Comparative assessment of CacyBP/SIP, ß-catenin and cannabinoid receptors in the adrenals of hypertensive rats.

Taking into account homeostatic disorders resulting from arterial hypertension and the key importance of CacyBP/SIP, ß-catenin and endocannabinoids in the functioning of many organs, it was decided to assess the presence and distribution of CacyBP/SIP, ß-catenin, CB1 and CB2 in the adrenal glands of hypertensive rats of various aetiology. The study was conducted on the adrenal glands of rats with spontaneous and renovascular hypertension. The expression of CacyBP/SIP, ß-catenin, CB1 and CB2 was detected by immunohistochemistry and real-time PCR method. The results of the present study revealed both lower gene expression and immunoreactivity of CacyBP/SIP in the adrenal glands of all hypertensive groups compared to the normotensive rats. This study demonstrated a reduction in the immunoreactivity and expression of the ß-catenin, CB1 and CB2 genes in the adrenals of 2K1C rats. While in SHR, the reaction showing ß-catenin and CB1 was very weak or negative, and the expression of CB2 in the adrenal glands of these rats increased. The results of this study show, for the first time, marked differences in the expression of CacyBP/SIP, ß-catenin and CB1 and CB2 cannabinoid receptors in the adrenal glands of rats with primary (SHR) and secondary hypertension (2K1C).

Spontaneously hypertensive rats vs. Wistar Kyoto and Wistar rats: An assessment of anxiety, motor activity, memory performance, and seizure susceptibility.

Spontaneously hypertensive rats (SHRs) are widely accepted for modeling essential hypertension and Attention deficit hyperactivity disorder (ADHD). However, data concerning central nervous system changes associated with behavioral responses of this strain and usage of Wistar Kyoto (WKY) rats as controls are confounding. The objective of the present study was to assess the impact of anxiety and motor activity on the cognitive responses of SHRs compared to Wistar and WKY rats. In addition, the role of brain-derived neurotrophic factor (BDNF) in the hippocampus on cognitive behavior and seizure susceptibility in the three strains was evaluated. In Experiment#1, SHR demonstrated impulsive responses in the novelty suppression feeding test accompanied by impaired spatial working and associative memory in the Y maze and object recognition test compared with the Wistar rat but not WKY rats. In addition, the WKY rats exhibited diminished activity compared to Wistar rats in an actimeter. In Experiment#2, the seizure susceptibility was assessed by 3-min electroencephalographic (EEG) recording after two consecutive injections of pentylenetetrazol (PTZ) (20+40 mg/kg). The WKY rats were more vulnerable to rhythmic metrazol activity (RMA) than the Wistar rats. In contrast, Wistar rats were more prone to generalized tonic-clonic seizures (GTCS) than WKY rats and SHRs. Control SHR had lower BDNF expression in the hippocampus compared to Wistar rats. However, while the BDNF levels were elevated in the Wistar and WKY rats after PTZ injection, no change in this signaling molecule was observed in the SHR in the seizure condition. The results suggest Wistar rats as a more appropriate control of SHR than WKY rats for studying memory responses mediated by BDNF in the hippocampus. The higher vulnerability to seizures in Wistar and WKY rats compared to SHR might be linked to PTZ-induced decreased expression of BDNF in the hippocampus.

In vivo assessment of hypertensive nephrosclerosis using ultrasound localization microscopy.

