Abstract 21: Sex Differences In Circadian Blood Pressure

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Bruna Visniauskas ◽  
Benard O Ogola ◽  
Isabella Kilanowski-doroh ◽  
Nicholas R Harris ◽  
Zaidmara T Diaz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Estrogen Receptors ◽  
Clock Genes ◽  
Strong Predictor ◽  
Circadian Variation ◽  
Circadian Disruption ◽  
Circadian Oscillation ◽  
Dependent Manner ◽  
Dark Cycle

Hypertensive patients frequently show a lack of 10% decline in nighttime (or nondipping) blood pressure (BP), which is a strong predictor of a cardiovascular event. Clock genes are essential regulators in diurnal BP in the vasculature during hypertension. However, little is known if vascular circadian clock factors influence BP rhythms in a sex-dependent manner. To test the hypothesis that AngII-induced hypertension disrupts the expression pattern of peripheral clock genes, male and female C57Bl/6J mice were subjected to AngII (700 ng/kg/min) infusion for two weeks. BP was measured by radiotelemetry (N=7/group). After two weeks, the animals were sacrificed during daytime or nighttime, and aortas were assessed for expression of clock genes (Per1, Per2, Bmal1) and estrogen receptors (ERα and GPER). Two-way ANOVA was used to compare light-dark cycle and AngII treatment effects. Hypertensive females (MAP: day 121 ± 9 vs. night 126 ± 10 mmHg, P=0.39; 7.3% dipping) but not males (MAP: day 128 ± 3 vs. night 140 ± 2 mmHg, P=0.01; >10% dipping) developed a non-dipping phenotype. AngII-hypertension amplified the circadian pattern of Per1 in the male aorta but removed the Per1 circadian variation in the female aorta. AngII did not alter Per2 oscillation in the aorta of either sex. Bmal1 patterns were also amplified in males and reversed in females. In response to AngII, aortic ERα expression was augmented during the day in females (control 287 ± 14 vs. AngII 413 ± 42 copies/ng RNA; P=0.01) but not in males (P=0.34). Furthermore, GPER expression exhibited a circadian oscillation in control (day 9 ± 1 vs. night 20 ± 7.6 copies/RNA ng) and hypertensive males (day 12 ± 17 vs. night 20 ± 5 copies/RNA ng, P=0.04), but not in females. In conclusion, sex differences exist in non-dipping BP patterns and circadian disruption of estrogen receptors and clock genes Per1 and Bmal1 in the vasculature after AngII treatment. This data suggest that females may be more vulnerable to circadian disruption during hypertension.

scholarly journals Bromide impairs the circadian clock and glycolytic homeostasis via disruption of autophagy in rat H9C2 cardiomyocytes

2019 ◽  
Author(s):  
Yicheng Jiang ◽  
Yang Gu ◽  
Hai Xu ◽  
Xiaoyi Tian ◽  
Xuefeng Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Viability ◽  
Circadian Clock ◽  
Mrna Expression ◽  
Clock Genes ◽  
Expression Patterns ◽  
Sodium Bromide ◽  
Circadian Oscillation ◽  
Dependent Manner ◽  
H9c2 Cardiomyocytes

Abstract Background Trace elements function as essential cofactors that are involved in various biochemical processes in mammals. Autophagy is vital for nutrient supplement, which is an important Zeitegber for the circadian homeostasis in heart. Here, we considered the possibility that autophagy, as well as the cardiomyocyte clock and glycolysis are interlinked. Detrimental effects were observed when cardiac system is exposed to bromine containing drugs. This study investigated the effects and mechanisms of bromide on the circadian clock and glycolytic metabolism of H9C2 cardiomyocytes. Methods H9C2 cardiomyocytes were incubated with sodium bromide at indicated doses for 24 hours, cell viability, mRNA expression of clock genes, glycolytic genes and autophagic genes were examined using various cellular and molecular approaches. Also, circadian oscillation rhythm of these genes was determined by serum shock with sodium bromide or equal amounts of sodium chloride. Results Bromide modestly affects cell viability and apoptosis of H9C2 cardiomyocytes. Bromide dampens the clock and glycolytic ( Hk2 and Pkm2 ) gene expression rhythmicity in a dose-dependent manner. Additionally, bromide inhibits autophagic process in H9C2 cardiomyocytes. In contrast, rapamycin (an autophagy inducer) dramatically restores the inhibitory effect of NaBr on the mRNA expression levels of clock genes ( Bmal1 , Cry1 and Rorα ) and glycolytic genes ( Hk2 and Pkm2 ). Conclusions Our results reveal that bromide represses the clock and glycolytic gene expression patterns, partially through inhibition of autophagy.

