These results provide mechanistic evidence that AngII-induced hypertensive effects are mediated, at least in part, by brain TLR4, and that brain TLR4 blockade attenuates AngII-induced hypertensive response, possibly via down-regulation of myocardial inflammatory molecules and sympathetic activity.

Background: The impact of pulmonary hypertension (PH) on right ventricular systolic function is difficult to assess. Tricuspid annular plane systolic excursion (TAPSE) is an echocardiographic measurement of right ventricular systolic function and a strong predictor of outcome in human PH patients.Hypothesis/Objectives: Determine a reference range for TAPSE in healthy dogs, and quantify TAPSE in dogs with PH. It is hypothesized that TAPSE is lower in dogs with PH compared with a reference group, and decreases as PH worsens.Animals: Fifty normal dogs and 30 dogs with PH. Methods: TAPSE was measured by 2-dimensional echocardiography-guided M-mode from the left apical 4-chamber view. Peak systolic tricuspid valve regurgitation jet velocity was measured by continuous-wave Doppler to estimate right ventricular-to-right atrial pressure gradient. PH was subjectively classified as mild, moderate, and severe.Results: There was a curvilinear correlation between TAPSE and body weight. The upper and lower limits of the 95% reference interval were determined by quantile regression. Interobserver and intraobserver agreement was adequate with a coefficient of variation <10%. There were significant differences when comparing dogs with PH and the healthy group, as well as between the PH subgroups (P < .01), except between dogs with mild and moderate PH (P = .99). Only dogs in the severe PH group had TAPSE values that were mostly below the lower limit of the reference interval.Conclusions and Clinical Importance: TAPSE is easily obtainable with acceptable inter and intraobserver agreement. TAPSE is decreased in PH and below the reference interval in most dogs with severe PH.

BackgroundMetabolic syndrome (MetS) is characterized by a cluster of health factors that indicate a higher risk for cardio-renal diseases. Recent evidence indicates that antioxidants from berries are alternative to attenuate oxidative stress and inflammation. We tested the hypothesis that inflammation-induced renal damage is triggered by the activation of TLR4, and subsequent modulation of redox-sensitive molecules and mitogen-activated protein kinase (MAPK) pathway.MethodsFive-week old lean and obese Zucker rats (LZR and OZR) were fed a blueberry-enriched diet or an isocaloric control diet for 15 weeks. A glucose tolerance test and acute renal clearance experiments were performed. Gene and protein expression levels for TLR4, cytokines and phosphorylation of ERK and p38MAPK were measured. Kidney redox status and urinary albumin levels were quantified. Renal pathology was evaluated histologically.ResultsControl OZR exhibited lower glucose tolerance; exacerbated renal function parameters; increased oxidative stress. Gene and protein expression levels of TLR4 were higher and this was accompanied by increased renal pathology with extensive albuminuria and deterioration in antioxidant levels in OZR. In addition, OZR had increased phosphorylation of ERK and p38MAPK. Blueberry-fed OZR exhibited significant improvements in all these parameters compared to OZR.ConclusionTLR4-MAPK signaling pathway is a key to the renal structural injury and dysfunction in MetS and blueberry (BB) protect against this damage by inhibiting TLR4.SignificanceThis is the first study to put forth a potential mechanism of TLR4-induced kidney damage in a model of MetS and to elucidate a downstream mechanism by which blueberry exert their reno-protective effects.

AimsThis study sought to investigate the effects of physical detraining on blood pressure (BP) and cardiac morphology and function in hypertension, and on pro- and anti-inflammatory cytokines (PICs and AIC) and oxidative stress within the brain of hypertensive rats.Methods and ResultsHypertension was induced in male Sprague-Dawley rats by delivering AngiotensinII for 42 days using implanted osmotic minipumps. Rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise (ExT) for 42 days, whereas, detrained groups underwent 28 days of exercise followed by 14 days of detraining. BP and cardiac function were evaluated by radio-telemetry and echocardiography, respectively. At the end, the paraventricular nucleus (PVN) was analyzed by Real-time RT-PCR and Western blot. ExT in AngII-infused rats caused delayed progression of hypertension, reduced cardiac hypertrophy, and improved diastolic function. These results were associated with significantly reduced PICs, increased AIC (interleukin (IL)-10), and attenuated oxidative stress in the PVN. Detraining did not abolish the exercise-induced attenuation in MAP in hypertensive rats; however, detraining failed to completely preserve exercise-mediated improvement in cardiac hypertrophy and function. Additionally, detraining did not reverse exercise-induced improvement in PICs in the PVN of hypertensive rats; however, the improvements in IL-10 were abolished.ConclusionThese results indicate that although 2 weeks of detraining is not long enough to completely abolish the beneficial effects of regular exercise, continuing cessation of exercise may lead to detrimental effects.

Indicators of pulmonary hypertension in dogs examined with thoracic computed tomography (CT) are not well established in the veterinary literature. In humans, the main pulmonary artery to aortic diameter ratio (MPA:Ao) measured via CT, has been shown to be more sensitive than echocardiographic variables for predicting presence and severity of pulmonary hypertension, in some cases. In veterinary literature, the MPA:Ao has been determined echocardiographically to have an upper limit of about 1:1. Measurement of this ratio has not been described in dogs using CT. The objectives of this cross-sectional, prospective study were to compare echocardiographic measurement of MPA:Ao with that obtained via CT, determine if measurement of MPA:Ao via CT is repeatable and reproducible, and determine the effect of respiration and contrast administration on the measurement of MPA:Ao via CT. Ten healthy dogs without pulmonary hypertension were anesthetized to undergo thoracic CT using three protocols and echocardiography. The MPA:Ao was measured three times by three observers for each of the three CT protocols and compared to echocardiographic measurements. The mean MPA:Ao measured among all observers and CT protocols was 1.108 ± 0.152 (SD). The effect of CT scan protocol on MPA:Ao significantly differed among the three methods (P = 0.0014), where expiratory scans had lower MPA:Ao than inspiratory scans. The ratio measured on inspiratory CT scans consistently overestimated MPA:Ao when compared to echocardiography (bias = 0.226). Findings did not support the echocardiographically derived upper limit of MPA:Ao as an upper limit for determination of main pulmonary arterial enlargement on CT.