scholarly journals Review 1: The salivary protein BPIFA2 differentially regulates sodium preference and blood pressure and in male and female mice

2020 ◽  
Author(s):  
Romana Stopková
Keyword(s):  
Blood Pressure ◽  
Salivary Protein ◽  
Male And Female ◽  
Female Mice

scholarly journals The salivary protein BPIFA2 differentially regulates sodium preference and blood pressure in male and female mice

2020 ◽  
Vol 1 ◽  
Author(s):  
Sven-Ulrik Gorr
Keyword(s):  
Blood Pressure ◽  
Knockout Mice ◽  
Salivary Protein ◽  
Binding Activity ◽  
Wild Type ◽  
Male And Female ◽  
Knockout Mouse Model ◽  
Spontaneously Hypertensive ◽  
Female Mice ◽  
Lps Binding

AbstractBPIFA2 (PSP, SPLUNC2, C20orf70) is a major salivary protein of uncertain physiological function. BPIFA2 is downregulated in salivary glands of spontaneously hypertensive rats, pointing to a role in blood pressure regulation. This study used a novel Bpifa2 knockout mouse model to test the role of BPIFA2 in sodium preference and blood pressure. Blood pressure did not differ between wild-type male and female mice but was significantly lower in male knockout mice compared to male wild-type mice. In contrast, blood pressure was increased in female knockout mice compared to female wild-type mice. Female wild-type mice showed a significant preference for 0.9% saline compared to male mice. This difference was reduced in the knockout mice. BPIFA2 is an LPS-binding protein but it remains to be determined if the reported effects are mediated by the LPS-binding activity of BPIFA2.

Abstract 096: Leptin and High Salt Diet Induce Greater Increases in Blood Pressure in Female than Male Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jessica L Faulkner ◽  
Eric J Belin de Chantemele
Keyword(s):  
Blood Pressure ◽  
Recovery Period ◽  
Pressure Rise ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Male And Female ◽  
Female Mice ◽  
Males And Females ◽  
Blood Pressure Responses

Recent studies by our group demonstrated that leptin is a direct regulator of aldosterone secretion and increases blood pressure via sex-specific mechanisms involving leptin-mediated activation of the aldosterone-mineralocorticoid receptor signaling pathway in females and sympatho-activation in males. Although it is well accepted that females secrete more leptin and aldosterone than males, it is unknown whether leptin infusion raises blood pressure similarly in male and female mice and whether higher aldosterone levels sensitize females to salt-induced hypertension. We hypothesized that female mice would be more sensitive to leptin than males and also have a potentiated blood pressure rise in response to high salt diet compared to males. Male and female Balb/C mice were implanted with radiotelemeters for continuous measurement of mean arterial pressure (MAP) at 10 weeks of age. MAP was measured for seven days prior to feeding with a high-salt diet (HS, 4%NaCl) for seven days. Following a recovery period, animals were then implanted with osmotic minipumps containing leptin (0.9mg/kg/day) recorded for seven days. Baseline MAP was similar between males and females (101.3±2.9 vs 99.3±3.7 mmHg, n=4 and 5, respectively), however, HS diet resulted in a greater MAP increase in females (15.0±2.6 mmHg) compared to males (3.1±4.5 mmHg, P<0.05). MAP with leptin treatment was increased with leptin in females moreso than in males, however, this did not reach significance (6.8±5.8 vs 1.8±5.9 mmHg, respectively). This potential sex difference in blood pressure responses to leptin was not associated with changes in body weight (0.07±0.44 vs -0.22±0.2 g, respectively) nor changes in blood glucose (-19.67±15.06 vs -15.4±11.4 mg/dl, respectively) in males and females in response to leptin. In summary, female mice are more sensitive to HS diet-induced blood pressure increases than males. Females may be more sensitive to leptin-mediated blood pressure increases than males. Further investigation is needed to determine whether these sex differences in blood pressure responses to HS diet and leptin are mediated by aldosterone or other mechanisms.