PURPOSE: As a typical chronic kidney disease (CKD), hypertensive nephrosclerosis (HN) is a common syndrome of hypertension, characterized by chronic kidney microvascular damage. Early diagnosis of microvascular damage using conventional ultrasound imaging encounters challenges in sensitivity and specificity owing to the inherent diffraction limit. Ultrasound localization microscopy (ULM) has been developed to obtain microvasculature and microvascular hemodynamics within the kidney, and would be a promising tool for the early diagnosis of CKD. METHODS: In this study, the advantage of quantitative indexes obtained by using ULM (mean arterial blood flow speeds of different segments of interlobular arteries) over indexes obtained using conventional clinical serum (ß2-microglobulin, serum urea nitrogen, and creatinine) and urine (24-h urine volume and urine protein) tests and ultrasound Doppler imaging (peak systolic velocity [PSV], end-diastolic velocity [EDV], and resistance index [RI]) and contrast-enhanced ultrasound imaging (CEUS; rise time [RT], peak intensity [IMAX], mean transit time [mTT], and area under the time-intensity curve [AUC]) for early diagnosis of HN were investigated. Examinations were carried out on six spontaneously hypertensive rats (SHR) and five normal Wistar-Kyoto (WKY) rats at the age of 10 weeks. RESULTS: The experimental results show that the indicators derived from conventional clinical inspections (serum and urine tests) and ultrasound imaging (PSV, EDV, RI, RT, IMAX, mTT, and AUC) do not show significant difference between hypertensive and healthy rats (p > 0.05), while the TTP of the SHR group (28.52 ± 5.52 s) derived from CEUS is significantly higher than that of the WKY group (18.68 ± 7.32 s; p < 0.05). The mean blood flow speed in interlobular artery of SHR (12.47 ± 1.06 mm/s) derived from ULM is significantly higher than that of WKY rats (10.13 ± 1.17 mm/s; p < 0.01). CONCLUSION: The advantages of ULM over conventional clinical inspections and ultrasound imaging methods for early diagnosis of HN were validated. The quantitative results show that ULM can effectively diagnose HN at the early stage by detecting the blood flow speed changes of interlobular arteries. ULM may promise a reliable technique for early diagnosis of HN in the future.

An assessment of executive function in two different rat models of attention-deficit hyperactivity disorder: Spontaneously hypertensive versus Lphn3 knockout rats.

Attention-deficit/hyperactivity disorder (ADHD) a common neurodevelopmental disorder of childhood and often comorbid with other externalizing disorders (EDs). There is evidence that externalizing behaviors share a common genetic etiology. Recently, a genome-wide, multigenerational sample linked variants in the Lphn3 gene to ADHD and other externalizing behaviors. Likewise, limited research in animal models has provided converging evidence that Lphn3 plays a role in EDs. This study examined the impact of Lphn3 deletion (i.e., Lphn3-/- ) in rats on measures of behavioral control associated with externalizing behavior. Impulsivity was assessed for 30 days via a differential reinforcement of low rates (DRL) task and working memory evaluated for 25 days using a delayed spatial alternation (DSA) task. Data from both tasks were averaged into 5-day testing blocks. We analyzed overall performance, as well as response patterns in just the first and last blocks to assess acquisition and steady-state performance, respectively. "Positive control" measures on the same tasks were measured in an accepted animal model of ADHD-the spontaneously hypertensive rat (SHR). Compared with wildtype controls, Lphn3-/- rats exhibited deficits on both the DRL and DSA tasks, indicative of deficits in impulsive action and working memory, respectively. These deficits were less severe than those in the SHRs, who were profoundly impaired on both tasks compared with their control strain, Wistar-Kyoto rats. The results provide evidence supporting a role for Lphn3 in modulating inhibitory control and working memory, and suggest additional research evaluating the role of Lphn3 in the manifestation of EDs more broadly is warranted.

Categorizing SHR and WKY rats by chi2 algorithm and decision tree.

Classifying mental disorder is a big issue in psychology in recent years. This article focuses on offering a relation between decision tree and encoding of fMRI that can simplify the analysis of different mental disorders and has a high ROC over 0.9. Here we encode fMRI information to the power-law distribution with integer elements by the graph theory in which the network is characterized by degrees that measure the number of effective links exceeding the threshold of Pearson correlation among voxels. When the degrees are ranked from low to high, the network equation can be fit by the power-law distribution. Here we use the mentally disordered SHR and WKY rats as samples and employ decision tree from chi2 algorithm to classify different states of mental disorder. This method not only provides the decision tree and encoding, but also enables the construction of a transformation matrix that is capable of connecting different metal disorders. Although the latter attempt is still in its fancy, it may have a contribution to unraveling the mystery of psychological processes.

