Age- and sex-dependent cardiovascular impact of maternal perinatal stress and altered dopaminergic metabolism in the medulla oblongata of the offspring.

Maternal major depressive disorder with peripartum onset presents health risks to the mother and the developing fetus. Using a rat model of chronic mild stress, we previously reported on the neurodevelopmental impact of maternal perinatal stress on their offspring. This study examined the cardiovascular impact of maternal perinatal stress on their offspring. The cardiovascular impact was assessed in terms of blood pressure and echocardiographic parameters. The results examined by a three-way ANOVA showed a significant association of cardiovascular parameters with maternal perinatal stress and offspring sex and age. Increased blood pressure was observed in adolescent female and adult male offspring of stress-exposed dams. Echocardiography showed an increase in left atrial dimension and a reduction in left ventricular systolic function in adolescent stress-exposed female offspring. Increased interventricular septum thickness at end-diastole and left ventricular diastolic dysfunction were observed in adult stress-exposed male offspring. The underlying mechanisms of cardiovascular impact were examined in stress-exposed adult offspring by assessing the levels of neurotransmitters and their metabolites in the medulla oblongata using high-performance liquid chromatography. A significant decrease in homovanillic acid, a dopamine metabolite and indicator of dopaminergic activity, was observed in adult stress-exposed female offspring. These results suggest a significant sex- and age-dependent impact of maternal stress during the peripartum period on the cardiovascular system in the offspring that extends to adulthood and suggests a multigenerational effect. The presented data urgently need follow-up to confirm their potential clinical and public health relevance.NEW & NOTEWORTHY We demonstrate that maternal perinatal stress is associated with sex- and age-dependent impact on the cardiovascular system in their offspring. The effect was most significant in adolescent female and adult male offspring. Observed changes in hemodynamic parameters and dopaminergic activity of the medulla oblongata are novel results relevant to understanding the cardiovascular impact of maternal perinatal stress on the offspring. The cardiovascular changes observed in adult offspring suggest a potential long-term, multigenerational impact of maternal perinatal stress.

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.

MEDICATION ADHERENCE AND ITS IMPACT ON THE AVERAGE LIFE EXPECTANCY AFTER ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: THE RESULTS OF THE UKRAINIAN STIMUL REGISTRY.

OBJECTIVE: The aim: The present study aimed to evaluate the adherence to medications prior and within a two-year period after ST-segment elevation myocardial infarction (STEMI) and to estimate its impact on the average lifespan of patients after STEMI. PATIENTS AND METHODS: Materials and methods: 1,103 patients with STEMI were enrolled in the prospective Ukrainian STIMUL registry with 24-month follow-up. The relationship between adherence to medical treatment and average lifespan was evaluated. RESULTS: Results: The majority of prior STEMI patients were characterized with high and very high cardiovascular risk. The rate of revascularization was 29.9% (21.5% pPCI, 8.4% fibrinolytic therapy). The main reason for the low level of pPCI was late hospitalization and the inaccessibility of pPCI. This contributed greatly to in-hospital mortality (11.3%). Adherence to all medications progressively decreased (p < 0.001) within 24 months after STEMI. Permanent use of acetylsalicylic acid (ASA) and statins during the two-year follow-up was associated with 7.0% of the mortalities, whereas non-adherence to medications was related to a 15% risk of death (OR 4.2; 95% CI 0.2-0.9; p < 0.05). The average life expectancy with regular use of ASA and statins within 24 months after STEMI was 62.3 ± 1.1 years (95% CI 60.1-64.4; p < 0.05) and 61.2 ± 0.9 years with non-regular use of ASA and statins (95% CI 59.4-62.9; p < 0.05). CONCLUSION: Conclusions: Adherence to evidence-based medicines was low in the STIMUL population both prior and after STEMI. This worsened cardiovascular prognosis and reduced average lifespan by one year within the following two years after STEMI.

Evaluation and Comparison of the STIMUL Extended and Simplified Risk Scores for Predicting Two-Year Death in Patients Following ST-Segment Elevation Myocardial Infarction.

