Two New Studies Look at Role of Personality and Work Demands in Health and Safety on the Job: Differences in Work Injury Among Male and Female Firefighters Examined; Link Found Between Industrial Noise and Increased Worker's Blood Pressure

Angiotensin II acting via Angiotensin II type 2 receptors (AT2Rs) is believed to be protective against blood pressure increase and affects renal function under pathophysiological condition. Recently we have observed that stimulation of AT2Rs in male obese Zucker rats has shifted the two opposing arms of renin angiotensin system (RAS) i.e. ACE-Ang II-AT1 vs ACE2/Ang-(1-7)-Mas. Evidence suggests that estrogen regulates RAS, including AT2R in female mice. We hypothesized that AT2R has a gender specific regulation of RAS. In the present study, we investigated the role of AT2Rs in regulating RAS components in male and female mice. Kidney cortex from AT2R knockout (AT2RKO) male and female mice and wild type (WT) with similar background (C57BL/6) of 20 weeks of age were used in the study. The cortical ACE expression (ng ACE/μg tissue) was significantly increased in AT2RKO mice (3±0.02) compared to WT males (1.9±0.02). LC/MS analysis of cortical tissue revealed that Ang II was also significantly increased in AT2RKO mice (WT: 31±3, AT2RKO: 47±3 fmoles/mg tissue). Deletion of AT2R significantly increased AT1R (204%, 204 of 100) expression and had no effect on renin activity compared to WT males. The cortical expression of ACE2 activity (WT: 113±8, AT2RKO: 40±11, RFU/min), Ang-(1-7) levels (WT: 7.3±1.4, AT2RKO: 3±0.8 fmoles/mg tissue) and Mas receptor (AT2RKO: 54±15, % of WT) was significantly decreased in AT2RKO males compared to WT. The cortical expression of the AT2R and MasR was 2-fold greater in WT females compared to WT male. The renin activity (WT: 32±2, AT2RKO: 21±0.3, RFU/min) and MasR expression (WT: 187.5±55, AT2KO: 47±9) was significantly decreased in AT2RKO females compared to the female WT. Interestingly, Ang-(1-7) level (WT: 5.7±0.7, AT2RKO 2.6±0.7 fmoles/mg tissue) was decreased but no changes in ACE or ACE2 activity was observed in AT2KO females compared to their WT, suggesting a role of non-ACE2 pathway. This study suggests that AT2R regulates ACE/ACE2 ratio-Ang II-AT1R expression negatively only in males, whereas in females, it regulates Ang-(1-7) potentially via non-ACE2 pathway. Such changes indicate a gender specific mechanisms potentially associated with AT2R-mediated regulation of renal function and blood pressure control.

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Impact of Mineralocorticoid Receptor And Angiotensin Ii Type 1 Receptor Antagonism on Blood Pressure Regulation in Obese Zucker Rats: Role of Sex Differences

American Journal of Hypertension ◽

10.1093/ajh/hpaa170 ◽

2020 ◽

Author(s):

Jussara M do Carmo ◽

Alexandre A da Silva ◽

John E Hall

Keyword(s):

Blood Pressure ◽

Sex Differences ◽

Mineralocorticoid Receptor ◽

Combined Treatment ◽

Zucker Rats ◽

Male And Female ◽

Obese Zucker Rats ◽

Males And Females

Abstract Background Previous studies suggest that obesity-induced hypertension in females, but not males, is due to leptin-mediated stimulation of aldosterone secretion and subsequent activation of the mineralocorticoid receptor (MR). Although angiotensin II type 1 receptor (AT1R) antagonism lowers blood pressure (BP) in male obese Zucker rats (OZR), which have defective leptin signaling, the potential role of sex differences in BP responses to RAAS blockade, including MR antagonism, in obesity is still unclear. We tested the cardiovascular effects of MR antagonism, alone or in combination with AT1R blockade in male and female OZR (n=5/sex) and lean Zucker rats (LZR, n=7/sex). Methods BP and heart rate (HR) were measured by telemetry 24-hrs/day. After a 6-day control period, spironolactone (40 mg/kg/day) was given for 10 days followed by a 7-day combined treatment with losartan (20 mg/kg/day), and followed by 6-day post-treatment recovery period. Results Compared to lean rats, OZR were hypertensive (Mean arterial pressure: 115±4 vs. 104±2 and 111±s vs. 100±3 mmHg for males and females) and had lower HR (355±9 vs. 393±7 and 367±10 vs. 412±13 bpm). MR blockade alone did not alter BP or HR in lean or obese male and female Zucker rats, whereas combined treatment reduced BP in obese and lean rats by 31±3 vs. 21±1 and 8±1 vs. 5±1 mmHg in males and females, respectively. No changes were observed in HR. Conclusions These results suggest that there are important sex differences in BP responses to chronic AT1R blockade but no major involvement of MR activation in BP regulation in OZR.