Isolation and Characterization of Angiotensin Converting Enzyme Inhibitory Peptides from Peach Seed Hydrolysates: In Vivo Assessment of Antihypertensive Activity.

A peptide fraction with molecular masses below 3 kDa (PSH-3 kDa) from a peach seed hydrolysate demonstrated high angiotensin converting enzyme (ACE) inhibitory activity (concentration to inhibit 50% ACE (IC50) = 16.4 µg/mL) in our previous work. This work proposes a further study of this highly active fraction. RP-HPLC enabled two fractions (F3 and F4) with high inhibitory activity (IC50 = 2.0 ± 0.5 and 1.2 ± 0.2 µg/mL, respectively) to be isolated. Peptide analysis by LC-Q-TOF-MS/MS using reverse-phase and hydrophilic interaction chromatography enabled 33 peptides within both fractions to be identified. Among them, peptide isoleucine-tyrosine-serine-proline-histidine (IYSPH) showed the highest capacity. The lack of cytotoxicity of peptides was demonstrated in three different cell lines (HeLa, HT-29, and HK-2). Oral administration of PSH-3 kDa fraction or peptide IYSPH caused a significant systolic blood pressure reduction (-30 mmHg) on spontaneously hypertensive rats after 3-6 h treatment.

Dietary Sparassis crispa Reduces Body Fat Mass and Hepatic Lipid Levels by Enhancing Energy Expenditure and Suppressing Lipogenesis in Rats.

Accumulation of abdominal fat triggers metabolic syndrome, which is a cluster of metabolic abnormalities, such as dyslipidemia, glucose intolerance, insulin resistance or hyperinsulinemia, and hypertension, that leads to the development of diabetes and cardiovascular disease. Mushrooms have been used as a foodstuff and folk medicine worldwide. Among these mushrooms, Sparassis crispa (SC) is a relatively newly cultivated edible and medicinal mushroom, which has been reported to have anti-diabetic and anti-hypertensive properties. However, little is known about the anti-obesity and anti-hyperlipidemic properties of SC. In the present study, we investigated the effects of dietary SC on lipid metabolism and energy expenditure in Sprague-Dawley rats with diet-induced obesity and diabetes, and conducted respiratory gas analysis to determine how energy metabolism is altered by SC. After feeding periods of 3 and 7 weeks, dietary SC had significantly reduced hepatic triacylglycerol and cholesterol contents in a dose-dependent manner. These changes were attributable to suppression of fatty acid and cholesterol synthesis in the liver and increased insulin sensitivity in the body. In addition, after a feeding period of 6 weeks, dietary SC significantly increased energy expenditure through carbohydrate oxidation, reducing abdominal fat mass after 7 weeks. In conclusion, our results indicate that in addition to the previously reported anti-diabetic and anti-hypertensive activities, dietary SC exhibits anti-obesity and anti-hyperlipidemic activities that help protect against metabolic syndrome.

Physical Exercise and Regulation of Intracellular Calcium in Cardiomyocytes of Hypertensive Rats / Exercício Físico e Regulação de Cálcio Intracelular em Cardiomiócitos de Ratos Hipertensos

