Post-exercise hypotension in male spontaneously hypertensive rats: The issue of calculation method.

In spontaneously hypertensive rats, exercise can lead to a post-exercise decrease in blood pressure, named post-exercise hypotension (PEH). This can be following physical training but also after a single bout of mild to moderate exercise when measured with tail-cuff or externalized catheter methods. Our aim was to assess the PEH obtained with different calculation methods and to compare the magnitude of this effect induced by a moderate-intensity continuous exercise or a high-intensity intermittent exercise. Thirteen 16-week-old male spontaneously hypertensive rats performed two types of aerobic exercise (continuous or intermittent) on a treadmill. Arterial pressure was recorded by telemetry for 24 h which was started 3 h before physical exercise. Based on the literature, PEH was first evaluated with two different baseline values, and then with three different approaches. We observed that the identification of PEH depended on the method used to measure the rest value, and that its amplitude was also influenced by the calculation approach and the type of exercise performed. Hence, the calculation method and the amplitude of the detected PEH can significantly influence their physiological and pathophysiological inferences.

Nasogastric bridles are associated with improved tube-related outcomes in children.

OBJECTIVE: To compare tube-related outcomes in children with standard tape vs nasal bridle securement of nasogastric tubes (NGTs). STUDY DESIGN: This was a single-center, retrospective, correlational study of outcomes from the time of NGT placement until full oral feeds or durable-tube placement. Outcomes of interest included NGT dislodgments, length of stay, emergency department (ED) encounters, radiographic exposures, and adverse skin outcomes. Negative binomial regression and logistic regression were used to analyze differences between groups. RESULTS: Five hundred eighty-two children had NGTs secured traditionally (43% female; age at therapy initiation of 2.6 months [SD 8.1]), and 173 received nasal bridles (55.5% female; age at therapy initiation of 8.4 months [SD 11.8]). Children with bridled NGTs were 16.67 times less likely to experience one or more dislodgments (odds ratio [OR] = 0.06; 95% CI, 0.04-0.09); 2.5 times less likely to have one more ED visit (OR = 0.4; 95% CI, 0.19-0.82), and 4.76 times less likely to require one more radiographic exposure (OR = 0.21; 95% CI, 0.14-0.33) than unbridled children (all P values < 0.02). The mean initial hospital length of stay was 28 and 54 days in the bridled-NGT and standard-care groups, respectively (P < 0.001). Overall, 62.4% children with bridled NGTs and 77.1% children with unbridled NGTs progressed to full oral feedings and discontinued therapy (P < 0.001). Adverse skin outcomes were rare in both groups. CONCLUSION: Children with bridled NGTs experienced fewer dislodgments, hospital days, ED encounters, and radiographic exposures than unbridled NGTs. Most children in both groups progressed to full oral feedings.

Intranasal dexmedetomidine: the ideal drug for sedation in the pediatric echo lab?

BACKGROUND: Intranasal dexmedetomidine is an attractive option for procedural sedation in pediatrics due to ease of administration and its relatively short half-life. This study sought to compare the safety and efficacy of intranasal dexmedetomidine to a historical cohort of pediatric patients sedated using chloral hydrate in a pediatric echo lab. METHODS: Chart review was performed to compare patients sedated between September, 2017 and October, 2019 using chloral hydrate and intranasal dexmedetomidine. Vital signs, time to sedation, duration of sedation, need for second dose of medication, rate of failed sedation, and impact on vital signs were compared between groups. Subgroup analysis was performed for those with complex and cyanotic heart disease. RESULTS: Chloral hydrate was used in 356 patients and intranasal dexmedetomidine in 376. Patient age, complexity of heart disease, and duration of sedation were similar. Rates of failed sedation were very low and similar. Average heart rate and minimum heart rate were lower for those receiving intranasal dexmedetomidine than chloral hydrate. Impact on vital signs was similar for those with complex and cyanotic heart disease. No adverse events occurred in either group. CONCLUSIONS: Sedation with intranasal dexmedetomidine is comparable to chloral hydrate in regards to safety and efficacy for children requiring echocardiography. Consistent with the mechanism of action, patients receiving intranasal dexmedetomidine have a lower heart rate without morbidity.

Contribution of -1031T/C and -376G/A tumor necrosis factor alpha polymorphisms and haplotypes to preeclampsia risk in Tunisia (North Africa).