Background and Objectives: The management of ST-segment elevation myocardial infarction (STEMI) requires a patient's long-term risk to be estimated. The objective of this study was to develop extended and simplified models of two-year death risk estimation following STEMI that include and exclude cardiac troponins as prognostic factors and to compare their performance with each other. Materials and Methods: Extended and simplified multivariable logistic regression models were elaborated using 1103 patients with STEMI enrolled and followed up in the STIMUL (ST-segment elevation Myocardial Infarctions in Ukraine and their Lethality) registry. Results: The extended STIMUL risk score includes seven independent risk factors: age; Killip class ≥ II at admission; resuscitated cardiac arrest; non-reperfused infarct-related artery; troponin I ≥ 150.0 ng/L; diabetes mellitus; and history of congestive heart failure. The exclusion of cardiac troponin in the simplified model did not influence the predictive value of each factor. Both models divide patients into low, moderate, and high risk groups with a C-statistic of 0.89 (95% CI 0.84-0.93; p < 0.001) for the extended STIMUL model and a C-statistic of 0.86 (95% CI 0.83-0.99; p < 0.001) for the simplified model. However, the addition of the level of troponin I to the model increased its prognostic value by 10.7%. Conclusions: The STIMUL extended and simplified risk estimation models perform well in the prediction of two-year death risk following STEMI. The simplified version may be useful when clinicians do not know the value of cardiac troponins among the population of STEMI patients.

Central interaction between the apelinergic and vasopressinergic systems in the regulation of the haemodynamic parameters in rats maintained on a high-fat diet.

A high-fat diet can affect the central activity of the apelinergic and vasopressinergic systems, which can have a significant impact on cardiovascular regulation. The aim of the study was to investigate the role of the central interaction between apelin and vasopressin in the regulation of the cardiovascular system in Sprague Dawley rats maintained on a normal-fat diet (NFD) or on a high-fat diet (HFD). The animals were instrumented with a cannula implanted into the left cerebral ventricle for intracerebroventricular (ICV) infusions of saline (0.9% NaCl), apelin-13 (APLN-13), V1a receptor antagonist (V1aRANT) APJ receptor antagonist (F13A), vasopressin (AVP); and with a catheter placed within the femoral artery for mean arterial blood pressure and heart rate monitoring. Blood, the hypothalamus and the medulla oblongata were collected for biochemical analysis. The hypertensive effect of APLN-13 was blocked by a prior ICV infusion of V1aRANT, only in the NFD rats. However, the hypertensive effect of AVP was blocked by the prior ICV infusion of F13A in both the NFD and HFD rats. A HFD caused an increase in the protein level of APJ and V1a receptors, both in the hypothalamus and the medulla oblongata. This study confirms the presence of an interaction between both peptides in the central regulation of the cardiovascular system in rats on a NFD or a HFD.

Interaction of Orexin A and Vasopressin in the Brain Plays a Role in Blood Pressure Regulation in WKY and SHR Rats.

BACKGROUND Orexin A (OXA) and vasopressin (AVP) exert a central hypertensive effect due to an increase in sympathetic nerve activity. To date, little is known about the interaction of these 2 neuropeptides in the central regulation of blood pressure. The present study compared the consequences of infusion into the left cerebral ventricle (ICV) of OXA on mean arterial blood pressure (MABP) in normotensive (WKY) and spontaneously hypertensive (SHR) rats, and explored whether the central pressor action of OXA in these 2 strains depends on activation of brain AVP V1a receptors (V1aR). MATERIAL AND METHODS Ten groups of experiments were performed on 12-week-old WKY and SHR rats implanted with ICV cannulas for infusion of OXA (3 nmol) and V1aR antagonist (V1aRANT, 500 ng), administered separately and together. Levels of V1aR and OXR in the medulla oblongata of WKY and SHR rats were compared in separate series. RESULTS We found that: 1) OXA significantly increased MABP only in WKY rats, 2) V1aRANT prevented an increase in MABP induced by OXA in WKY rats and decreased MABP in SHR rats, 3) OXA abolished the hypotensive action of V1aRANT in SHR rats, and 4) SHR rats had significantly higher levels of OX1R and V1aR proteins and OX1R mRNA in the brain medulla. CONCLUSIONS The present study shows that OXA and AVP can interact in the brain to affect blood pressure regulation, and that this interaction differs in normotension and hypertension.

The role of apelin in central cardiovascular regulation in rats with post-infarct heart failure maintained on a normal fat or high fat diet.