Abstract Background: Regulation of intracellular calcium (Ca2+) in cardiomyocytes is altered by hypertension; and aerobic exercise brings benefits to hypertensive individuals. Objective: To verify the effects of aerobic exercise training on contractility and intracellular calcium (Ca2+) transients of cardiomyocytes and on the expression of microRNA 214 (miR-214) in the left ventricle of spontaneously hypertensive rats (SHR). Methods: SHR and normotensive Wistar rats of 16 weeks were divided into 4 groups -sedentary hypertensive (SH); trained hypertensive (TH); sedentary normotensive (SN); and trained normotensive (TN). Animals of the TH and TN groups were subjected to treadmill running program, 5 days/week, 1 hour/day at 60-70% of maximum running velocity for 8 weeks. We adopted a p ≤ 0.05 as significance level for all comparisons. Results: Exercise training reduced systolic arterial pressure in hypertensive rats. In normotensive rats, exercise training reduced the time to 50% cell relaxation and the time to peak contraction and increased the time to 50% decay of the intracellular Ca2+ transients. In SHR, exercise increased the amplitude and reduced the time to 50% decay of Ca2+ transients. Exercise training increased the expression of miR-214 in hypertensive rats only. Conclusion: The aerobic training applied in this study increased the availability of intracellular Ca2+ and accelerated the sequestration of these ions in left ventricular myocytes of hypertensive rats, despite increased expression of miR-214 and maintenance of cell contractility.

Resumo Fundamento: A regulação intracelular de cálcio (Ca2+) em cardiomiócitos é alterada pela hipertensão, e o exercício físico aeróbico traz benefícios para hipertensos. Objetivo: Verificar os efeitos do treinamento físico aeróbico sobre a contratilidade e a concentração intracelular de Ca2+ transitória em miócitos e a expressão do microRNA 214 no ventrículo esquerdo (VE) de ratos espontaneamente hipertensos (SHR). Métodos: SHR e ratos Wistar normotensos com 16 semanas de idade foram divididos em 4 grupos de 13 animais cada: hipertenso sedentário (HS); hipertenso treinado (HT); normotenso sedentário (NS); normotenso treinado (NT). Os animais dos grupos HT e NT foram submetidos a um programa de treinamento progressivo de corrida em esteira, 5 dias/semana, 1 hora/dia, em intensidade de 60-70% da velocidade máxima de corrida, durante 8 semanas. Adotou-se p ≤ 0,05 como nível de significância em todas as comparações. Resultados: O treinamento físico reduziu a pressão arterial sistólica nos animais hipertensos. Nos animais normotensos, o treinamento físico reduziu o tempo para 50% de relaxamento celular e o tempo para o pico de contração celular, mas aumentou o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória. Nos animais SHR, o treinamento físico aumentou a amplitude e reduziu o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória, sem alterar a contratilidade celular. O treinamento físico aumentou a expressão do miR-214 apenas nos animais hipertensos. Conclusão: O treinamento aeróbico utilizado aumenta a disponibilidade e acelera o sequestro de Ca2+ intracelular em miócitos do VE de ratos hipertensos, apesar do aumento da expressão de miR-214 e da manutenção da contratilidade celular.

Influence of pre-existing hypertension on neuroendocrine and cardiovascular changes evoked by chronic stress in female rats.

This study investigated neuroendocrine, autonomic, and cardiovascular changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in 60-days-old female normotensive Wistar rats and female spontaneously hypertensive rats (SHR). Both strains of rats were exposed for 10 consecutive days to either the homotypic stressor repeated restraint stress (RRS) or the heterotypic stressor chronic unpredictable stress (CUS). As expected, SHR had higher baseline blood pressure values and impaired baroreflex activity in relation to normotensive animals. Besides, SHR presented higher plasma corticosterone levels and decreased thymus weight. Both RRS and CUS increased baseline plasma corticosterone concentration and decreased body weight gain in both normotensive and SHR rats. In addition, both stress protocols caused hypertrophy of adrenal glands in normotensive rats. Regarding the cardiovascular effects, RRS increased basal heart rate in both rat strains, which was mediated by an increase in sympathetic tone to the heart. Besides, RRS increased baroreflex-mediated tachycardia in SHR animals, while CUS increased cardiac parasympathetic activity and pacemaker activity in normotensive rats. Taken together, these results indicate a stress type-specific effect, as identified by a vulnerability of both strains to the deleterious cardiovascular effects evoked by the homotypic stressor and a resilience to the impact of the heterotypic stressor. Vulnerability of hypertensive rats was evidenced by the absence of CUS-evoked adaptive cardiovascular responses and an increase of baroreflex tachycardia in SHR animals subjected to RRS. The somatic and HPA axis changes were overall independent of the chronic stress regimen and pre-existing hypertension.

