The Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases.

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.

Interplay between caveolin-1 and mineralocorticoid receptor in cardiometabolic disease.

Over the past decades, research has clearly established the important role of the mineralocorticoid receptor (MR) in both renal and extra-renal tissues. Recently, caveolin-1 (Cav-1) has emerged as a mediator of MR signaling in several tissues, with implications on cardiovascular (CV) and metabolic dysfunction. The main structural component of caveolae (plasma membrane invaginations with diverse functions), Cav-1 is a modulator of cardiovascular function, cellular glucose and lipid homeostasis, via its effects on signal transduction pathways that mediate inflammatory responses and oxidative stress. In this review, we present evidence indicating an overlap between the roles of the MR and Cav-1 in cardiometabolic disease and the relevant signaling pathways involved. Furthermore, we discuss the potential use of Cav-1 as a biomarker and/or target for MR-mediated dysfunction.

Bone turnover markers and muscle decay indicator in patients with proximal femur fracture - a case-control study.

Introduction: Fracture of the proximal femur is common in elderly patients, in fact threatening their lives. Age-related sarcopenia may be involved in the imbalance resulting in the injury. Handy and readily accessible biochemical tests would be useful to assess the musculoskeletal system condition in daily practice. The aim of the study was to determine whether there is any relation between muscle decay and fracture of the proximal femur and to assess bone quality in elderly patients. Material and methods: In the study 22 patients who represented the treatment group were hospitalized due to proximal femur fracture. Eighteen patients from the control group with no fracture in their history were admitted to the Internal Medicine Department. Anyone treated for osteoporosis, immune disease affecting protein balance, neoplasm, mental illness, heart failure, or myocardial infarction was excluded from the study. In every case a blood sample from an elbow vein was drawn, collected in EDTA-K2 tubes, and then centrifuged to separate plasma from the whole blood. Subsequently, the concentrations of C-terminal cross-linked telopeptide of type I collagen (CTX-I), sex hormone binding globulin (SHBG) and creatine kinase (CK) in plasma were determined using commercial enzyme-linked immunosorbent assays. Results: The CK plasma concentration differed between the patient groups (p = 0.011). The SHBG plasma concentration was significantly higher in the treatment group (p = 0.006), whereas a slight difference in CTX-I plasma concentration between the groups was found (p = 0.038). No significant correlations between plasma CK, SHBG or CTX-I were found (p > 0.05). Conclusions: Creatine kinase is actually not an appropriate marker for the clinical assessment of muscle tissue quality in patients with or at risk of proximal femur fracture. Analyzing the quality of bone tissue, we can conclude it was poorer in patients with proximal femur fracture than in the control group.

Brain-Derived Neurotrophic Factor (BDNF) Concentration Levels in Cerebrospinal Fluid and Plasma in Patients With Glioblastoma: A Prospective, Observational, Controlled Study.

Objective Glioblastomas (GBMs) are among the most frequent and most malignant of untreatable brain tumors. A GBM marker could accelerate diagnosis and facilitate therapeutic monitoring. This prospective, observational, controlled study compared brain-derived neurotrophic factor (BDNF) levels in cerebrospinal fluid (CSF) and plasma between patients with GBM and a control group. Materials and methods Patients in the observational group underwent elective GBM resection (n=24, 55.8%). Control patients (n=19, 44.2%) had elective brain surgery for an unrelated, non-neoplastic, non-traumatic pathology. We measured BDNF levels in tumors, CSF, and plasma with enzyme-linked immunosorbent assay (ELISA). Peripheral blood and CSF samples were collected before surgery, and tumors were sampled intraoperatively. We analyzed correlations between BDNF levels and patient sex, age, seizures, smoking, diabetes mellitus (DM), and the use of selected antiepileptic drug (AED) and antihypertensive drug groups. Results The mean CSF BDNF concentration was significantly lower in patients with GBM (6.5 pg/mL) than in controls (11.48 pg/mL) (p=0.002). Similarly, the mean plasma BDNF concentration was significantly lower in patients with GBM (288.59 pg/mL) than in controls (574.06 pg/mL) (p=0.0005). None of the examined factors influenced CSF, plasma, or tumor tissue BDNF concentrations (p>0.05). Conclusion Plasma and CSF BDNF levels were significantly lower in adults with GBM than in controls. Thus, CSF and plasma BDNF levels may aid in GBM diagnoses. Further prospective studies are required.