Abstract 7: Angiotensin II Type 2 Receptor Deficiency Increases Renal ACE/ACE2 Ratio-Ang II-AT1R Expression In Male but not in Female Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Quaisar Ali ◽  
Yonnie Wu ◽  
Tadashi Inagami ◽  
Tahir Hussain
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Angiotensin Ii ◽  
Renin Activity ◽  
Ang Ii ◽  
Male And Female ◽  
Female Mice ◽  
Gender Specific

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.

HIV Increases Basal Metabolic Rate, Impairs Endothelial Function and Elevates Blood Pressure in Male and Female Mice

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Taylor C. Kress ◽  
Thiago Bruder Nascimento ◽  
Simone Kennard ◽  
Derrian Wright ◽  
Jessica L. Faulkner ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Function ◽  
Metabolic Rate ◽  
Basal Metabolic Rate ◽  
Male And Female ◽  
Female Mice

scholarly journals Differences in renal BMAL1 contribution to Na+ homeostasis and blood pressure control in male and female mice

2020 ◽  
Vol 318 (6) ◽  
pp. F1463-F1477 ◽  
Author(s):  
G. Ryan Crislip ◽  
Lauren G. Douma ◽  
Sarah H. Masten ◽  
Kit-Yan Cheng ◽  
I. Jeanette Lynch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Blood Pressure Control ◽  
Collecting Duct ◽  
Pressure Control ◽  
Thick Ascending Limb ◽  
Restricted Diet ◽  
Male And Female ◽  
Female Mice ◽  
Genotype Difference

The renal circadian clock has a major influence on the function of the kidney. Aryl hydrocarbon receptor nuclear translocator-like protein 1 [ARNTL; also known as brain and muscle ARNT-like 1 (BMAL1)] is a core clock protein and transcription factor that regulates the expression of nearly half of all genes. Using male and female kidney-specific cadherin BMAL1 knockout (KS-BMAL1 KO) mice, we examined the role of renal distal segment BMAL1 in blood pressure control and solute handling. We confirmed that this mouse model does not express BMAL1 in thick ascending limb, distal convoluted tubule, and collecting duct cells, which are the final locations for solute and fluid regulation. Male KS-BMAL1 KO mice displayed a substantially lower basal systolic blood pressure compared with littermate control mice, yet their circadian rhythm in pressure remained unchanged [male control mice: 127 ± 0.7 mmHg ( n = 4) vs. male KS-BMAL KO mice: 119 ± 2.3 mmHg ( n = 5), P < 0.05]. Female mice, however, did not display a genotype difference in basal systolic blood pressure [female control mice: 120 ± 1.6 mmHg ( n = 5) vs. female KS-BMAL1 KO mice: 119 ± 1.5 mmHg ( n = 7), P = 0.4]. In addition, male KS-BMAL1 KO mice had less Na+ retention compared with control mice in response to a K+-restricted diet (15% less following 5 days of treatment). However, there was no genotype difference in Na+ handling after a K+-restricted diet in female mice. Furthermore, there was evidence indicating a sex-specific response to K+ restriction where female mice reabsorbed less Na+ in response to this dietary challenge compared with male mice. We propose that BMAL1 in the distal nephron and collecting duct contributes to blood pressure regulation and Na+ handling in a sex-specific manner.

scholarly journals Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice

2017 ◽  
Vol 312 (3) ◽  
pp. H459-H468 ◽  
Author(s):  
Yu Wang ◽  
Robin Shoemaker ◽  
David Powell ◽  
Wen Su ◽  
Sean Thatcher ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Ang Ii ◽  
Wild Type ◽  
Male And Female ◽  
Reduced Ejection Fraction ◽  
Female Mice ◽  
Induced Hypertension ◽  
Blood Pressures