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Splenectomy decreases blood pressure and abolishes sex differences in renal Tregs in spontaneously hypertensive rats

Clinical Science ◽

10.1042/cs20210469 ◽

2021 ◽

Author(s):

Ellen E Gillis ◽

Kasey Belanger ◽

Mahmoud Abdelbary ◽

Riyaz Mohamed ◽

Jingping Sun ◽

...

Keyword(s):

Blood Pressure ◽

T Cells ◽

Sex Differences ◽

Spontaneously Hypertensive Rats ◽

Flow Cytometric Analysis ◽

Hypertensive Rats ◽

Male And Female ◽

Spontaneously Hypertensive ◽

Flow Cytometric

Over the past decade there has been increasing support for a role of the immune system in the development of hypertension. Our lab has previously reported that female spontaneously hypertensive rats (SHR) have a blood pressure (BP)-dependent increase in anti-inflammatory renal regulatory T cells (Tregs), corresponding to lower BP compared to males. However, little is known regarding the mechanism for greater renal Tregs in females. The current study was designed to test the hypothesis that the greater relative abundance of renal Tregs in female SHR is due to greater Treg production. To test this hypothesis, T cell profiles were measured in the spleen by flow cytometry in male and female SHR at 5 weeks and 14 weeks of age. Splenic Tregs did not differ between males and females, suggesting sex differences in renal Tregs is not due to differences in production. To assess the role of the spleen in sex differences in renal Tregs and BP control, rats were randomized to receive sham surgery (CON) or splenectomy (SPLNX, n=6) at 12 wks of age and implanted with telemeters to measure BP. After 2 weeks, kidneys were harvested for flow cytometric analysis of T cells. Splenectomy increased BP in both sexes after 2 weeks. Renal Tregs decreased in both sexes after splenectomy, abolishing the sex differences in renal Tregs. In conclusion, splenic Tregs were comparable in male and female SHR, suggesting that sex differences in renal Tregs is due to differences in renal Treg recruitment, not Treg production.

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Abstract P314: Effect of Sex on Blood Pressure and Endothelial Dysfunction in the Novel BPH2 Mouse Model of Hypertension

Hypertension ◽

10.1161/hyp.70.suppl_1.p314 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Sean P Didion

Keyword(s):

Blood Pressure ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Renin Angiotensin System ◽

Similar Degree ◽

The Novel ◽

Angiotensin System ◽

Male And Female ◽

Renin Angiotensin

Very little is known regarding blood pressure and endothelial function between the sexes in the hypertensive BPH2 mouse. Thus, the first goal was determine whether blood pressure and endothelial function are significantly different between male and female BPH2 mice. Information regarding the role of the renin-angiotensin system in the BPH2 mouse is also limited; therefore the second goal was to determine the role of the renin-angiotensin system by treating BPH2 mice with captopril for 4 weeks. Systolic blood pressure (SBP) was significantly elevated (P<0.05) and yet comparable (P>0.05) in male and female BPH2 mice and averaged 140±3 and 136±3 mmHg, respectively, whereas, in control mice SBP averaged 112±4 mmHg. Endothelial responses to acetylcholine in carotid artery were markedly impaired (P<0.05) and to a similar degree in male and female BPH2 mice as compared to controls. Captopril treatment was associated with a significant (P<0.05) reduction in blood pressure of 35±7 and 43±4 mmHg in male and female BPH2 mice, respectively. Captopril also resulted in an improvement of endothelial responses in male and female BPH2 mice. These findings demonstrate that male and female BPH2 mice are equally hypertensive and both sexes are characterized by endothelial dysfunction. In addition, the renin-angiotensin system may contribute to both hypertension and endothelial dysfunction in this model. Taken together, our data define the BPH2 mouse as an important model to compare and contrast the effects of hypertension between the sexes. Supported by NIH HL-107632.

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Human Stool Metabolome Differs upon 24 h Blood Pressure Levels and Blood Pressure Dipping Status: A Prospective Longitudinal Study

Metabolites ◽

10.3390/metabo11050282 ◽

2021 ◽

Vol 11 (5) ◽

pp. 282

Author(s):

Justine Huart ◽

Arianna Cirillo ◽

Bernard Taminiau ◽

Julie Descy ◽

Annie Saint-Remy ◽

...

