). However, data are scare regarding sex-related differences in LV function in case of PO-evoked LVH. Aim Hence, in the present study we aimed at comprehensively investigating sex-related functional differences on the global cardiac level and also on the myofilament level in PO-induced LVH. Method Abdominal aortic banding (AB) was carried out to induce chronic PO for 6 or 12 weeks in male and female rats. Age- and sex-matched sham-operated animals served as controls. The development of LVH was followed by serial echocardiography. The extent of cardiomyocyte hypertrophy and myocardial fibrosis were evaluated by histology. Cardiac function was assessed by pressure-volume analysis. Force measurement was carried out in permeabilized cardiomyocytes to compute myofilament function. Results At week 6, robust myocardial hypertrophy, concentric LV geometry and moderate interstitial fibrosis were detected in both male and female AB rats. This early stage of PO-induced LVH was associated with increased LV contractility (slope of end-systolic pressure-volume relationship [ESPVR, mmHg/μl]: 3.09±0.18 Male-AB-wk6 vs. 1.79±0.22 Male-Sham-wk6 P<0.05; 3.68±0.77 Female-AB-wk6 vs. 1.87±0.21 Female-Sham-wk6 P<0.05) and enhanced myofilament Ca2+ sensitivity in both sexes (pCa50: 5.86±0.01 Male-AB-wk6 vs. 5.73±0.02 Male-Sham-wk6 P<0.05; 5.94±0.03 Female-AB-wk6 vs. 5.73±0.01 Female-Sham-wk6 P<0.05). At week 6, the augmented LV contractility effectively counterbalanced the increased afterload in both male and female AB groups. Hence, ventricular-arterial coupling (VAC) was maintained and LV systolic function was preserved in the AB groups in both sexes. In contrast, at week 12, marked sex differences could be observed. At this later stage, LVH was characterized by eccentric remodeling and intensified collagen accumulation in male AB rats. The initial LV contractility augmentation (slope of ESPVR, mmHg/μl: 1.74±0.13 Male-AB-wk12 vs. 1.31±0.17 Male-Sham-wk12 n.s.) as well as the enhanced myofilament Ca2+ sensitivity (pCa50: 5.78±0.02 Male-AB-wk12 vs. 5.75±0.01 Male-Sham-wk12 n.s.) diminished, leading to impaired VAC and reduced LV systolic function. On the contrary, in female AB rats, cardiac contractility (ESPVR, mmHg/ μl: 3.97±0.50 Female-AB-wk12 vs. 2.08±0.17 Female-Sham-wk12 P<0.05) and myofilament Ca2+ sensitivity (pCa50:5.85±0.02 Female-AB-wk12 vs. 5.78±0.01 Female-Sham-wk12 P<0.05) remained increased, resulting in adequate VAC and preserved LV systolic function at late-stage of PO-induced LVH as well. Conclusion The initially augmented LV contractility and enhanced myofilament Ca2+ sensitivity declines in male but not in female AB rats at later time points. Hence, characteristically different alterations occur in LV systolic function between the two sexes in late-stage of PO-evoked LVH. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NVKP_16-1-2016-0017.

Effects of sex differences on constitutive nitric oxide synthase expression and activity in response to pressure overload in rats

2007 ◽  
Vol 293 (5) ◽  
pp. H2650-H2658 ◽  
Author(s):  
Xavier Loyer ◽  
Patricia Oliviero ◽  
Thibaud Damy ◽  
Estelle Robidel ◽  
Françoise Marotte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sex Differences ◽  
Nitric Oxide Synthase ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase

Clinical studies have documented sex differences in left ventricular (LV) hypertrophy patterns, but the mechanisms are so far poorly defined. This study aimed to determine whether 1) severe pressure overload altered expression and/or activity of cardiac constitutive nitric oxide synthase (NOS1 and NOS3) and 2) these changes were modulated according to sex. Analyses were performed 0.4–20 wk after thoracic aortic constriction (TAC) in male and female Wistar rats. Male rats with TAC exhibited early signs of cardiac dysfunction, as shown by echocardiographic and LV end-diastolic pressure measurements, whereas females with TAC exhibited higher LV hypertrophy (+96% vs. males at 20 wk; P < 0.05). After TAC, cardiac NOS1 expression was rapidly induced (0.4 wk) and stable afterward in males ( P < 0.05 vs. sham groups), whereas it was delayed in females. Accordingly, specific NOS1 activity was increased by 2 wk in male rats with TAC (+122%; P < 0.001 vs. sham groups) and only by 20 wk in females (+220%; P < 0.001 vs. sham groups). NOS1 activity was correlated with NOS1 level. Regarding cardiac NOS3, expression was unaffected by TAC, and the decrease in activity observed at early and late times in male and female rats with TAC, respectively, is shown to be related to NOS3 allosteric regulator caveolin-1 level. The data demonstrated a unique sex-dependent regulation of the constitutive NOSs in response to TAC in rats; such a difference might play a role in the sex-dependent adaptability of the heart in response to pressure overload.

scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

scholarly journals Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  
Keyword(s):  
Sex Differences ◽  
Microbial Activity ◽  
Hepatic Steatosis ◽  
Female Rats ◽  
Male Rats ◽  
Calorie Intake ◽  
Dietary Copper ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rrna Sequencing

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

P3512Sex differences in rats with heart failure with preserved ejection fraction and the effect of autonomic modulation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Stavrakis ◽  
K Elkholey ◽  
L Morris ◽  
Y Li ◽  
S S Po
Keyword(s):  
Heart Failure ◽  
Sex Differences ◽  
Sudden Death ◽  
Ejection Fraction ◽  
Female Rats ◽  
Autonomic Modulation ◽  
Preserved Ejection Fraction ◽  
Qtc Prolongation ◽  
Male And Female ◽  
Male And Female Rats

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for 50% of HF and sudden death is the leading cause of mortality. There are considerable sex differences in cardiac structure and function, which may be related to outcomes in HFpEF. Transcutaneous vagus nerve stimulation (tVNS) is antiarrhythmic. Purpose To describe sex differences in mortality, autonomic tone and ECG parameters in rats with HFpEF and examine the effect of tVNS on these outcomes. Methods Dahl salt sensitive (DS) rats of either sex were randomized into high salt (HS, 8% NaCl) or low salt (LS) diet (0.3% NaCl) at 7 weeks of age. After 6 weeks of LS or HS diets, HS rats were randomized to receive active or sham tVNS, 30min daily (20Hz, 3mA) for 4 weeks. The rats were monitored daily for 4 weeks for the development of HFpEF. ECG and echocardiogram were performed at 13 weeks (baseline) and 17 weeks (endpoint). Heart rate variability (HRV) was calculated at the respective time points. ECG and HRV parameters were analyzed in a blinded fashion. Logistic regression analysis was performed to identify independent predictors of mortality. Results A total of 58 rats were included (5 male LS, 6 female LS, 22 male HS and 25 female HS). HS rats developed significant hypertension and signs of HFpEF, while 24% of females and 53% of males died (P=0.004). There were 4 sudden cardiac deaths in males (with ventricular tachycardia documented in 1 rat), whereas all the females died of HF or stroke. Corrected QT (QTc) at baseline significantly prolonged in HS compared to LS rats (250.5±14.4ms vs. 226.8±13.9ms, respectively, p=0.0007), while all other ECG parameters did not differ significantly between groups. In HS rats, QTc prolongation was significantly more pronounced in males compared to females (259.4±20.6ms vs. 243.8±14.5ms, respectively, P=0.002). In univariate analysis, prolonged baseline QTc (OR=1.04; 95% CI 1.01–1.06, p=0.003) and male sex (OR=3.21, 95% CI 1.19–8.66, p=0.016) predicted mortality. However, in multivariate analysis, QTc was the only significant predictor of mortality (OR=1.04; 95% CI 1.01–1.06, p=0.003). After 4 weeks of treatment, active tVNS significantly decreased QTc compared to sham (244.6±13.8ms vs. 255.8±14.0ms, respectively, p=0.017) in both male and female rats in a similar manner. The low frequency to high frequency ratio (LF/HF) of HRV, which reflects sympathovagal balance, was significantly decreased in active tVNS rats compared to sham (0.21±0.13 vs. 0.54±0.14, respectively; p=0.001) in both male and female rats in a similar manner. Conclusions Male rats with HFpEF exhibit worse survival compared to females and are at higher risk for sudden death. QTc prolongation accounts for the increased risk of sudden death in males compared to females. Autonomic modulation with tVNS attenuates the unfavorable changes in QTc and HRV induced by HS diet and may be used to prevent ventricular arrhythmias in patients with HFpEF.