Based on the available literature, it can be assumed that in cases of post-infarct heart failure (HF) and obesity, a significant change in the central regulation of the cardiovascular system takes place with, among others, the involvement of the apelinergic system. The main objective of the present study was to clarify the role of apelin-13 in the central regulation of the cardiovascular system in Sprague Dawley rats with HF or sham operated (SO) and fed on a normal fat (NFD) or a high fat diet (HFD). The study was divided into two parts: Part I, hemodynamic studies; and Part II, biochemical and molecular studies. The animals were subjected to the following research procedures. Part I and II: feeding NFD or HFD; experimental induction of HF or SO; Part I: intracerebroventricular (ICV) infusion of the examined substances, monitoring of mean arterial blood pressure (MABP) and heart rate (HR); Part II: venous blood and tissue samples collected. ICV infusion of apelin-13 caused significantly higher changes in ΔMABP in the SO NFD group. No changes were noted in ΔHR in any of the studied groups. Apelin and apelin receptor (APJ) mRNA expression in the brain and adipose tissues was higher in the HF rats. HFD causes significant increase in expression of apelin and APJ mRNA in the left ventricle. In conclusion, HF and HFD appear to play an important role in modifying the activity of the central apelinergic system and significant changes in mRNA expression of apelin and APJ receptor.

High-fat diet and chronic stress reduce central pressor and tachycardic effects of apelin in Sprague-Dawley rats.

Central application of apelin elevates blood pressure and influences neuroendocrine responses to stress and food consumption. However, it is not known whether the central cardiovascular effects of apelin depend also on caloric intake or chronic stress. The purpose of the present study was to determine the effects of intracerebroventricular administration of apelin on blood pressure (mean arterial blood pressure) and heart rate in conscious Sprague-Dawley rats consuming either a normal-fat diet (NFD) or high-fat diet (HFD) for 12 weeks. During the last 4 weeks of the food regime, the rats were exposed (NFDS and HFDS groups) or not exposed (NFDNS and HFDNS groups) to chronic stress. Each group was divided into two subgroups receiving intracerebroventricular infusions of either vehicle or apelin. Apelin elicited significant increase of mean arterial blood pressure and heart rate in the NFDNS rats. This effect was abolished in the HFDNS, HFDS and NFDS groups. HFD resulted in a significant elevation of blood concentrations of total cholesterol, triglycerides glucose and insulin. Chronic stress reduced plasma concentration of total and high-density lipoprotein cholesterol, and increased plasma corticosterone concentration and APJ receptor mRNA expression in the hypothalamus, whereas a combination of a HFD with chronic stress resulted in the elevation of plasma triglycerides, total cholesterol and low-density lipoprotein cholesterol, and in increased plasma corticosterone concentration, apelin concentration and APJ receptor mRNA expression in the hypothalamus. It is concluded that a HFD and chronic stress result in significant suppression of the central pressor action of apelin, and cause significant though not unidirectional changes of metabolic and endocrine parameters.

Zero-fluoroscopy catheter ablation of premature ventricular contractions: comparative outcomes from the right ventricular outflow tract and other ventricular sites.

BACKGROUND: The three-dimensional electroanatomic mapping (EAM) system allows performing catheter ablation (CA) without fluoroscopy in patients with premature ventricular contractions (PVCs). The right ventricle outflow tract (RVOT) location is favorable for performing zero-fluoroscopy CA. Non-RVOT zero-fluoroscopy CA is a challenging procedure. The study aimed to evaluate the efficacy and safety of zero-fluoroscopy CA using the EAM in patients with PVCs from RVOT and non-RVOT. METHODS: Completely zero-fluoroscopy CA of PVCs guided by EAM was performed in 107 patients with PVCs. 54 patients underwent zero-fluoroscopy RVOT CA. The remaining 53 patients underwent zero-fluoroscopy non-RVOT CA. Demographic and clinical baseline characteristics, procedure parameters, and follow-up were obtained from medical records. Primary outcomes were the acute and the permanent success rate (12-month follow-up), complications, and procedure time. RESULTS: There were no significant differences between groups regarding baseline characteristics. Acute procedural success was achieved in 52 patients (94,44%) in the RVOT zero-fluoroscopy CA group and in 45 patients (86,54%) in the non-RVOT zero-fluoroscopy CA group (ns). A long-term success rate was achieved in 50 patients (90,74%) in the RVOT zero-fluoroscopy CA group and in 44 patients (84,62%) in the non-RVOT zero-fluoroscopy CA group (ns). The median procedure time was 80.5 minutes in the RVOT group and 90 minutes in the non-RVOT group (ns). There were two complications in the non-RVOT group (ns). CONCLUSIONS: There were no differences in procedure time efficacy and safety zero-fluoroscopy ablation between RVOT and non-RVOT locations. Non-fluoroscopy CA of PVCs is a feasible, safe, and efficient procedure.