Evaluation of Nitrosative/Oxidative Stress and Inflammation in Heart Failure with Preserved and Reduced Ejection Fraction.

Heart failure (HF) is a complex syndrome characterized by impaired cardiac function. Two common subtypes of HF include heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). In this study, we aimed to evaluate and compare the plasma levels of 3-nitrotyrosine (3-NT)-as a marker of nitrosative/oxidative stress and myeloperoxidase (MPO)-as an indicator of inflammation between HFpEF and HFrEF. Twenty-seven patients diagnosed with HFpEF and twenty-two with HFrEF were enrolled in this study. Additionally, forty-one patients were recruited for the control group. An echocardiographic assessment was conducted, followed by the collection of blood samples from all participants. Subsequently, the levels of 3-NT and MPO were quantified using the ELISA method. Comprehensive clinical characteristics and medical histories were obtained. Circulating levels of 3-NT were significantly higher in the HFpEF patients than in the control and the HFrEF groups. Nitrosative/oxidative stress is significantly intensified in HFpEF but not in HFrEF.

Inflammatory Forms of Cardiomyocyte Cell Death in the Rat Model of Isoprenaline-Induced Takotsubo Syndrome.

Takotsubo syndrome (TTS) is associated with inflammatory response, therefore the aim of the study was to evaluate the presence and dynamics of inflammatory-associated forms of cell death, necroptosis, and pyroptosis in the female rat model of isoprenaline (ISO)-induced TTS. TTS was induced in female Sprague Dawley rats (n = 36) by ISO 150 mg/kg intraperitoneally. Animals were divided into four groups: TTSO (TTS+ovariectomy; n = 10), TTSP (TTS+sham operation; n = 10), CO (0.9% NaCl+ovariectomy; n = 8), CP (0.9% NaCl+sham operation; n = 8). Histopathological analysis, evaluation of plasma concentration, and myocardial expression of pyroptosis- and necroptosis-associated proteins were performed. TTSO and TTSP groups had higher plasma concentrations of interleukin-1ß in comparison with the controls. Low myocardial protein expression of mixed lineage kinase domain-like pseudokinase (MLKL), caspase-1 (Casp-1), and calcium/calmodulin-dependent kinase type II isoform delta (CAMKIIδ) was visible 6 and/or 12 h post-ISO. Twenty-four hours post-ISO, high myocardial and vascular protein expression of CAMKIIδ was visible in TTSO but not TTSP rats, while high myocardial expression of MLKL and Casp-1 was visible both in TTSO and TTSP rats. The course of TTS is associated with activation of inflammatory-associated programmed cell death, necroptosis, and pyroptosis, therefore inflammation may be a primary response occurring simultaneously with cardiomyocyte death in TTS.

Communication of gut microbiota and brain via immune and neuroendocrine signaling.

The gastrointestinal tract of the human is inhabited by about 5 × 1013 bacteria (of about 1,000 species) as well as archaea, fungi, and viruses. Gut microbiota is known to influence the host organism, but the host may also affect the functioning of the microbiota. This bidirectional cooperation occurs in three main inter-organ signaling: immune, neural, and endocrine. Immune communication relies mostly on the cytokines released by the immune cells into circulation. Also, pathogen-associated or damage-associated molecular patterns (PAMPs or DAMPs) may enter circulation and affect the functioning of the internal organs and gut microbiota. Neural communication relies mostly on the direct anatomical connections made by the vagus nerve, or indirect connections via the enteric nervous system. The third pathway, endocrine communication, is the broadest one and includes the hypothalamic-pituitary-adrenal axis. This review focuses on presenting the latest data on the role of the gut microbiota in inter-organ communication with particular emphasis on the role of neurotransmitters (catecholamines, serotonin, gamma-aminobutyric acid), intestinal peptides (cholecystokinin, peptide YY, and glucagon-like peptide 1), and bacterial metabolites (short-chain fatty acids).