Preeclampsia is a gestational disorder characterized by hypertension and proteinuria. Excessive release of pro-inflammatory cytokines, particularly tumour necrosis factor-alpha, has been demonstrated to contribute to endothelial activation and poor trophoblast invasion in placental development, resulting in preeclampsia's clinical symptoms. Genetic polymorphisms of tumour necrosis factor-alpha can regulate its production and may play an important role in the pathogenesis of this disease. This study aimed to evaluate the association of five tumour necrosis factor-alpha gene promoter single nucleotide polymorphisms, or their haplotype combinations, with preeclampsia prevalence. This case-control study was conducted on 300 women with preeclampsia and 300 age-matched women with normal pregnancy from Tunisian hospitals. Genotyping of tumour necrosis factor-alpha -1031 T/C, -376 G/A, -308 G/A, -238 G/A, and +489 G/A SNPs was performed on DNA extracted from blood samples using PCR-restriction fragment-length polymorphism analysis. Statistical analysis was performed using the chi-square test. P < 0.01 were considered statistically significant to take into consideration the multiple comparisons. A significantly higher frequency of the minor allele -1031C (p < 0.001) was observed in preeclampsia cases compared to controls. Notably, the -1031C and -376A (CA) haplotype, which correlates with a higher production of TNF-α protein, had a higher incidence in women with preeclampsia (p = 0.0005). Conversely, the TG haplotype had a low frequency in preeclampsia cases compared to controls (p = 0.002) which suggests that it is associated with a reduced incidence of preeclampsia. These results suggest that tumour necrosis factor-alpha polymorphisms, in particular the -1031C/A, and the haplotype CA, contribute to an increased risk of preeclampsia in Tunisian women.

MMP-2 and MMP-9 Polymorphisms and Preeclampsia Risk in Tunisian Arabs: A Case-Control Study.

The abnormal production of matrix metalloproteinases (MMPs), especially MMP-9 and MMP-2, plays a pivotal role in hypertensive disorders of pregnancy, and as such, can influence the development of preeclampsia. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 and MMP-2 genes, which modify MMP-9 and MMP-2 expression. We investigated the association of MMP-9 polymorphism rs3918242 (-1562 C>T) and MMP-2 polymorphism rs2285053 (-735 C>T) with the risk of preeclampsia. This case-control study was conducted on 345 women with preeclampsia and 281 age-matched women with normal pregnancies from Tunisian hospitals. Genomic DNA was extracted from whole blood collected at delivery. Genotypes for -1562 C>T and -735 C>T polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An increased frequency of heterozygous MMP-9 -1562 C/T genotype carriers was observed in women with preeclampsia compared to healthy controls (p = 0.03). In contrast, the MMP-2 -735 C>T polymorphism was not significantly different regarding frequency distribution of the allele and genotype between healthy pregnant women and women with preeclampsia. Our study suggests that the MMP-9 -1562 C/T variant, associated with high MMP-9 production, could be a genetic risk factor for preeclampsia in Tunisian women.

Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters.

Potassium-coupled chloride transporters (KCCs) play crucial roles in regulating cell volume and intracellular chloride concentration. They are characteristically inhibited under isotonic conditions via phospho-regulatory sites located within the cytoplasmic termini. Decreased inhibitory phosphorylation in response to hypotonic cell swelling stimulates transport activity, and dysfunction of this regulatory process has been associated with various human diseases. Here, we present cryo-EM structures of human KCC3b and KCC1, revealing structural determinants for phospho-regulation in both N- and C-termini. We show that phospho-mimetic KCC3b is arrested in an inward-facing state in which intracellular ion access is blocked by extensive contacts with the N-terminus. In another mutant with increased isotonic transport activity, KCC1Δ19, this interdomain interaction is absent, likely due to a unique phospho-regulatory site in the KCC1 N-terminus. Furthermore, we map additional phosphorylation sites as well as a previously unknown ATP/ADP-binding pocket in the large C-terminal domain and show enhanced thermal stabilization of other CCCs by adenine nucleotides. These findings provide fundamentally new insights into the complex regulation of KCCs and may unlock innovative strategies for drug development.

Actual and Potential Impact of a Home Nasogastric Tube Feeding Program for Infants Whose Neonatal Intensive Care Unit Discharge Is Affected by Delayed Oral Feedings.