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.

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.

Are medical students interested in research? - students' attitudes towards research.

BACKGROUND: Throughout the years significant progress has been observed in all medical fields. It was possible to achieve thanks to a wide range of scientists, including physician-scientists. However, in recent years their number is significantly declining. Thus we have aimed to explore the attitudes of medical students towards research. METHODS: The cross-sectional study was conducted among medical students of Medical University of Warsaw between the 1st and 23rd of December 2019. Survey examining scientific interests and activities, opinions on selected research issues, and perception of potential barriers to research activities has been distributed to 838 students and collected from 695 (391 students of the 2nd year and 304 of the 5th year) with a response rate of 82.9%. Descriptive statistics, the Chi-squared test, U-Mann-Whitney, and Kruskal-Wallis tests were used for between-group comparisons. The differences were considered statistically significant if the p values were <.05. RESULTS: 55.2% of responders rated their scientific interests in high school as high, with no significant differences between 2nd and 5th-year students. 33.8% (n = 233) of all students plan to pursue research activity after graduation, and 52.8% (n = 360) plan to obtain PhD title. Students who presented higher scientific interests in high school more often were involved in research projects at the university (24.7% vs 17.5%, p = .044), and showed higher interest in pursuing a research career (37.9% vs 28.9%, p = .02). Lack of time and knowledge on starting a research project were perceived as the main barriers to scientific work. CONCLUSIONS: Many medical students express research interests, are involved in scientific projects, and plan to pursue their careers in this direction. There is a majority of students with lower attitudes towards research. Medical universities should consider adapting their curricula accordingly to accommodate the needs of both groups and respond to the shortage of physicians working in clinics and research.KEY MESSAGESOne-third of medical students plan to pursue career in medical research after graduation.Students who presented higher scientific interests in the high school are more often involved in research projects at the university and show higher interest in pursuing a research career.According to medical students, lack of time, resources and funding and insufficient knowledge how to start a research project are the most important barriers to research activity.

Brain vasopressin V(1) receptors contribute to enhanced cardiovascular responses to acute stress in chronically stressed rats and rats with myocardial infarcton.

The present study was designed to determine the role of central vasopressin 1 receptors (V(1)R) in the regulation of cardiovascular parameters in chronically stressed infarcted rats and sham-operated rats under resting conditions and during exposure to acute alarming stress. The experiments were performed on four groups of conscious sham-operated and four groups of infarcted rats subjected to intraventricular infusion of either vehicle or a V(1)R antagonist (V(1)RANT). Two groups of infarcted and two groups of sham-operated rats were subjected to mild chronic stressing. Mean arterial blood pressure (MABP) and heart rate (HR) were determined under resting conditions and after exposure to acute stress (air jet). During vehicle infusion, MABP and HR increases in response to acute stress in the infarcted rats not subjected to chronic stress, and in the infarcted and sham-operated chronically stressed rats, were significantly greater than in the sham-operated rats not exposed to chronic stress. However, MABP and HR responses to acute stress in the chronically stressed infarcted rats and chronically stressed sham-operated rats did not differ. V(1)RANT abolished differences in cardiovascular responses to acute stress between the experimental groups. Resting cardiovascular parameters were not affected by any of the experimental treatments. It is concluded that chronic stressing enhances the pressor and tachycardic responses to acute stress in the sham-operated rats but does not further intensify these responses in infarcted rats.The results provide evidence that central V(1)Rs are involved in potentiation of cardiovascular responses to acute stress in chronically stressed rats, infarcted rats, and chronically stressed infarcted rats.

The influence of post-infarct heart failure and high fat diet on the expression of apelin APJ and vasopressin V1a and V1b receptors.