A schizophrenia-like behavioral trait in the SHR model: Applying confirmatory factor analysis as a new statistical tool.

Questionnaires that assess symptoms of schizophrenia patients undergo strict statistical validation, often using confirmatory factor analysis (CFA). CFA allows testing the existence of a trait that both collectively explains the symptoms and gathers the information in a single general index. In rodents, some behaviors are used to model psychiatric symptoms, but no single test or paradigm adequately captures the disorder's phenotype in toto. This work investigated the existence of a behavioral trait in the SHR strain underlying five behavioral tasks used in schizophrenia animal studies and altered in this strain: locomotor activity, rearing behavior, social interaction, prepulse inhibition of startle and contextual fear conditioning. The analysis was conducted on a sample of Wistar (n = 290) and Spontaneously Hypertensive Rats (SHRs, n = 290). CFA showed the existence of a continuous trait in both strains, and higher values among SHRs. This work is the first to demonstrate the existence of a schizophrenia-like trait in an animal model. We suggest that using CFA to evaluate behavioral parameters in animals might facilitate the pre-clinical investigation of psychiatric disorders, diminishing the gap between animal and human studies.

Genetics of hypertension: an assessment of progress in the spontaneously hypertensive rat.

The application of gene mapping methods to uncover the genetic basis of hypertension in the inbred spontaneously hypertensive rat (SHR) began over 25 yr ago. This animal provides a useful model of genetic high blood pressure, and some of its features are described. In particular, it appears to be a polygenic model of disease, and polygenes participate in human hypertension genetic risk. The SHR hypertension alleles were fixed rapidly by selective breeding in just a few generations and so are presumably common genetic variants present in the outbred Wistar strain from which SHR was created. This review provides a background to the origins and genesis of this rat line. It considers its usefulness as a model organism for a common cardiovascular disease. The progress and obstacles facing mapping are considered in depth, as are the emergence and application of other genome-wide genetic discovery approaches that have been applied to investigate this model. Candidate genes, their identification, and the evidence to support their potential role in blood pressure elevation are considered. The review assesses the progress that has arisen from this work has been limited. Consideration is given to some of the factors that have impeded progress, and prospects for advancing understanding of the genetic basis of hypertension in this model are discussed.

Weighted averaging in spectroscopic studies improves statistical power.

PURPOSE: In vivo MRS is often characterized by a spectral signal-to-noise ratio (SNR) that varies highly between experiments. A common design for spectroscopic studies is to compare the ratio of two spectral peak amplitudes between groups, e.g. individual PCr/γ-ATP ratios in 31 P-MRS. The uncertainty on this ratio is often neglected. We wished to explore this assumption. THEORY: The canonical theory for the propagation of uncertainty on the ratio of two spectral peaks and its incorporation in the Frequentist hypothesis testing framework by weighted averaging is presented. METHODS: Two retrospective re-analyses of studies comparing spectral peak ratios and one prospective simulation were performed using both the weighted and unweighted methods. RESULTS: It was found that propagating uncertainty correctly improved statistical power in all cases considered, which could be used to reduce the number of subjects required to perform an MR study. CONCLUSION: The variability of in vivo spectroscopy data is often accounted for by requiring it to meet an SNR threshold. A theoretically sound propagation of the variable uncertainty caused by quantifying spectra of differing SNR is therefore likely to improve the power of in vivo spectroscopy studies. Magn Reson Med 78:2082-2094, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

In Vitro and In Vivo Assessment of Angiotensin-Converting Enzyme (ACE) Inhibitory Activity of Fermented Soybean Milk by Lactobacillus casei Strains.