Abstract 049: Role of Smooth Muscle BMAL1 in Time-of-day Vasoconstriction Variation and Blood Pressure Circadian Rhythm

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Zhongwen Xie ◽  
Wen Su ◽  
Shu Liu ◽  
Guogang Zhao ◽  
Karyn Esser ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Circadian Rhythm ◽  
Pulse Pressure ◽  
Clock Genes ◽  
Time Of Day ◽  
Mesenteric Arteries ◽  
Dependent Manner ◽  
Central Pacemaker

The blood pressure circadian rhythm was believed to be primarily controlled by the central pacemaker suprachiasmatic nucleus (SCN). This dogma was challenged by the discoveries that each of the clock genes present in the SCN are also expressed and function in peripheral tissues. But whether, and if so how, the peripheral clock genes are involved remains uncertain. The current study investigates the role of Bmal1, an obligatory core clock gene, plays in smooth muscle and blood pressure regulation by using a smooth muscle specific BMAL1 knockout mouse model (SM-Bmal1-KO). The results show: 1) Smooth muscle specific deletion of BMAL1 does not affect the clock genes in SCN but drastically suppresses the amplitude and the time-of day differences in vasoconstriction in response to various agonist stimulation and to perfusion pressure increase in isolated small mesenteric arteries and pressor responses in anesthetized mice; 2) The inhibition of agonist-induced vasoconstriction is associated with suppression of MLC 20 phosphorylation, ROCK2 mRNA and activity. Moreover, BMAL1 directly binds to ROCK2 promoter in a time-of-day dependent manner in mesenteric arteries and is required for ROCK2 promoter activity in cultured vascular smooth muscle cells; 3) Mice lacking smooth muscle BMAL1, but not those lacking cardiomyocyte BMAL1, exhibits alterations in blood pressure. SM-Bmal1-KO mice have moderately but significantly decreased blood pressure under 12:12 light/dark cycle, constant dark, and constant light conditions. The blood pressure circadian rhythm in SM-Bmal1-KO mice has diminished amplitude, forward shifted acrophase, but normal period length and normal locomotor activity; 4) interestingly, pulse pressure is markedly elevated and the pulse pressure circadian rhythm is abolished in the SM-Bmal1-KO mice. These data provide novel mechanistic insights into the daily control of vasoconstriction and blood pressure, which are fundamentally significant for the elucidation of pathogenesis of diseases involving blood pressure circadian rhythm disruption.

scholarly journals High-fat diet and estrogen impacts the colon and its transcriptome in a sex-dependent manner

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
L. Hases ◽  
A. Archer ◽  
R. Indukuri ◽  
M. Birgersson ◽  
C. Savva ◽  
...  
Keyword(s):  
Sex Differences ◽  
High Fat Diet ◽  
Clock Genes ◽  
Control Diet ◽  
Macrophage Infiltration ◽  
Dependent Manner ◽  
High Fat ◽  
Selective Activation ◽  
The Metabolic Syndrome ◽  
The Impact