Vasopressin and apelin are reciprocally regulated hormones which are implicated in the pathophysiology of heart failure and the regulation of metabolism; however, little is known about their interactions under pathological conditions. In this study, we determined how post-infarct heart failure (HF) and a high fat diet (HFD) affect expression of the apelin APJ receptor (APJR) and the V1a (V1aR) and V1b (V1bR) vasopressin receptors in the hypothalamus, the heart, and the retroperitoneal adipose tissue. We performed experiments in male 4-week-old Sprague Dawley rats. The animals received either a normal fat diet (NFD) or a HFD for 8 weeks, then they underwent left coronary artery ligation to induce HF or sham surgery (SO), followed by 4 weeks of NFD or HFD. The HF rats showed higher plasma concentration of NT-proBNP and copeptin. The HF reduced the APJR mRNA expression in the hypothalamus. The APJR and V1aR protein levels in the hypothalamus were regulated both by HF and HFD, while the V1bR protein level in the hypothalamus was mainly influenced by HF. APJR mRNA expression in the heart was significantly higher in rats on HFD, and HFD affected the reduction of the APJR protein level in the right ventricle. The regulation of APJR, V1aR and V1bR expression in the heart and the retroperitoneal adipose tissue were affected by both HF and HFD. Our study demonstrates that HF and HFD cause significant changes in the expression of APJR, V1aR and V1bR, which may have an important influence on the cardiovascular system and metabolism.

Differential sensitisation to central cardiovascular effects of angiotensin II in rats with a myocardial infarct: relevance to stress and interaction with vasopressin.

The purpose of the present study was to elucidate if rats with myocardial infarction manifest altered responsiveness to central cardiovascular effects of low doses of angiotensin II (ANG II), and if ANG II and vasopressin (VP) cooperate in the central regulation of cardiovascular functions at rest and during stress. Conscious Sprague-Dawley rats with myocardial infarction induced by left coronary artery ligation, or sham-ligated (SL) controls were infused intracerebroventricularly with artificial cerebrospinal fluid (aCSF), ANG II, ANG II + VP or ANG II + V1a receptor antagonist (V1ANT) 4 weeks after cardiac surgery. In the infarcted but not in the SL rats, the resting mean arterial blood pressure (MABP) was significantly elevated by infusions of ANG II and ANG II + VP, while infusion of ANG II + V1ANT was not effective. During administration of aCSF, the pressor, and tachycardic responses to an air-jet stressor were significantly greater in the infarcted than in the SL rats. In the SL rats, the pressor responses to the stressor were significantly greater during infusions of ANG II, ANG II + VP and ANG II + V1ANT than during infusion of aCSF. The tachycardic response in the SL rats was enhanced only by the combined infusion of ANG II + VP. In the infarcted rats, the pressor and the tachycardic responses to the stressor were similar in all groups. It is concluded that: (1) under resting conditions the infarcted rats manifest sensitisation to the central pressor effect of ANG II and that this effect depends on concomitant stimulation of V1a VP receptors, (2) central ANG II may enhance the pressor response to an alarming stressor in the SL rats through an action which does not depend on the concomitant stimulation of V1a receptors, (3) the cooperative action of ANG II and VP is required for intensification of the tachycardic response to the alarming stressor in the SL rats and (4) exaggeration of the cardiovascular responses to the alarming stressor in the infarcted rats cannot be further augmented by an additional stimulation of central ANG II receptors or combined stimulation of ANG II and VP receptors.

[Myocardial structure and function in patients with metabolic syndrome--echocardiographic and ergospirometric assessment]. / Zespób metaboliczny a budowa i funkcja miesnia sercowego--ocena echokardiograficzna i ergospirometryczna.