A Review of the Roles of Apelin and ELABELA Peptide Ligands in Cardiovascular Disease, Including Heart Failure and Hypertension.

Apelin and ELABELA (ELA), which are peptides belonging to the adipokines group, are endogenous peptide ligands of their receptor, APJ, which together constitute the apelinergic system. The apelinergic system is expressed in numerous human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. Apelin, being the most widely studied member of the apelinergic system, plays a key role in the cardiovascular system and exerts a pleiotropic effect in tissues. Under physiological conditions, the peripheral actions of apelin include augmented cardiac contractility, increased left ventricular stroke volume, vasodilation, increased diuresis, and lowered systemic blood pressure. Multiple studies suggest that activation of the apelinergic system exerts beneficial effects on the treatment of cardiovascular diseases (CVD), including hypertension and heart failure, whereas the silencing of the apelin/APJ axis results in attenuation of inflammatory processes and prevents formation of atherosclerotic plaques. As numerous effects of apelin are not entirely explained, further studies of the cardiovascular actions of apelin and ELA are necessary to help establish effective pharmacological treatments of CVDs. This article aims to review the roles of apelin and elabela peptide ligands in cardiovascular diseases, including heart failure and hypertension.

Sphingolipid metabolism and signaling in cardiovascular diseases.

Sphingolipids are a structural component of the cell membrane, derived from sphingosine, an amino alcohol. Its sphingoid base undergoes various types of enzymatic transformations that lead to the formation of biologically active compounds, which play a crucial role in the essential pathways of cellular signaling, proliferation, maturation, and death. The constantly growing number of experimental and clinical studies emphasizes the pivotal role of sphingolipids in the pathophysiology of cardiovascular diseases, including, in particular, ischemic heart disease, hypertension, heart failure, and stroke. It has also been proven that altering the sphingolipid metabolism has cardioprotective properties in cardiac pathologies, including myocardial infarction. Recent studies suggest that selected sphingolipids may serve as valuable biomarkers useful in the prognosis of cardiovascular disorders in clinical practice. This review aims to provide an overview of the current knowledge of sphingolipid metabolism and signaling in cardiovascular diseases.

Remodeling and Fibrosis of the Cardiac Muscle in the Course of Obesity-Pathogenesis and Involvement of the Extracellular Matrix.

Obesity is a growing epidemiological problem, as two-thirds of the adult population are carrying excess weight. It is a risk factor for the development of cardiovascular diseases (hypertension, ischemic heart disease, myocardial infarct, and atrial fibrillation). It has also been shown that chronic obesity in people may be a cause for the development of heart failure with preserved ejection fraction (HFpEF), whose components include cellular hypertrophy, left ventricular diastolic dysfunction, and increased extracellular collagen deposition. Several animal models with induced obesity, via the administration of a high-fat diet, also developed increased heart fibrosis as a result of extracellular collagen accumulation. Excessive collagen deposition in the extracellular matrix (ECM) in the course of obesity may increase the stiffness of the myocardium and thereby deteriorate the heart diastolic function and facilitate the occurrence of HFpEF. In this review, we include a rationale for that process, including a discussion about possible putative factors (such as increased renin-angiotensin-aldosterone activity, sympathetic overdrive, hemodynamic alterations, hypoadiponectinemia, hyperleptinemia, and concomitant heart diseases). To address the topic clearly, we include a description of the fundamentals of ECM turnover, as well as a summary of studies assessing collagen deposition in obese individuals.

Biochemical and clinical evaluation of endothelial injury after distal or traditional transradial access in percutaneous interventions.