OBJECTIVE: To compare healthcare use and parent health-related quality of life (HRQL) in 3 groups of infants whose neonatal intensive care unit (NICU) discharge was delayed by oral feedings. STUDY DESIGN: This was a prospective, single-center cohort of infants in the NICU from September 2018 to March 2020. After enrollment, weekly chart review determined eligibility for home nasogastric (NG) feeds based on predetermined criteria. Actual discharge feeding decisions were at clinical discretion. At 3 months' postdischarge, we compared acute healthcare use and parental HRQL, measured by the PedsQL Family Impact Module, among infants who were NG eligible but discharged with all oral feeds, discharged with NG feeds, and discharged with gastrostomy (G) tubes. We calculated NICU days saved by home NG discharges. RESULTS: Among 180 infants, 80 were orally fed, 35 used NG, and 65 used G tubes. Compared with infants who had NG-tube feedings, infants who had G-tube feedings had more gastrointestinal or tube-related readmissions and emergency encounters (unadjusted OR 3.97, 95% CI 1.3-12.7, P = .02), and orally-fed infants showed no difference in use (unadjusted OR 0.41, 95% CI 0.1-1.7, P = .225). Multivariable adjustment did not change these comparisons. Parent HRQL at 3 months did not differ between groups. Infants discharged home with NG tubes saved 1574 NICU days. CONCLUSIONS: NICU discharge with NG feeds is associated with reduced NICU stay without increased postdischarge healthcare use or decreased parent HRQL, whereas G-tube feeding was associated with increased postdischarge healthcare use.

Reining in Nasogastric Tubes: Implementation of a Pediatric Bridle Program.

Nasogastric tubes (NG) used for enteral nutrition support of medically complex children (MCC) are often inadvertently removed, risking frequent replacements. Bridles have been shown to provide a safe securement method for NGs in adult patients, but are not widely used in pediatrics. Furthermore, nutritional management of MCC is often fragmented. We established a pediatric NG bridle program to bridge the gap amongst disciplines and improve patient outcomes. In January 2018, a multidisciplinary work group involving nurses, physicians, clinical dietitians, advanced practice providers, and speech-language pathologists was established to develop criteria for patient referral and policies, procedures, and order sets for nutritional management of MCC children with bridled NG tubes. Formal teaching sessions engaged clinicians and administrators to participate in building a successful program. Relevant outcomes of interest are tracked continuously for process performance improvement measures and are reviewed quarterly by the core work group. Patient enrollment began in May 2018 and to date, 244 patients have been enrolled. Adhering to strict enrollment criteria, competency modules and review of patient status provided a solid core for the program and process review. Successful implementation of an NG Bridle program was achieved. Outcomes of interest continue to be monitored for process improvement. Balancing measures are also being tracked for potential downstream effects.

A Longitudinal Pilot Study on Cognition and Cerebral Hemodynamics in a Mouse Model of Preeclampsia Superimposed on Hypertension: Looking at Mothers and Their Offspring.

Preeclampsia is a common hypertensive disorder in pregnant women and whose causes and consequences have focused primarily on cardiovascular outcomes on the mother and offspring, often without taking into consideration the possible effects on the brain. One possible cause of preeclampsia has been attributed to alterations in the renin-angiotensin system, which has also been linked to cognitive decline. In this pilot study, we use a transgenic mouse model that chronically overexpresses human angiotensinogen and renin (R+A+ mice) that displayed characteristics of preeclampsia such as proteinuria during gestation. Offspring of these mothers as well as from control mothers were also examined. We were primarily interested in detecting whether cognitive deficits were present in the mothers and offspring in the long term and used a spatial learning and memory task as well as an object recognition task at three timepoints: 3, 8, and 12 months post-partum or post-natal, while measuring blood pressure and performing urine analysis after each timepoint. While we did not find significant deficits in preeclamptic mothers at the later timepoints, we did observe negative consequences in the pups of R+A+ mice that coincided with hemodynamic alterations whereby pups had higher whisker-evoked oxygenated hemoglobin levels and increased cerebral blood flow responses compared to control pups. Our study provides validation of this preeclampsia mouse model for future studies to decipher the underlying mechanisms of long-term cognitive deficits found in offspring.

Increased physical activity is correlated with improved pregnancy outcomes in women with preeclampsia: A retrospective study.