Diet and 14CH3-Methionine Incorporation into Liver Phosphatidylcholine Fractions of Male and Female Rats

1971 ◽  
Vol 49 (1) ◽  
pp. 71-79 ◽  
Author(s):  
R. L. Lyman ◽  
G. Sheehan ◽  
J. Tinoco
Keyword(s):  
Sex Differences ◽  
Flaxseed Oil ◽  
Female Rats ◽  
Stock Diet ◽  
Choline Deficiency ◽  
Male And Female ◽  
Methyl Group ◽  
Degree Of Unsaturation ◽  
Male And Female Rats ◽  
Purina Chow

An experiment was conducted to see whether diet influenced the incorporation of 14CH3-methionine into liver phosphatidylcholines of male and female rats.Rats of both sexes were fed either a stock diet (Purina Chow), a semipurified diet containing 10% flaxseed oil, or a low methionine diet with or without choline. One hour before killing, 14CH3-methionine was injected into the animals. The distribution of the label in subfractions of liver phosphatidylcholines was then determined.Choline phosphatides of female rats fed chow or flaxseed oil diets had higher specific activities than did those of males. In chow-fed female rats the additional radioactivity appeared mainly in the tetraene phosphatidylcholine fraction. In female rats fed flaxseed oil, the extra label appeared in the tetraene as well as in a pentaene fraction.Therefore, changes in the degree of unsaturation of the species of phosphatidylcholine by dietary modification did not alter total incorporation of the label into liver phosphatidylcholines nor did it influence sex differences in the incorporation even though the distribution of the label within particular species of choline phosphatides was changed.No sex differences in incorporation were evident in the low methionine diet whether it contained choline or not. Choline deficiency did not affect total incorporation of the methyl group nor the proportions of phosphatidylcholine subfractions in the phospholipids, although in males it depressed the amount of hepatic phosphatidylcholine.

Sex Differences in Body-Weight Change following Gonadectomy of Rats

1968 ◽  
Vol 22 (2) ◽  
pp. 547-554 ◽  
Author(s):  
Jan W. Kakolewski ◽  
Verne C. Cox ◽  
Elliot S. Valenstein
Keyword(s):  
Body Weight ◽  
Sex Differences ◽  
Female Rats ◽  
Body Weight Change ◽  
Review Of The Literature ◽  
Male And Female ◽  
Male And Female Rats ◽  
Relationship Of ◽  
The Relationship ◽  
Hypothalamic Damage

Data are presented to demonstrate that the effects of gonadectomy on body weight and food consumption differ in male and female rats. The findings are related to the authors' report of sex differences in the effects of ventromedial hypothalamic damage. A review of the literature on the relationship of the gonads to body weight in different species is presented.

scholarly journals Sex differences in risk-taking and associative learning in rats

2015 ◽  
Vol 2 (11) ◽  
pp. 150485 ◽  
Author(s):  
Jolle Wolter Jolles ◽  
Neeltje J. Boogert ◽  
Ruud van den Bos
Keyword(s):  
Sex Differences ◽  
Learning Style ◽  
Risk Taking ◽  
Female Rats ◽  
Test Arena ◽  
Male And Female ◽  
New Associations ◽  
Time Out ◽  
Male And Female Rats ◽  
Predator Odour

In many species, males tend to have lower parental investment than females and greater variance in their reproductive success. Males might therefore be expected to adopt more high-risk, high-return behaviours than females. Next to risk-taking behaviour itself, sexes might also differ in how they respond to information and learn new associations owing to the fundamental link of these cognitive processes with the risk–reward axis. Here we investigated sex differences in both risk-taking and learned responses to risk by measuring male and female rats’ ( Rattus norvegicus ) behaviour across three contexts in an open field test containing cover. We found that when the environment was novel, males spent more time out of cover than females. Males also hid less when exposed to the test arena containing predator odour. By contrast, females explored more than males when the predator odour was removed (associatively learned risk). These results suggest that males are more risk-prone but behave more in line with previous experiences, while females are more risk-averse and more responsive to changes in their current environment. Our results suggest that male and female rats differ in how they cope with risk and highlight that a general link may exist between risk-taking behaviour and learning style.

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