BACKGROUND: Distal transradial access (dTRA) has been proposed as an alternative to traditional transradial access (TRA) in cardiac catheterization. AIMS: The study aimed to compare these two transradial approaches: TRA and dTRA in terms of clinical and biochemical aspects. METHODS: Two hundred patients who qualified for the elective coronary procedure were included. The patients were assigned to one of the groups depending on their vascular access. The groups were compared in terms of perceived pain using the Visual Analogue Scale (VAS), time of gaining access, need for conversion, and local complications. Additionally, in forty patients circulating endothelial injury markers: endothelin 1 (ET-1), interleukin 8 (IL-8), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were assessed. RESULTS: Successful cannulation was obtained in 84 (100%) in the TRA group and in 98 (84%) subjects in the dTRA (P <0.001). dTRA was associated with higher level of pain perceived at the time of gaining vascular approach than TRA; median VAS score (interquartile range [IQR]): 4 (2-5) vs. 2 (2-4) (P = 0.04). The mean time (standard deviation [SD]) needed to cannulate the artery in dTRA was longer than in TRA: 81 (8) seconds vs. 50 (4) seconds (P = 0.04). ET-1 concentration was (SD) 2.08 (0.19) pg/ml [dTRA] vs. 2.00 (0.29) [TRA] pg/ml (P = 0.83); sVCAM-1: 12.71 (3.97) ng/ml vs. 12.86 (4.29) ng/ml (P = 0.98); IL-8: 8.81 (0.42) ng/ml vs. 9.15 (0.52) ng/ml (P = 0.62). Th number of complications after procedures did not differ between these two approaches. CONCLUSIONS: Cannulation of dTRA is associated with a lower success rate and higher pain perceived. dTRA is not inferior to TRA when safety issues and vascular injury are considered.

Gender differences in short- vs. long-term impact of maternal depression following pre-gestational chronic mild stress.

Major Depressive Disorder (MDD) with Peripartum Onset was classified in 2013 by the Diagnostic and Statistical Manual, Fifth Edition (DMS-5) and approved in 2019 by the World Health Organization (WHO). These diagnostic revisions call for the development of new animal models of maternal depression, emphasizing the pregnancy period. We have recently described a novel rat model of maternal MDD with a Peripartum Onset. Exposure to pre-gestational chronic mild stress (CMS) with repeated restrain resulted in maternal depressive-like behavior and impacted offspring's neurodevelopment. The present study examined gender differences in short- vs. long-term neurodevelopmental impact of pre-gestational maternal stress. Stress response was assessed in Sprague Dawley CMS-exposed dams (n=7) by metabolic, hormonal, and behavioral changes and compared to controls dams (n=7). Short-term impact of maternal stress on offspring was examined in terms of metabolic, neurodevelopmental, and behavioral tests in male (n=40) and female (n=35) adolescent offspring on a postnatal day (PD) 48; the long-term impact was assessed in adult male (n=13) and female (n=12) offspring on PD 225. Brain tissue was collected from adolescent and adult offspring for biochemical analysis. Maternal stress was associated with decreased body weight and increased urinary corticosterone during the pre-pregnancy period, but depressive-like behavior was delayed until later in pregnancy. No significant neurodevelopmental changes in suckling male or female offspring derived from the stress-exposed dams were observed. However, adolescent male and female offspring of stress-exposed dams displayed an increased depressive-like behavior and gender-dependent increase in anxiety-like behavior in female offspring. These changes were associated with a brain-region-specific increase in brain-derived neurotrophic factor (BDNF) protein and BDNF receptor (TrkB) mRNA in males. Behavioral changes observed in the adolescents receded in adult male and female offspring. However, plasma BDNF was elevated in stress-exposed adult female offspring. These results suggest that pre-gestational maternal stress is associated with gender-dependent short- vs. long-term neurodevelopmental impact in the offspring. Presented data are of significant public health relevance, and there is an urgent need for further research to confirm these findings and probe the underlying mechanisms.

Multiple Aspects of Inappropriate Action of Renin-Angiotensin, Vasopressin, and Oxytocin Systems in Neuropsychiatric and Neurodegenerative Diseases.