OBJECTIVES: Several studies have focused on the benefits of physical activity to prevent and treat preeclampsia, given that preeclampsia and cardiovascular disease share several risk factors. However, none of these studies have been conducted in Africa. Moreover, it has been demonstrated that exercise training has preventive effects on the development of preeclampsia in mouse models. Therefore, we evaluated the association between the practice of physical activity and the development of this pathology in a Tunisian cohort. STUDY DESIGN: Sixty-one healthy pregnant Tunisian women and 45 women with preeclampsia were recruited and completed the Pregnancy Physical Activity Questionnaire to determine their level and type of physical activity during the entire pregnancy. MAIN OUTCOME MEASURE: Continuous variables were compared using the Mann-Whitney U test, while categorical variables were compared using the Chi-square test. The correlation between preeclampsia features and energy expenditure were assessed using the Pearson's correlation test. RESULTS: Energy expenditure analysis revealed that women with preeclampsia engaged in more sedentary activities than controls, while controls practiced more physical activities. Interestingly, we found a positive correlation between the total amount of energy spent and the duration of pregnancy in controls and women with preeclampsia. CONCLUSIONS: Increasing physical activity is correlated with increasing pregnancy duration which is an index of maternal and fetal health. The practice of physical activities during pregnancy is associated with a healthier pregnancy, while sedentary activities is associated with the development of preeclampsia.

Selective Use of Inpatient Interstage Management After Norwood Procedure.

BACKGROUND: We report our intermediate-term results after Norwood procedure, including use of an interstage inpatient management strategy for high-risk patients, and seek to create a predictive model for probability of discharge. METHODS: A single-site retrospective review was conducted for all patients undergoing Norwood procedure from 2006 to 2016 (N = 177). We compared those discharged home with those who either remained hospitalized until Glenn procedure or died before Norwood procedure discharge. Multivariable logistic regression was used to develop a predictive model for discharge. RESULTS: During the study period, 120 (68%) patients were discharged home, 45 (25%) remained hospitalized, and 12 (7%) died before Glenn procedure (median age: 71 days). Interstage survival for those discharged after Norwood procedure was 100%. Longitudinal survival for the cohort was 86%, 81%, and 77% at 1, 5, and 10 years, resepectively. Ten-year survival was significantly greater for the discharged group compared with the interstage inpatients (86% vs 56%, P < .001). A reduced predictive model of discharge included lower gestational age (odds ratio [OR]: 0.95), lower median income for ZIP code (OR: 0.4), lower birth-weight-for-age z-score (OR: 0.56), longer cardiopulmonary bypass time (OR: 0.45), and Blalock-Taussig shunt (OR: 0.32). CONCLUSIONS: Survival up to 10 years after Norwood procedure is good using a strategy of inpatient care for a subset of high-risk patients to mitigate home interstage mortality. A probabilistic model used after Norwood procedure was able to predict interstage discharge with good accuracy, but will require external validation to ensure generalizability. Further work is also needed to determine optimal palliative pathways for the high-risk patients because of the notable attrition beyond successful bidirectional Glenn procedure.

Echocardiography vs cardiac magnetic resonance imaging assessment of the systemic right ventricle for patients with d-transposition of the great arteries status post atrial switch.

OBJECTIVE: Patients with Dextro-transposition of the great arteries status post atrial switch (dTGA s/p atrial switch) are "at-risk" for systemic right ventricular (RV) dysfunction. Due to complex RV geometry, echocardiography (Echo) does not allow accurate determination of ejection fraction (EF), but cardiac magnetic resonance imaging (CMR) allows quantitative right ventricular assessment. Measures of ventricular deformation may be precursors to global ventricular dysfunction. The primary aim of this study was to characterize imaging and clinical findings for adult patients with dTGA s/p atrial switch. DESIGN: This was a retrospective cohort study of patients with dTGA s/p atrial switch operation (February 1966 to August 1988) with CMR performed at Children's Hospital of Wisconsin (from September 2005 to May 2015). Eligible patients had clinic visit, Echo, and exercise stress test within 1 year of CMR. RESULTS: This study enrolled twenty-seven patients (16 males, 11 females) with dTGA s/p atrial switch (18 with Mustard operation and 9 with Senning operation; median age 30 years; 74% New York Heart Association class 1 and 26% class 2). Seventy-four percentage had normal RV systolic function (RV EF >45% by CMR). No correlation was observed between Echo strain data and clinical status (EF, exercise endurance, VO2 max, or New York Heart Association class). Cardiac magnetic resonance imaging RV global circumferential strain GCS and RV EF had moderate negative correlation (r = -0.65, P < .001). Global circumferential strain was significantly different for those with RV EF above and below 45%, while global peak longitudinal strain (GLS) was not. Patients had reduced CMR myocardial strain values compared with healthy controls. CONCLUSIONS: Reduced RV CMR GCS (for those with RV EF <45%) suggests that CMR evaluation may enhance early detection of detrimental changes in the systemic RV myocardium.

