Heart Force Of Contraction Research Articles

9246 Mineralocorticoid Receptor Regulation of the Molecular Clock in Cardiomyocytes Is Modulated by Time of Day

Abstract Disclosure: M. Kanki: None. S. Heanue: None. P.J. Fuller: None. T.J. Cole: None. C.D. Clyne: None. M.J. Young: None. The onset of cardiovascular disease events peaks in the early morning, which coincides with the diurnal surge in aldosterone and cortisol. Aldosterone-induced mineralocorticoid receptor (MR) activation in cardiomyocytes has established roles in cardiac pump function and electrophysiology and inappropriate MR activation promotes cardiovascular pathophysiology in experimental models of hypertension and heart failure and in the clinic. Recently, we identified a novel role for MR in regulating the circadian clock signalling network in cardiac cells and showed that time of day modulates MR activation in the heart. Whether time-of-day-dependent MR regulation of circadian clocks in cardiomyocytes modulates temporal expression of key functional pathways is unknown. Therefore, we sought to identify cardiac responsiveness to MR stimulation at lights on (7AM) versus lights off (7PM) in ≥8-week old male wildtype (WT) and cardiomyocyte-MR knockout (MyoMRKO) mice. RNA-seq analyses revealed that aldosterone (50 ug/kg) administered at 7PM but not at 7AM significantly enriched transcription of genes associated with 52 biological processes including “Circadian rhythm”, “Reg. of blood pressure”, “Ion transport” and “Reg. of the force of heart contraction” in WT hearts (p<0.05 versus 7PM vehicle-injected WT mice). These outcomes were absent in hearts isolated from MyoMRKO mice administered aldosterone at 7AM or 7PM. Analysis by RT-qPCR revealed that aldosterone versus vehicle administered at 7AM increased expression of circadian Period (Per) and Thyrotroph embryonic factor (Tef) genes in WT hearts, which was lost in MyoMRKO mice. Whole transcriptome analysis also detected significant enrichment in “Cell-cell signalling”, “Positive regulation of cell differentiation”, “Positive regulation of glucose metabolic process”, “Regulation of sodium ion transport”, and “Inflammatory response" processes between 7AM and 7PM in WT hearts, which was also lost in MyoMRKO mice. Our data show that MR transcription of genes associated with circadian rhythms and ion transport is temporally regulated, and demonstrates specificity for cardiomyocyte-MR regulation of circadian clocks. Taken together, we highlight that the role for cardiomyocyte-MR regulation of cardiac electrophysiology, heart rate variability, and metabolic processes is time-of-day-dependent. Understanding temporal coordination of MR activation in physiology and pathophysiology may inform new strategies for optimising MR-directed therapies in patients with heart disease. Presentation: 6/2/2024

7763 Mineralocorticoid Receptor Regulation of the Molecular Clock in Cardiomyocytes Is Modulated by Time of Day

Abstract Disclosure: M. Kanki: None. S. Heanue: None. P.J. Fuller: None. T.J. Cole: None. C.D. Clyne: None. M.J. Young: None. The onset of cardiovascular disease events peaks in the early morning, which coincides with the diurnal surge in aldosterone and cortisol. Aldosterone-induced mineralocorticoid receptor (MR) activation in cardiomyocytes has established roles in cardiac pump function and electrophysiology and inappropriate MR activation promotes cardiovascular pathophysiology in experimental models of hypertension and heart failure and in the clinic. Recently, we identified a novel role for MR in regulating the circadian clock signalling network in cardiac cells and showed that time of day modulates MR activation in the heart. Whether time-of-day-dependent MR regulation of circadian clocks in cardiomyocytes modulates temporal expression of key functional pathways is unknown. Therefore, we sought to identify cardiac responsiveness to MR stimulation at lights on (7AM) versus lights off (7PM) in ≥8-week old male wildtype (WT) and cardiomyocyte-MR knockout (MyoMRKO) mice. RNA-seq analyses revealed that aldosterone (50 ug/kg) administered at 7PM but not at 7AM significantly enriched transcription of genes associated with 52 biological processes including “Circadian rhythm”, “Reg. of blood pressure”, “Ion transport” and “Reg. of the force of heart contraction” in WT hearts (p<0.05 versus 7PM vehicle-injected WT mice). These outcomes were absent in hearts isolated from MyoMRKO mice administered aldosterone at 7AM or 7PM. Analysis by RT-qPCR revealed that aldosterone versus vehicle administered at 7AM increased expression of circadian Period (Per) and Thyrotroph embryonic factor (Tef) genes in WT hearts, which was lost in MyoMRKO mice. Whole transcriptome analysis also detected significant enrichment in “Cell-cell signalling”, “Positive regulation of cell differentiation”, “Positive regulation of glucose metabolic process”, “Regulation of sodium ion transport”, and “Inflammatory response" processes between 7AM and 7PM in WT hearts, which was also lost in MyoMRKO mice. Our data show that MR transcription of genes associated with circadian rhythms and ion transport is temporally regulated, and demonstrates specificity for cardiomyocyte-MR regulation of circadian clocks. Taken together, we highlight that the role for cardiomyocyte-MR regulation of cardiac electrophysiology, heart rate variability, and metabolic processes is time-of-day-dependent. Understanding temporal coordination of MR activation in physiology and pathophysiology may inform new strategies for optimising MR-directed therapies in patients with heart disease. Presentation: 6/2/2024