Angiotensin-(1–7) [ANG-(1–7)] acts at Mas receptors (MasR) to oppose effects of angiotensin II (ANG II). Previous studies demonstrated that protection of female mice from obesity-induced hypertension was associated with increased systemic ANG-(1–7), whereas male obese hypertensive mice exhibited increased systemic ANG II. We hypothesized that MasR deficiency ( MasR−/−) augments obesity-induced hypertension in males and abolishes protection of females. Male and female wild-type ( MasR+/+) and MasR−/− mice were fed a low-fat (LF) or high-fat (HF) diet for 16 wk. MasR deficiency had no effect on obesity. At baseline, male and female MasR−/− mice had reduced ejection fraction (EF) and fractional shortening than MasR+/+ mice. Male, but not female, HF-fed MasR+/+ mice had increased systolic and diastolic (DBP) blood pressures compared with LF-fed controls. In HF-fed females, MasR deficiency increased DBP compared with LF-fed controls. In contrast, male HF-fed MasR−/− mice had lower DBP than MasR+/+ mice. We quantified cardiac function after 1 mo of HF feeding in males of each genotype. HF-fed MasR−/− mice had higher left ventricular (LV) wall thickness than MasR+/+ mice. Moreover, MasR+/+, but not MasR−/−, mice displayed reductions in EF from HF feeding that were reversed by ANG-(1–7) infusion. LV fibrosis was reduced in HF-fed MasR+/+ but not MasR−/− ANG-(1–7)-infused mice. These results demonstrate that MasR deficiency promotes obesity-induced hypertension in females. In males, HF feeding reduced cardiac function, which was restored by ANG-(1–7) in MasR+/+ but not MasR−/− mice. MasR agonists may be effective therapies for obesity-associated cardiovascular conditions. NEW & NOTEWORTHY MasR deficiency abolishes protection of female mice from obesity-induced hypertension. Male MasR-deficient obese mice have reduced blood pressure and declines in cardiac function. ANG-(1–7) infusion restores obesity-induced cardiac dysfunction of wild-type, but not MasR-deficient, male mice. MasR agonists may be cardioprotective in obese males and females.

scholarly journals Female and male mice have differential longterm cardiorenal outcomes following a matched degree of ischemia–reperfusion acute kidney injury

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Danielle E. Soranno ◽  
Peter Baker ◽  
Lara Kirkbride-Romeo ◽  
Sara A. Wennersten ◽  
Kathy Ding ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Acute Kidney Injury ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Cardiovascular Outcomes ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice

AbstractAcute kidney injury (AKI) is common in patients, causes systemic sequelae, and predisposes patients to long-term cardiovascular disease. To date, studies of the effects of AKI on cardiovascular outcomes have only been performed in male mice. We recently demonstrated that male mice developed diastolic dysfunction, hypertension and reduced cardiac ATP levels versus sham 1 year after AKI. The effects of female sex on long-term cardiac outcomes after AKI are unknown. Therefore, we examined the 1-year cardiorenal outcomes following a single episode of bilateral renal ischemia–reperfusion injury in female C57BL/6 mice using a model with similar severity of AKI and performed concomitantly to recently published male cohorts. To match the severity of AKI between male and female mice, females received 34 min of ischemia time compared to 25 min in males. Serial renal function, echocardiograms and blood pressure assessments were performed throughout the 1-year study. Renal histology, and cardiac and plasma metabolomics and mitochondrial function in the heart and kidney were evaluated at 1 year. Measured glomerular filtration rates (GFR) were similar between male and female mice throughout the 1-year study period. One year after AKI, female mice had preserved diastolic function, normal blood pressure, and preserved levels of cardiac ATP. Compared to males, females demonstrated pathway enrichment in arginine metabolism and amino acid related energy production in both the heart and plasma, and glutathione in the plasma. Cardiac mitochondrial respiration in Complex I of the electron transport chain demonstrated improved mitochondrial function in females compared to males, regardless of AKI or sham. This is the first study to examine the long-term cardiac effects of AKI on female mice and indicate that there are important sex-related cardiorenal differences. The role of female sex in cardiovascular outcomes after AKI merits further investigation.