The cardiovascular system and the central nervous system (CNS) closely cooperate in the regulation of primary vital functions. The autonomic nervous system and several compounds known as cardiovascular factors, especially those targeting the renin-angiotensin system (RAS), the vasopressin system (VPS), and the oxytocin system (OTS), are also efficient modulators of several other processes in the CNS. The components of the RAS, VPS, and OTS, regulating pain, emotions, learning, memory, and other cognitive processes, are present in the neurons, glial cells, and blood vessels of the CNS. Increasing evidence shows that the combined function of the RAS, VPS, and OTS is altered in neuropsychiatric/neurodegenerative diseases, and in particular in patients with depression, Alzheimer's disease, Parkinson's disease, autism, and schizophrenia. The altered function of the RAS may also contribute to CNS disorders in COVID-19. In this review, we present evidence that there are multiple causes for altered combined function of the RAS, VPS, and OTS in psychiatric and neurodegenerative disorders, such as genetic predispositions and the engagement of the RAS, VAS, and OTS in the processes underlying emotions, memory, and cognition. The neuroactive pharmaceuticals interfering with the synthesis or the action of angiotensins, vasopressin, and oxytocin can improve or worsen the effectiveness of treatment for neuropsychiatric/neurodegenerative diseases. Better knowledge of the multiple actions of the RAS, VPS, and OTS may facilitate programming the most efficient treatment for patients suffering from the comorbidity of neuropsychiatric/neurodegenerative and cardiovascular diseases.

Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts.

BACKGROUND: Takotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological characteristics in TTS. METHODS: Forty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining. RESULTS: The total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24, 48, 72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084). CONCLUSIONS: The ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient.

New Peptides as Potential Players in the Crosstalk Between the Brain and Obesity, Metabolic and Cardiovascular Diseases.

According to the World Health Organization report published in 2016, 650 million people worldwide suffer from obesity, almost three times more than in 1975. Obesity is defined as excessive fat accumulation which may impair health with non-communicable diseases such as diabetes, cardiovascular diseases (hypertension, coronary artery disease, stroke), and some cancers. Despite medical advances, cardiovascular complications are still the leading causes of death arising from obesity. Excessive fat accumulation is caused by the imbalance between energy intake and expenditure. The pathogenesis of this process is complex and not fully understood, but current research is focused on the role of the complex crosstalk between the central nervous system (CNS), neuroendocrine and immune system including the autonomic nervous system, adipose tissue, digestive and cardiovascular systems. Additionally, special attention has been paid to newly discovered substances: neuropeptide 26RFa, preptin, and adropin. It was shown that the above peptides are synthesized both in numerous structures of the CNS and in many peripheral organs and tissues, such as the heart, adipose tissue, and the gastrointestinal tract. Recently, particular attention has been paid to the role of the presented peptides in the pathogenesis of obesity, metabolic and cardiovascular system diseases. This review summarizes the role of newly investigated peptides in the crosstalk between brain and peripheral organs in the pathogenesis of obesity, metabolic, and cardiovascular diseases.

The Influence of Gut Microbiota on the Cardiovascular System Under Conditions of Obesity and Chronic Stress.

PURPOSE OF REVIEW: Based on the available data, it can be assumed that microbiota is an integral part of the human body. The most heavily colonized area of the human body is the gut, with bacterial accumulation ranging from 101-103 cells/g in the upper intestine to 1011-1012 cells/g in the colon. However, colonization of the gut is not the same throughout, as it was shown that there are differences between the composition of the microbiota in the intestine lumen and in the proximity of the mucus layer. RECENT FINDINGS: Gut microbiota gradient can be differentially regulated by factors such as obesity and chronic stress. In particular, a high fat diet influences the gut microbial composition. It was also found that chronic stress may cause the development of obesity and thus change the organization of the intestinal barrier. Recent research has shown the significant effect of intestinal microflora on cardiovascular function. Enhanced absorption of bacterial fragments, such as lipopolysaccharide (LPS), promotes the onset of "metabolic endotoxemia," which could activate toll-like receptors, which mediates an inflammatory response and in severe cases could cause cardiovascular diseases. It is presumed that the intestinal microbiota, and especially its metabolites (LPS and trimethylamine N-oxide (TMAO)), may play an important role in the pathogenesis of arterial hypertension, atherosclerosis, and heart failure. This review focuses on how gut microbiota can change the morphological and functional activity of the cardiovascular system in the course of obesity and in conditions of chronic stress.

The effect of depressive-like behavior in pregnant rat dams on the cardiovascular system in their offspring.