Estrogen contamination increases vulnerability of amphibians to the deadly chytrid fungus

Aquatic contaminants and infectious diseases are among the major drivers of global amphibian declines. However, the interaction of these factors is poorly explored and could better explain the amphibian crisis. We exposed males and females of the Brazilian Cururu Toad, Rhinella icterica, to an environmentally relevant concentration of the estrogen 17-alpha-ethinylestradiol (an emerging contaminant) and to the chytrid infection (Batrachochytrium dendrobatidis), in their combined and isolated forms, and the ecotoxicity was determined by multiple biomarkers: cutaneous, hematological, cardiac, hepatic, and gonadal analysis. Our results showed that Cururu toads had many physiological alterations in response to the chytrid infection, including the appearance of cutaneous Langerhans's cells, increased blood leukocytes, increased heart contraction force and tachycardia, increased hepatic melanomacrophage cells, which in turn led to gonadal atrophy. The estrogen, in turn, increased the susceptibility of the toads to the chytrid infection (higher Bd loads) and maximized the deleterious effects of the pathogen: reducing leukocytes, decreasing the contraction force, and causing greater tachycardia, increasing hepatic melanomacrophage cells, and leading to greater gonadal atrophy, which were more extreme in females. The exposure to estrogen also revealed important toxicodynamic pathways of this toxicant, as shown by the immunosuppression of exposed animals, and the induction of the first stages of feminization in males, which corroborates that the synthetic estrogen acts as an endocrine disruptor. Such an intricate relationship is unprecedented and reinforces the importance of studying the serious consequences that multiple environmental stressors can cause to aquatic populations.

Delayed Consequences of Experimental Myocardial Infarction: Functional Responses to Stimulation of α2-Adrenoreceptors in the Isolated Heart.

We carried out a comparative analysis of the performance of the heart isolated from healthy rats and in 54 and 120 days after modeling of myocardium infarction. On day 120, the blood supply and heart contraction force increased, while HR did not change. Stimulation of α2-adrenoreceptors with clonidine hydrochloride (10-9 M) reduced the force and rate of contraction and the blood flow in the isolated heart from healthy rats. Stimulation of α2-adrenoreceptors of the isolated heart on day 54 after modeling of myocardium infarction induced a positive inotropic response, bradycardia, and insignificant changes in the heart blood flow. On day 120, stimulation of α2-adrenoreceptors slightly reduced HR and the force of contraction and induced biphasic changes in the coronary flow of the isolated heart.

Deletion of miRNA-22 Induces Cardiac Hypertrophy in Females but Attenuates Obesogenic Diet-Mediated Metabolic Disorders.

Obesity is a risk factor associated with cardiometabolic complications. Recently, we reported that miRNA-22 deletion attenuated high-fat diet-induced adiposity and prevented dyslipidemia without affecting cardiac hypertrophy in male mice. In this study, we examined the impact of miRNA-22 in obesogenic diet-induced cardiovascular and metabolic disorders in females. Wild type (WT) and miRNA-22 knockout (miRNA-22 KO) females were fed a control or an obesogenic diet. Body weight gain, adiposity, glucose tolerance, insulin tolerance, and plasma levels of total cholesterol and triglycerides were measured. Cardiac and white adipose tissue remodeling was assessed by histological analyses. Echocardiography was used to evaluate cardiac function and morphology. RNA-sequencing analysis was employed to characterize mRNA expression profiles in female hearts. Loss of miRNA-22 attenuated body weight gain, adiposity, and prevented obesogenic diet-induced insulin resistance and dyslipidemia in females. WT obese females developed cardiac hypertrophy. Interestingly, miRNA-22 KO females displayed cardiac hypertrophy without left ventricular dysfunction and myocardial fibrosis. Both miRNA-22 deletion and obesogenic diet changed mRNA expression profiles in female hearts. Enrichment analysis revealed that genes associated with regulation of the force of heart contraction, protein folding and fatty acid oxidation were enriched in hearts of WT obese females. In addition, genes related to thyroid hormone responses, heart growth and PI3K signaling were enriched in hearts of miRNA-22 KO females. Interestingly, miRNA-22 KO obese females exhibited reduced mRNA levels of Yap1, Egfr and Tgfbr1 compared to their respective controls. This study reveals that miRNA-22 deletion induces cardiac hypertrophy in females without affecting myocardial function. In addition, our findings suggest miRNA-22 as a potential therapeutic target to treat obesity-related metabolic disorders in females.