UNLABELLED: Presently a lot of studies focus on metabolic syndrome. There are new studies regarding the relationship between metabolic syndrome (MS) and changes in myocardial structure and function and subsequent development of heart failure. The aim of the study was to assess the myocardial structure and function, particularly diastolic function, and to evaluate the exercise capacity in patients with metabolic syndrome. MATERIAL AND METHODS: 53 patients with MS (defined according to NCEP ATP III criteria) and 33 individuals in control group were enrolled into the study. Echocardiographic examination (with evaluation of morphologic parameters, ejection fraction and diastolic function) and ergospirometry (to objectively assess the exercise capacity) were performed in all patients. RESULTS: In patients with MS hypertension (100%) and abdominal obesity (98%) were the most frequent. In the studied group significantly lower E/A ratio (describing left ventricle relaxation) was observed in comparison to control group (E/A 1.0 +/- 0.05 vs. 1.29 +/- 0.11; p < 0.05). Diastolic dysfunction assessed with the use of E/A worsened with the number of metabolic syndrome elements (1.07 vs. 0.96 vs. 0.87 for 3, 4 and 5 metabolic syndrome elements respectively). Lower peak oxygen uptake (VO2 peak) was observed in patients with MS in comparison to control group (24 +/- 0.75 vs. 27 +/- 1.52 ml/kg/min; p < 0.05). There was the tendency to higher VE-CO2 slope index in patients with MS in comparison to control group (27 +/- 0.45 vs. 25 +/- 0.7; p = 0.057). VE-CO2 slope increased with the increase of the number of MS elements (26 vs. 28 vs. 29 for 3, 4 and 5 metabolic syndrome elements). There was significant positive correlation between E/A ratio and VO2 peak (r = 0.27; p < 0.05) and significant negative correlation between E/A ratio and VE-CO2 slope (r = -0.37; p < 0.01). CONCLUSIONS: In patients with metabolic syndrome the significant decrease of exercise capacity assessed by ergospirometry and lower values of E/A ratio (that describes left ventricle relaxation) in comparison to control group. It seems that there is casual relation between these parameters and one may conclude that patients with MS are at risk of development of left ventricle dysfunction and in consequence heart failure.

Effect of Chronic Kidney Disease on Changes in Vasopressin System Expression in the Kidney Cortex in Rats with Nephrectomy.

It is believed that the vasopressinergic system plays an important role in the pathogenesis of chronic kidney disease (CKD). The aim of this study was to evaluate the effect of CKD on changes in vasopressin system expression in the kidney cortex in rats with nephrectomy. The study was performed on 4 groups of Sprague Dawley (SPRD) rats: a control group (CN), 1/2 nephrectomy (N1/2), 2/3 nephrectomy (N2/3), and 5/6 nephrectomy (N5/6). Blood and the kidney cortex were collected to evaluate plasma copeptin concentrations and mRNA expressions of V1a vasopressin receptors (V1aR) and V2 vasopressin receptors (V2R) and V1aR, V2R, and aquaporin 2 (AQP2) protein levels. V1aR and V2R mRNA expression in the kidney cortex was significantly lower in the CN group compared with the other groups. In contrast, the V1aR, V2R, and AQP2 protein levels were significantly higher in the CN group compared with all of the nephrectomized groups. Plasma copeptin concentration was significantly lower in the CN group than in the nephrectomized groups. CKD caused significant changes in the expression of the vasopressinergic system. Further research is needed to explain the mechanisms of the impact of the vasopressinergic system on the kidney in CKD.

Interaction of AT1 receptors and V1a receptors-mediated effects in the central cardiovascular control during the post-infarct state.

UNLABELLED: Experimental objectives. Because myocardial infarct is associated with overactivation of brain angiotensin II (ANG II) and vasopressin (AVP) V1a receptors we decided to determine whether AT1 and V1a receptors-mediated effects of ANG II and AVP interact in central cardiovascular control during the post-infarct state. Four groups of infarcted and four groups of sham-operated conscious rats entered the study. Results. In the infarcted rats cerebroventricular infusion of AT1 (AT1ANT, losartan) and V1a antagonist {V1aANT,d(CH(2))(5)[Tyr(Me)(2)Ala-NH(2)(9)]VP} and combined infusion of both these compounds performed 4 weeks after induction of the infarct significantly and comparably reduced mean arterial blood pressure (MABP) in comparison to control experiments (artificial cerebrospinal fluid infusion). In the sham rats MABP was not affected by any of the infusions. In control experiments MABP and HR responses to an alarming air jet stress were significantly higher in the infarcted than in the sham rats. Both responses were normalized with the same effectiveness by administration of AT1ANT, V1aANT and AT1ANT+V1aANT. In the sham rats administration of these compounds did not affect MABP and HR responses to stress. CONCLUSION: The results provide evidence for interaction of AT1 and V1a receptors-mediated effects of ANG II and AVP in the central cardiovascular control during the post-infarct state.