Maternal depression during pregnancy affects 18-20% of women and is often associated with comorbidities and adverse health outcomes for the offspring. We have previously reported on neurodevelopmental delays in a rat model of maternal depression during pregnancy; current report presents echocardiographic (ECHO) data derived from the same experiment and focuses on cardiovascular response in the offspring to maternal perinatal depression. Rat dams were exposed to chronic mild stress (CMS) with repeated restraint before pregnancy. Cardiac functions were assessed in the 35-day-old offspring, derived from control (CO, n = 11) and stress-exposed dams (SO, n = 16), using echocardiography (ECHO). The expression of cardiac failure marker - B-type natriuretic peptide (BNP) was measured in the myocardium by RT-PCR. ECHO analysis revealed a significant increase in heart rate (HR) and impairment of left ventricular diastolic function parameters. Importantly, a significant increase in mitral valve flow E wave velocity (MVE) and a decrease of mitral valve deceleration time of E wave (MV DT) were observed in SO. The expression of BNP was significantly higher in SO. These results suggest that maternal depression during pregnancy impacts offspring cardiovascular function, and specifically the diastolic cardiac functions of the left ventricle.

Expression of Toll-Like Receptors in the Animal Model of Bladder Outlet Obstruction.

INTRODUCTION: Bladder outlet obstruction (BOO) occurs in more than 20 percent of the adult population and may lead to changes in the structure and function of the bladder. The main objective of the study was to evaluate the expression of Toll-like receptor 4 (TLR 4) and Toll-like receptor 9 (TLR 9) in the animal model of BOO as potential triggers of the inflammation phase in the bladder. In addition, the modulating effect of alpha-1 adrenergic antagonist (tamsulosin) on TLR 4 and TLR 9 expression and inflammatory markers was assessed. Material and Methods. Thirty-two male, 9-week-old Sprague Dawley rats were randomly divided into 4 groups: SOP-sham-operated rats with a placebo (water); SOB-sham-operated rats with an alpha-1 adrenergic antagonist; BOOP-rats with BOO and a placebo; and BOOB-rats with BOO and an alpha-1 adrenergic antagonist. The rats were given a placebo or alpha-1 adrenergic antagonist for 15 days. Next, urine and the bladder were collected from the rats for histopathological and biochemical study. RESULTS: Histopathological analysis showed chronic inflammation without acute inflammation in the bladder. TLR 4 showed positive cytoplasmic reactivity in the urothelium and the smooth muscles of the bladder. TLR 9 showed positive cytoplasmic reactivity only in the urothelium. BOO caused an increase in TLR 4 and TLR 9 expression. Furthermore, treatment with an alpha-1 adrenergic antagonist had no significant effect on TLR 4 and TLR 9 expression in rats with BOO. BOO caused a significant increase in urine concentration of interleukin 6 (IL-6), while alpha-1 antagonist reduced the urine concentration of IL-6 and the concentration of interleukin 18 (IL-18). CONCLUSIONS: The results suggest the participation of TLR 4 and TLR 9 receptors in the induction of inflammation in the bladder, which is the first phase in the development of pathophysiological changes in BOO.

Transthoracic echocardiography: from guidelines for humans to cardiac ultrasound of the heart in rats.

Ultrasound examination of the heart is a cornerstone of clinical evaluation of patients with established or suspected cardiovascular conditions. Advancements in ultrasound imaging technology have brought transthoracic echocardiography to preclinical murine models of cardiovascular diseases. The translational potential of cardiac ultrasound is critically important in rat models of myocardial infarction and ischemia-reperfusion injury, congestive heart failure, arterial hypertension, cardiac hypertrophy, pulmonary hypertension, right heart failure, Takotsubo cardiomyopathy, hypertrophic and dilated cardiomyopathies, developmental disorders, and metabolic syndrome. Modern echocardiographic machines capable of high-frame-rate image acquisition and fitted with high-frequency transducers allow for cardiac ultrasound in rats that yields most of the echocardiographic measurements and indices recommended by international guidelines for cardiac ultrasound in human patients. Among them are dimensions of cardiac chambers and walls, indices of systolic and diastolic cardiac function, and valvular function. In addition, measurements of cardiac dimensions and ejection fraction can be significantly improved by intravenous administration of ultrasound enhancing agents (UEAs). In this article we discuss echocardiography in rats, describe a technique for minimally invasive intravenous administration of UEAs via the saphenous vein and present a step-by-step approach to cardiac ultrasound in rats.