Abstract There is a strong association between obesity and colorectal cancer (CRC), especially in men, whereas estrogen protects against both the metabolic syndrome and CRC. Colon is the first organ to respond to high-fat diet (HFD), and estrogen receptor beta (ERβ) can attenuate CRC development. How estrogen impacts the colon under HFD and related sex differences has, however, not been investigated. To dissect this, mice were fed control diet or HFD for 13 weeks and administered receptor-selective estrogenic ligands for the last three weeks. We recorded impact on metabolism, colon crypt proliferation, macrophage infiltration, and the colon transcriptome. We found clear sex differences in the colon transcriptome and in the impact by HFD and estrogens, including on clock genes. ERα-selective activation reduced body weight and generated systemic effects, whereas ERβ-selective activation had local effects in the colon, attenuating HFD-induced macrophage infiltration and epithelial cell proliferation. We here demonstrate how HFD and estrogens modulate the colon microenvironment in a sex- and ER-specific manner.

scholarly journals Bromide impairs the circadian clock and glycolytic homeostasis via disruption of autophagy in rat H9C2 cardiomyocytes

2020 ◽  
Author(s):  
Yicheng Jiang ◽  
Yang Gu ◽  
Hai Xu ◽  
Xiaoyi Tian ◽  
Xuefeng Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Viability ◽  
Circadian Clock ◽  
Mrna Expression ◽  
Clock Genes ◽  
Expression Patterns ◽  
Sodium Bromide ◽  
Circadian Oscillation ◽  
Dependent Manner ◽  
H9c2 Cardiomyocytes

Abstract Background: Trace elements function as essential cofactors that are involved in various biochemical processes in mammals. Autophagy is vital for nutrient supplement, which is an important Zeitegber for the circadian homeostasis in heart. Here, we considered the possibility that autophagy, as well as the cardiomyocyte clock and glycolysis are interlinked. Detrimental effects were observed when cardiac system is exposed to bromine containing drugs. This study investigated the effects and mechanisms of bromide on the circadian clock and glycolytic metabolism of H9C2 cardiomyocytes. Methods: H9C2 cardiomyocytes were incubated with sodium bromide at indicated doses for 24 hours, cell viability, mRNA expression of clock genes, glycolytic genes and autophagic genes were examined using various cellular and molecular approaches. Also, circadian oscillation rhythm of these genes was determined by serum shock with sodium bromide or equal amounts of sodium chloride. Results: Bromide does not affect cell viability and apoptosis of H9C2 cardiomyocytes. Bromide dampens the clock and glycolytic ( Hk2 and Pkm2 ) gene expression rhythmicity in a dose-dependent manner. Additionally, bromide inhibits autophagic process in H9C2 cardiomyocytes. In contrast, rapamycin (an autophagy inducer) dramatically restores the inhibitory effect of NaBr on the mRNA expression levels of clock genes ( Bmal1 , Cry1 and Rorα ) and glycolytic genes ( Hk2 and Pkm2 ).Conclusions: Our results reveal that bromide represses the clock and glycolytic gene expression patterns, partially through inhibition of autophagy.

Sex Differences in Cardiovascular Reactivity

2009 ◽  
Vol 23 (2) ◽  
pp. 77-84 ◽  
Author(s):  
Matthew C. Whited ◽  
Kevin T. Larkin
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sex Differences ◽  
Gender Roles ◽  
Cardiovascular Reactivity ◽  
Task Type ◽  
Conflict Task ◽  
Men And Women ◽  
Conflicting Evidence ◽  
Blood Pressure Responses

Sex differences in cardiovascular reactivity to stress are well documented, with some studies showing women having greater heart rate responses than men, and men having greater blood pressure responses than women, while other studies show conflicting evidence. Few studies have attended to the gender relevance of tasks employed in these studies. This study investigated cardiovascular reactivity to two interpersonal stressors consistent with different gender roles to determine whether response differences exist between men and women. A total of 26 men and 31 women were assigned to either a traditional male-oriented task that involved interpersonal conflict (Conflict Task) or a traditional female-oriented task that involved comforting another person (Comfort Task). Results demonstrated that women exhibited greater heart rate reactions than men independent of the task type, and that men did not display a higher reactivity than women on any measure. These findings indicate that sex of participant was more important than gender relevance of the task in eliciting sex differences in cardiovascular responding.