Angiotensin-converting enzyme (ACE) inhibitory activity of fermented soybean milk (FSM) by Lactobacillus casei strains in vitro was investigated in this study. Effects of fermented soybean milk administration by gavage on systolic blood pressure and diastolic blood pressure was also evaluated in spontaneously hypertensive rats (SHR) rats and Wistar-Kyoto (WKY) rats. Results showed that, CICC 20280 and CICC 23184 FSM showed high ACE inhibitory activity in vitro test and ACE inhibitory activity of CICC 23184 FSM was higher than CICC 20280 FSM. The bioactive substances of FSM were peptide and γ-aminobutyric acid (GABA). Their contents in CICC 20280 FSM and CICC 23184 FSM were 3.97 ± 0.67 mg/ml (peptide), 1.71 ± 0.36 mg/ml (GABA) and 5.17 ± 0.22 mg/ml (peptide), 1.57 ± 0.21 mg/ml (GABA), respectively. Moreover, CICC 20280 and CICC 23184 FSM administration by gavage could effectively lower the blood pressure of SHR to a normal level, while there was no effect on blood pressure of WKY rats. This result indicated that the bioactive substances could play an antihypertensive role when the blood pressure was not within the normal levels (high levels).

Assessment of cardiac autonomic tone in conscious rats.

Cardiac autonomic tone can be assessed either by estimating separately vagal and sympathetic tones or by evaluating the net effect of their interaction, the so-called sympathovagal balance (SVB). To compare the most commonly used methods in rats, telemetric recordings of the electrocardiogram were performed in normotensive WKY rats, and in groups of spontaneously hypertensive (SHR) rats that were either untreated or chronically treated with the cholinesterase inhibitor, pyridostigmine, to enhance vagal tone. Cardiac autonomic blockers were administered alone and in combination, so that heart rate (HR) could be measured (1) under resting conditions, (2) with either autonomic branch blocked, and (3) with both branches blocked (which provided intrinsic HR, iHR). SVB was assessed as the ratio of resting HR to iHR. This calculation pointed to a sympathetic predominance in untreated SHRs and even more so in WKY rats, and to a marked vagal predominance in pyridostigmine-treated SHRs. By contrast, the ratio between low and high frequency components (LF/HF) of RR interval spectra did not significantly differ between the groups. Each autonomic tone was quantified as the HR change induced by its selective blocker or as the difference between iHR and HR after blockade of its counterpart. Both pharmacological methods indicated vagal enhancement in treated SHRs, but provided opposite results in terms of vagal vs. sympathetic predominance. These data seriously question the use of the LF/HF ratio as an index of SVB, and the possibility to reliably estimate vagal and sympathetic tones separately through current pharmacological approaches in conscious rats.

Regional distribution of selective neuronal loss and microglial activation across the MCA territory after transient focal ischemia: quantitative versus semiquantitative systematic immunohistochemical assessment.

Histopathologic assessment in transient middle cerebral artery occlusion (MCAo) rodent models generally lacks comprehensiveness and exposes to interobserver bias. Here we compared a novel quantitative assessment of regional infarction, selective neuronal loss (SNL) and microglial activation (MA) across the MCA territory to a previously published semiquantitative visual protocol. NeuN and OX42 immunohistochemistry was applied after either 15 or 45 minutes distal MCAo to maximize SNL and infarction, respectively. Survival times varied from 28 to 60 days to cover potential biases such as delayed tissue shrinkage. Damage was assessed using a template of 44 cytoarchitectonic regions of interest (ROIs) mapped onto a subset of digitized coronal sections spanning the MCA territory. For each ROI were obtained a semiquantitative visually determined index of histopathologic changes (method 1), and lpsilateral/contralesional ratios of remaining neurons and activated microglia cell counts (method 2). There was excellent agreement between the two methods for 28-day survival for both MCAo durations, whereas method 2 more sensitively detected subtle SNL and MA at 45 days and 60 days after 15-minute MCAo. Thus the visual method is accurate for usual degrees of ischemic damage, but absolute cell quantification is superior to detect subtle changes and should therefore be preferred in brief MCAo models, although requires optimal staining quality.