scholarly journals Regulation of Blood Pressure and Renal Fibrosis by Class I Specific HDAC Inhibitor, Mocetinostat, in Npr1 Gene‐targeted Male and Female Mice

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Prerna Kumar ◽  
Kandasamy Neelamegam ◽  
Ramachandran Samivel ◽  
Huijing Xia ◽  
Chandramohan Ramasamy ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Hdac Inhibitor ◽  
Renal Fibrosis ◽  
Class I ◽  
Male And Female ◽  
Female Mice ◽  
Regulation Of Blood Pressure ◽  
Npr1 Gene

Abstract MP27: Adipose-derived Human Soluble (Pro)renin Receptor Causes Resistance To Losartan Treatment In High-Fat Diet Male And Female Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Kellea Nichols ◽  
Audrey Poupeau ◽  
Eva Gatineau ◽  
Gertrude Arthur ◽  
Frederique B Yiannikouris
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
High Fat Diet ◽  
Partial Agonist ◽  
High Fat ◽  
Male And Female ◽  
Female Mice ◽  
Critical Gap ◽  
Prorenin Receptor ◽  
Obesity Hypertension

Obesity, affecting more that 37% of the US, contributes to hypertension. Despite the use of one or more anti-hypertensive treatments, 48% of the hypertensive population remains with resistant hypertension, which prompts the development for new therapeutic targets. We demonstrated that obesity increased the expression of prorenin receptor (PRR) in the adipose tissue and elevated plasma soluble PRR (sPRR). In addition, the infusion of mouse sPRR increased blood pressure in male mice fed high fat-diet (HF); indicating that adipose-derived sPRR could increase circulating sPRR and contribute to hypertension. However, there is a critical gap in the functional role of human sPRR in obesity-hypertension. In this study, we aim to define whether adipose-derived human sPRR contributes to obesity-hypertension. Human sPRR-Myc-tag transgenic mice were bred with mice expressing adiponectin/Cre to selectively express human sPRR in adipocytes (adi-HsPRR). Adi-HsPRR and control littermate (CTL) male and female mice were fed HF-diet for 20 weeks (N=8-15/group). Body weight was assessed weekly and body composition monthly. Blood pressure was measured by telemetry after 15 weeks of diet. Adipose-derived human sPRR did not significantly elevate body weight or fat mass (Male: CTL.18.3±1.0g; adi-HsPRR. 17.5±0.8g. Female: CTL. 15.6±1.5g; adi-HsPRR. 11.9±1.3g; p>0.05). Systolic blood pressure (SBP) significantly increased in HF-fed male and female mice however; adipose-derived human sPRR did not further elevate SBP (24h SBP. Male: CTL. 136.0±1.7 mmHg; adi-HsPRR: 133.4±1.5mmHg; Female: CTL. 131.9±2.8 mmHg; adi-HsPRR: 130.6±3.1 mmHg; p>0.05). Surprisingly, the anti-hypertensive effect of losartan (Los) to lower blood pressure was significantly reduced in adi-HsPRR male and female mice (Male: CTL. ΔSBP: -12.1±1.5 ΔmmHg; adi-HsPRR: -7.8±0.6 ΔmmHg; Female: CTL. ΔSBP: -13.4±1.1 ΔmmHg; adi-HsPRR: -5.7±2.3 ΔmmHg; p<0.05). In 3T3-L1 cells, sPRR significantly increased phosphorylation of ERK1/2, which was not completely blunted by Los indicating that human sPRR could act as a partial agonist of AT1R or activate ERK1/2 independently of AT1R. Our data suggests that adipose-derived sPRR does not stimulate AT1R-mediated contractility, instead impairs Los efficacy.

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