Keyword(s):

Blood Pressure ◽

Short Chain Fatty Acids ◽

Prospective Longitudinal Study ◽

Male And Female ◽

Entire Cohort ◽

Female Partners ◽

Stool Samples ◽

Prospective Longitudinal

Dysbiosis of gut microbiota (GM) has been involved in the pathophysiology of arterial hypertension (HT), via a putative role of short chain fatty acids (SCFAs). Its role in the circadian regulation of blood pressure (BP), also called “the dipping profile”, has been poorly investigated. Sixteen male volunteers and 10 female partners were subjected to 24 h ambulatory BP monitoring and were categorized in normotensive (NT) versus HT, as well as in dippers versus non-dippers. Nuclear magnetic resonance (NMR)-based metabolomics was performed on stool samples. A 5-year comparative follow-up of BP profiles and stool metabolomes was done in men. Significant correlations between stool metabolome and 24 h mean BP levels were found in both male and female cohorts and in the entire cohort (R2 = 0.72, R2 = 0.79, and R2 = 0.45, respectively). Multivariate analysis discriminated dippers versus non-dippers in both male and female cohorts and in the entire cohort (Q2 = 0.87, Q2 = 0.98, and Q2 = 0.68, respectively). Fecal amounts of acetate, propionate, and butyrate were higher in HT versus NT patients (p = 0.027; p = 0.015 and p = 0.015, respectively), as well as in non-dippers versus dippers (p = 0.027, p = 0.038, and p = 0.036, respectively) in the entire cohort. SCFA levels were significantly different in patients changing of dipping status over the 5-year follow-up. In conclusion, stool metabolome changes upon global and circadian BP profiles in both genders.

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Prenatal exposure to Bisphenols affects blood pressure in both male and female offspring: Differential role of Ang II

The FASEB Journal ◽

10.1096/fasebj.2021.35.s1.05440 ◽

2021 ◽

Vol 35 (S1) ◽

Author(s):

Maryam Al Mansi ◽

YenJun Chuang ◽

Amrita Kaimal ◽

Ninitha Jeyaraj ◽

Puliyur MohanKumar ◽

...

Keyword(s):

Blood Pressure ◽

Prenatal Exposure ◽

Female Offspring ◽

Ang Ii ◽

Male And Female

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Abstract P076: Suppressor of Cytokine Signaling 3 (SOCS3) in POMC Neurons and Its Role in Regulating Blood Pressure, Body Weight and Glucose in Obesity

Hypertension ◽

10.1161/hyp.66.suppl_1.p076 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Zhen Wang ◽

Jussara M do Carmo ◽

Alexandre A da Silva ◽

John E Hall

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Food Intake ◽

Negative Regulator ◽

Cytokine Signaling ◽

Suppressor Of Cytokine Signaling ◽

Male And Female ◽

Female Mice ◽

And Control

Suppressor of cytokine signaling 3 (SOCS3), a negative regulator of leptin signaling, may be involved in development of obesity-induced leptin resistance. Although we previously showed that activation of proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on blood pressure (BP), the role of SOCS3 in modulating BP in obesity is still unclear. In this study, we investigated the role of SOCS3 specifically in POMC neurons in regulating body weight, glucose handling and BP in mice fed a normal or high fat (45%, HFD) chow. Male and female SOCS3flox/flox-POMC/cre mice in which SOCS3 was selectively deleted in POMC neurons and control SOCS3flox/flox mice were used. Food intake and body weight were measured from 8 to 16 weeks of age, and a glucose tolerance test (GTT) was performed at 20 wks of age. At 22 wks of age, mice were implanted with telemetry probe to measure BP and heart rate (HR) and fed a HFD for 6 weeks. Compared to control mice, both male and female SOCS3flox/flox-POMC/cre mice were lighter at 16 wks (29.1 ± 3.5 vs 31.9 ± 3.6 g in male and 21.5 ± 2.2 vs 26.1 ± 5.7 in female, n=9-11, p<0.05) but food intake was similar in both groups. Only male SOCS3flox/flox-POMC/cre mice exhibited improved glucose handling (AUC: 1059 ± 52 vs 1283 ± 54 mg/dL x 120 min, n=7-10, p<0.05 ) and no differences were observed in female mice. When fed normal chow, BP was similar in SOCS3flox/flox-POMC/cre and control mice (116 ± 7 vs 113 ± 5 mmHg) at 23 wks. After a HFD for 6 weeks, SOCS3flox/flox-POMC/cre mice had a greater BP increase compared to control mice (7.2 ± 1.9 vs 0.9 ± 1.8 mmHg, n=4-9, P<0.05) but no significant differences were observed in food intake or body weight between two groups. These results suggest that SOCS3 deletion specifically in POMC neurons reduced body weight in male and female mice, and improved glucose handling only in male mice. HFD increased BP in SOCS3flox/flox-POMC/cre but not in control mice, suggesting that SOCS3 in POMC neurons may modulate BP response to HFD.

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