In vivo assessment of arterial stiffness in the isoflurane anesthetized spontaneously hypertensive rat.

BACKGROUND: Rodent models are increasingly used to study the development and progression of arterial stiffness. Both the non-invasive Doppler derived Pulse Wave Velocity (PWV) and the invasively determined arterial elastance index (EaI) have been used to assess arterial stiffness in rats and mice, but the need for anesthetic agents to make these in vivo estimates may limit their utility. Thus, we sought to determine: 1) if known differences in arterial stiffness in spontaneously hypertensive rats (SHR) are detectable by PWV and EaI measurements when made under isoflurane anesthesia, and 2) if these two uniquely acquired assessments of arterial elasticity correlate. METHODS: We obtained PWV and EaI measurements in isoflurane anesthetized young and old SHRs, which are known to have significant differences in arterial stiffness. Doppler pulse waves were recorded from carotid and iliac arteries and the distance (D) between probe applantation sites was recorded. Simultaneously, an EKG was obtained, and the time intervals between the R-wave of the EKG to the foot of the Doppler waveforms were measured and averaged over three cardiac cycles. Pulse-transit time (T) of the carotid to iliac artery was determined, and PWV was calculated as Distance (D)/Time (T), where D = the distance from the carotid to the iliac notch and T = (R to iliac foot) - (R to carotid foot). EaI was subsequently determined from pressure volumes loops obtained via left ventricle catheterization. RESULTS: PWV and EaI were found to be significantly faster in the older rats (13.2 ± 2.0 vs. 8.0 ± 0.8 m/sec, p < 0.001; 120 ± 20 vs. 97 ± 16 mmHg/µl/g, p <0.05). Bland-Altman analyses of intra- and inter-observer measures demonstrate a statistically significant relationship between readings (p < 0.0001). PWV and EaI measurements were found to be significantly and positively correlated with a correlation coefficient of 0.53 (p < 0.05). CONCLUSION: Our study suggests that isoflurane administration does not limit Doppler PWV or EaI measures in their ability to provide accurate, in vivo assessments of relative arterial stiffness in isoflurane anesthetised SHR rats. Furthermore, PWV data obtained in these rats correlate well with invasively determined EaI.

Assessment of the early stage of cardiac remodeling of spontaneously hypertensive heart failure rats using the quantitative 3-dimensional analysis provided by acipimox-enhanced FDG-PET.

Spontaneously hypertensive heart failure rats (SHHF) appear to constitute an original model for analyzing the evolution of the metabolic syndrome towards heart failure. This study aimed to characterize early cardiac dysfunction and remodeling in SHHF rats: (1) as compared with spontaneously hypertensive rats (SHR) and with a control group of Kyoto rats (WKY), and (2) by using the 3-dimensional quantitative analysis provided by acipimox-enhanced positron emission tomography (PET) with (18)F-fluorodesoxyglucose (FDG). Left ventricular (LV) ejection fraction (EF) and volume were quantified by automatic software on the FDG-PET images recorded in SHR (n = 20), SHHF (n = 18) and WKY-rats (n = 19) at ages 3 or 10 months old. Arterial blood pressure was determined by cardiac catheterization and cardiac fibrosis was quantified after sacrifice. Blood pressure was similarly elevated in SHR and SHHF rats (respective systolic blood pressures at 10-months: 199 ± 39 vs. 205 ± 2 mmHg), but SHHF rats had higher body mass than SHR rats (at 10-months, 630 ± 36 vs. 413 ± 27 g, p < 0.05) and higher blood levels of cholesterol and of triglycerides. At 3 months, cardiac parameters did not show significant differences between groups but at 10-months, SHHF and SHR rats exhibited an enhancement in myocardial mass and fibrosis associated with a clear decline in LV-EF (SHHF: 46 ± 6 %; SHR: 47 ± 5 %) as compared with WKY (56 ± 6 %, p < 0.01 for both comparisons). Cardiac remodeling of SHHF rats was clearly observable by FDG-PET from the age of 10-months, but in a similar way to that observed for SHR rats, suggesting a predominant role of hypertension.