Implementation of Quality-of-Life Assessment Increases Referrals for Intervention in Patients with Tetralogy of Fallot.

Mortality from surgical repair of tetralogy of Fallot (TOF) has decreased dramatically over the last several decades. Despite excellent surgical outcomes, studies reveal that patients with TOF continue to have decreased physical functioning, academic difficulties, and psychosocial impairments. We hypothesized that administering a validated quality-of-life assessment to patients with TOF during routine cardiology follow-up visits would help identify deficits and increase referrals to appropriate interventional programs. Between May 2017 and November 2018, TOF patients (5-20 years) and/or their families completed a standardized quality-of-life assessment (PedsQL 4.0) during cardiology clinic visits. Providers were encouraged to refer patients with abnormal PedsQL 4.0 scores to appropriate services including cardiovascular rehabilitation, psychological evaluation, neurodevelopmental testing, and school intervention. Referrals for the intervention group were compared to those of a control group using χ2 analysis. The PedsQL 4.0 was completed by 79 patients at 90 clinic visits. At least one abnormal PedsQL 4.0 score was identified in 58% (52/90) of patient encounters, and of those 52 encounters, 38% (20/52) received at least one referral for intervention. The most commonly placed referrals were for neurodevelopmental testing (16) and school intervention (11). When comparing the number of referrals from the intervention group to those of the control group, referrals to all intervention services were statistically significant (p < 0.05). Our quality improvement initiative successfully utilized a quality-of-life assessment to detect deficits and subsequently increased the number of referrals to intervention services. Future studies will address barriers that prevent completion of the PedsQL and assess how interventions impact quality-of-life scores.

Telerehabilitation with live-feed biomedical sensor signals for patients with heart failure: a pilot study.

BACKGROUND: Integrating biomedical sensors to a telerehabilitation platform allowed clinicians to receive real-time transmissions of the electrocardiogram (ECG) signal, oxygen saturation, and heart rate during an exercise program. These clinical data could be helpful to adjust and personalize the intensity of exercises to each patient's condition. The purpose of this study was to evaluate the feasibility and usefulness of biomedical sensors in telerehabilitation in patients with heart failure (HF). METHODS: Four participants with HF (mean age 66 years) followed the 12-week cardiac program using telerehabilitation, including sensors to monitor real-time vital signs during sessions. The exercise program included cardiovascular, strengthening and flexibility exercises. Participants were evaluated before the intervention and one month after the end of the program. Functional capacity was measured with Cardiopulmonary Exercise Testing (CPX), the 6-minute walk test (6MWT), and the sit to stand test (STST). Quality of life was objectified using the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: Our main objective demonstrated that real-time biomedical sensors can be safely used by clinicians during a telerehabilitation session. Most participants showed a tendency to improve their physical capacities such as walking distance and lower limb muscular strength. As a main outcome of cardiac rehabilitation (CR), quality of life seems to improve after the 12-week intervention. CONCLUSIONS: This study proved the feasibility of using telerehabilitation with real-time biomedical sensors as an alternative or a complement to the conventional CR program. Use of sensors allowed a safe environment for the patient and an adequate and personalized exercise prescription. Limitation in one-to-one supervision must be challenged in future clinical trials to demonstrate that telerehabilitation could be efficient for cardiac patients requiring more individual supervision than group sessions in a gymnasium.

Mouse Adipose Tissue Collection and Processing for RNA Analysis.

Compared to other tissues, white adipose tissue has a considerably less RNA and protein content for downstream applications such as real-time PCR and Western Blot, since it mostly contains lipids. RNA isolation from adipose tissue samples is also challenging as extra steps are required to avoid these lipids. Here, we present a procedure to collect three anatomically different white adipose tissues from mice, to process these samples and perform RNA isolation. We further describe the synthesis of cDNA and gene expression experiments using real-time PCR. The hereby described protocol allows the reduction of contamination from the animal's hair and blood on fat pads as well as cross-contamination between different fat pads during tissue collection. It has also been optimized to ensure adequate quantity and quality of the RNA extracted. This protocol can be widely applied to any mouse model where adipose tissue samples are required for routine experiments such as real-time PCR but is not intended for isolation from primary adipocytes cell culture.

Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight.

OBJECTIVE: We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. METHODS: An adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. RESULTS: KO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR. CONCLUSIONS: (P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

Reduced blood pressure after smooth muscle EFNB2 deletion and the potential association of EFNB2 mutation with human hypertension risk.

Ephrin B2 (EFNB2) is a ligand for erythropoietin-producing hepatocellular kinases (EPH), the largest family of receptor tyrosine kinases. It has critical functions in many biological systems, but is not known to regulate blood pressure. We generated mice with a smooth muscle cell (SMC)-specific deletion of EFNB2 and investigated its roles in blood pressure regulation and vascular SMC (VSMC) contractility. Male Efnb2 knockout (KO) mice presented reduced blood pressure, whereas female KO mice had no such reduction. Both forward signaling from EFNB2 to EPHs and reverse signaling from EPHs to EFNB2 were involved in regulating VSMC contractility, with EPHB4 serving as a critical molecule for forward signaling, based on crosslinking studies. We also found that a region from aa 313 to aa 331 in the intracellular tail of EFNB2 was essential for reverse signaling regulating VSMC contractility, based on deletion mutation studies. In a human genetic study, we identified five SNPs in the 3' region of the EFNB2 gene, which were in linkage disequilibrium and were significantly associated with hypertension for male but not female subjects, consistent with our findings in mice. The coding (minor) alleles of these five SNPs were protective in males. We have thus discovered a previously unknown blood pressure-lowering mechanism mediated by EFNB2 and identified EFNB2 as a gene associated with hypertension risk in humans.

Prorenin/renin receptor blockade promotes a healthy fat distribution in obese mice.

OBJECTIVE: Administration of the handle region peptide (HRP), a (pro)renin receptor blocker, decreases body weight gain and visceral adipose tissue (VAT) in high-fat/high-carbohydrate (HF/HC) diet-fed mice. The objective of this study was to elucidate potential mechanisms implicated in these observations. METHODS: Mice were given a normal or a HF/HC diet along with saline or HRP for 10 weeks. RESULTS: In HF/HC-fed mice, HRP increased the expression of several enzymes implicated in lipogenesis and lipolysis in subcutaneous fat (SCF) while the expression of the enzyme implicated in the last step of lipogenesis decreased in VAT. A reduction was also observed in circulating free fatty acids in these animals which was accompanied by normalized adipocyte size in VAT and increased adipocyte size in SCF. ''Beiging'' is the evolution of a white adipose tissue toward a brown-like phenotype characterized by an increased mitochondrial density and small lipid droplets. HRP increased the expression of' "beiging" markers in SCF of HF/HC diet-fed mice. CONCLUSIONS: HRP treatment may favor healthy fat storage in SCF by activating a triglyceride/free fatty acid cycling and "beiging," which could explain the body weight and fat mass reduction.

Oxytocin decreases diurnal and nocturnal arterial blood pressure in the conscious unrestrained spontaneously hypertensive rat.

In this study, we assessed the effects of oxytocin (OT) on mean arterial blood pressure (MAP), heart rate (HR), and locomotor activity (LA) in male spontaneous hypertensive rats (SHR) and Sprague-Dawley (SDR) controls using telemetry. OT was given by intravenous injections of 0.1, 0.2 or 0.4mg/kg to assess short term acute effects or by daily subcutaneous injections of 0.5 or 1.0mg/kg for 5 days. Compared to the saline infusion, (i) intravenous OT, regardless of concentration, increased MAP in SHR and SDR, (ii) HR increased, but was periodically lower in both strains with 0.2 or 0.4mg/kg, and (iii) no effects of OT on LA were observed. Subcutaneous injections demonstrated that (i) 1.0mg/kg for 5days lowered diurnal MAP and HR in SDR and SHR, persisting for 6 days, (ii) 1.0mg/kg decreased nocturnal HR in SDR, (iii) 0.5 and 1.0mg/kg decreased MAP with minor effects on HR in the SHR, and lastly (iv) OT decreased LA mainly during the diurnal cycle in both strains. Our main results show that OT induces significant beneficial effects on cardiovascular function over several diurnal and nocturnal cycles in the SHR, with the most prominent effect being a robust decrease in MAP.