Smoking, Serum Lipids, Blood Pressure, and Sex Differences in Myocardial Infarction

Circulation ◽  
1996 ◽  
Vol 93 (3) ◽  
pp. 450-456 ◽  
Author(s):  
Inger Njølstad ◽  
Egil Arnesen ◽  
Per G. Lund-Larsen
Keyword(s):  
Myocardial Infarction ◽  
Blood Pressure ◽  
Sex Differences ◽  
Serum Lipids

scholarly journals Understanding sex differences in long-term blood pressure regulation: insights from experimental studies and computational modeling

2019 ◽  
Vol 316 (5) ◽  
pp. H1113-H1123 ◽  
Author(s):  
Sameed Ahmed ◽  
Rui Hu ◽  
Jessica Leete ◽  
Anita T. Layton
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Computational Models ◽  
Experimental Studies ◽  
Pressure Control ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Physiological Processes ◽  
Key Players

Sex differences in blood pressure and the prevalence of hypertension are found in humans and animal models. Moreover, there has been a recent explosion of data concerning sex differences in nitric oxide, the renin-angiotensin-aldosterone system, inflammation, and kidney function. These data have the potential to reveal the mechanisms underlying male-female differences in blood pressure control. To elucidate the interactions among the multitude of physiological processes involved, one may apply computational models. In this review, we describe published computational models that represent key players in blood pressure regulation, and highlight sex-specific models and their findings.

scholarly journals Blood Pressure-Lowering Effect of Wine Lees Phenolic Compounds Is Mediated by Endothelial-Derived Factors: Role of Sirtuin 1

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1073
Author(s):  
Raúl López-Fernández-Sobrino ◽  
Jorge R. Soliz-Rueda ◽  
Javier Ávila-Román ◽  
Anna Arola-Arnal ◽  
Manuel Suárez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Sirtuin 1 ◽  
Dependent Manner ◽  
Blood Pressure Lowering Effect ◽  
Synthesis Inhibitor ◽  
Spontaneously Hypertensive ◽  
Lowering Effect ◽  
Pressure Lowering ◽  
Endothelial Gene Expression

The antihypertensive effect of wine lees powder (WLPW) from a Cabernet grape variety was related to its high content in flavanols and anthocyanins compounds. This study investigates the involvement of endothelial-derived factors and SIRT1 in its bioactivity. Spontaneously hypertensive rats (SHR) were orally administered water or WLPW (125 mg/kg bw). Posteriorly, both groups were intraperitoneally administered saline, Nω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthesis inhibitor, indomethacin, a prostacyclin synthesis inhibitor, or sirtinol, an inhibitor of sirtuins. Blood pressure (BP) was recorded before and 6 h after WLPW administration. In an additional experiment, SHR were administered water or WLPW and endothelial expressions of eNos, Sirt1, Nox4, and Et1 were determined. The BP-lowering properties of WLPW were abolished by L-NAME and partially reduced by indomethacin, demonstrating that WLPW antihypertensive effect was mediated by changes in NO availability, although prostacyclin also contributed to this activity. Moreover, BP-lowering effect was reduced by sirtinol, indicating that WLPW decreased BP in a SIRT1-dependent manner. Furthermore, WLPW upregulated eNos and Sirt1 and downregulated Nox4 and Et1 endothelial gene expression. These results evidence the vasoprotective effect of WLPW and show that its antihypertensive effect in SHR is endothelium dependent and mediated by SIRT1.

scholarly journals Sex differences in the association between major cardiovascular risk factors in midlife and dementia: a cohort study using data from the UK Biobank

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jessica Gong ◽  
Katie Harris ◽  
Sanne A. E. Peters ◽  
Mark Woodward
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Sex Differences ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Sex Difference ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Uk Biobank ◽  
The Uk

Abstract Background Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). Methods Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. Results 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62–6.16] for women and 8.42 [8.07–8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77–0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02–1.13] in women and 0.98 [0.93–1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer’s disease). Conclusions Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.

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