Simultaneous assessment of autonomic nervous and vascular endothelial functions in a rat model.

Despite the importance of translational medicine in cardiovascular research, rat vascular endothelial function and sympathetic activity assessment remains challenging.This study consisted of two parts: part A examined the consistency of reactive hyperemia-elicited dilatation index(DI) before (DI Original ) and after (DI EEMD ) ensemble empirical mode decomposition (EEMD) using Wistar-Kyoto (WKY)rats (n = 7). Part B compared the endothelial function and heart rate variability of normal WKY rats (group 1, n = 9)with those of spontaneously hypertensive rats (group 2,n = 9) at two time points of development. The SD1/SD2 ratio(SSR) was obtained from Poincaré plot analysis to evaluate sympathetic activities. Using a Bland-Altman plot, part A of the study demonstrated a lower agreement of DI Original than that of DI EEMD . In part B, despite no significant difference in DI EEMD between the two groups at age 10 weeks, DI EEMD was higher in group 1 (2.25 } 0.63 vs. 1.43 } 0.41 for groups 1 and 2, respectively, p = 0.004) at 20 weeks. Although no notable change in SSR existed in group 1 between the twotime points, a significant difference existed in group 2(p < 0.001). In conclusion, using algorithms of Poincaré plot analysis and EEMD, the impact of age and hypertension on rat vascular endothelial function and heart rate variability can be reliably assessed.

Assessment of maximal lactate steady state during treadmill exercise in SHR.

BACKGROUND: Spontaneously hypertensive rats (SHR) are one of the main animal models used for studying the effects of exercise on hypertension. Therefore, the determination of adequate intensity has been essential for secure and optimized exercise prescriptions concerning hypertensive subjects. This study aimed to identify the MLSS in SHR by using a treadmill test to improve the protocols and further prescriptions of exercise intensity. FINDINGS: In order to carry out this determination, SHR (n = 10) animals (~17.5 weeks; 227.4 ± 29.3 g; 172.4 ± 8.1 mmHg systolic blood pressure) were divided into two groups (G1 n = 5; G2 n = 5). Rats underwent a test with three different velocities to determine the MLSS. The MLSS was considered as the highest effort intensity where the blood lactate did not vary more than 1 mmol.L-1 from the 10th to the 25th minute. The MLSS was reached at a velocity of 20 m.min-1 with 3.8 ± 0.5 mmol.L-1 of lactate for G1. Additionally, the results were validated in G2. However, when the test was applied at 25 m.min-1, there was no stabilization of BLC in G1 and G2. CONCLUSIONS: In this study it was possible to identify the MLSS in SHR rats, which is an excellent evaluation tool to control exercise intensity. These data are of considerable importance in studies using physical exercise as a means of research in hypertension and may lead to the intensity of exercise being prescribed more appropriately.

Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions.

OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1) streptozotocin-induced diabetic and control Wistar rats; (2) N-nitro-L-arginine methyl ester (L-NAME) hypertensive and untreated Wistar rats; (3) deoxycorticosterone acetate (DOCA) salt-treated, nephrectomized and salt- and DOCA-treated rats; (4) spontaneous hypertensive rats (SHR) and Wistar Kyoto (WKY) rats; (5) rats with myocardial infarction and shamoperated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester-treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L-arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes), a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better mechanical advantage.