Defining Cardiac Dysautonomia - Different Types, Overlap Syndromes; Case-based Presentations.

The cardiovascular branch of autonomic nervous system (ANS) is responsible for the regulation of heart rate, blood pressure, and maintaining homeostasis during physiological stress such as exercise and standing upright. ANS constantly controls the rate and force of heart contractions and the vascular tone with the aim to maintain the sufficient tissue perfusion with oxygenated blood and secure venous return to the heart. Dysautonomias, result of ANS malfunction, are often found in patients with cardiovascular symptoms. Apart from the most prevalent one, arterial hypertension, the cardiovascular dysautonomic continuum encompasses other important although less known conditions: postural orthostatic tachycardia syndrome, inappropriate sinus tachycardia, orthostatic hypotension and reflex syncope. Moreover, heart diseases may evoke autonomic imbalance by themselves; cardiac pump failure is usually associated with sympathetic hyperactivity, neuroendocrine vasopressor activation, higher heart rate, reduced heart rate variability and baroreflex hyposensitivity, all of which are predictors of adverse outcomes. Cardiologists and electrophysiologist frequently see patients for the evaluation and management of unexplained syncope, orthostatic intolerance, heart rhythm abnormalities and symptoms of palpitations. Recognizing the presence of cardiac dysautonomia is an important skill which is necessary for the appropriate evaluation and treatment of these patients. Clinical presentations may overlap, and the importance of a thorough history cannot be over-emphasized. In this review we will present a cases of a patients with cardiac dysautonomia which is illustrative of a typical patient experience, followed by a review of the autonomic nervous system and discussion of prevalence, clinical presentation, and pathophysiology of common cardiac dysautonomias.

Transcriptomic response to elevated water temperatures in adult migrating Yukon River Chinook salmon (Oncorhynchus tshawytscha).

Chinook salmon (Oncorhynchus tshawytscha) declines are widespread and may be attributed, at least in part, to warming river temperatures. Water temperatures in the Yukon River and tributaries often exceed 18°C, a threshold commonly associated with heat stress and elevated mortality in Pacific salmon. Untangling the complex web of direct and indirect physiological effects of heat stress on salmon is difficult in a natural setting with innumerable system challenges but is necessary to increase our understanding of both lethal and sublethal impacts of heat stress on populations. The goal of this study was to characterize the cellular stress response in multiple Chinook salmon tissues after acute elevated temperature challenges. We conducted a controlled 4-hour temperature exposure (control, 18°C and 21°C) experiment on the bank of the Yukon River followed by gene expression (GE) profiling using a 3'-Tag-RNA-Seq protocol. The full transcriptome was analysed for 22 Chinook salmon in muscle, gill and liver tissue. Both the 21°C and 18°C treatments induced greater activity in genes associated with protein folding (e.g. HSP70, HSP90 mRNA) processes in all tissues. Global GE patterns indicate that transcriptomic responses to heat stress were highly tissue-specific, underscoring the importance of analyzing multiple tissues for determination of physiological effect. Primary superclusters (i.e. groupings of loosely related terms) of altered biological processes were identified in each tissue type, including regulation of DNA damage response (gill), regulation by host of viral transcription (liver) and regulation of the force of heart contraction (muscle) in the 21°C treatment. This study provides insight into mechanisms potentially affecting adult Chinook salmon as they encounter warm water during their spawning migration in the Yukon River and suggests that both basic and more specialized cellular functions may be disrupted.

Влияние блокады пейсмекерных токов на сердце крыс при формировании адренергической иннервации

Hyperpolarization-activated currents (If) contribute to the generation of spontaneous electrical activity in the heart. If are modulated by the cAMP level, sympathetic, and parasympathetic parts of the autonomic nervous system. The innervation development is an important factor in the formation of the ionic current orchestra in the cardiomyocytes. The age of 6 weeks in rats poses a particular interest, because at that point the heart rate is at its slowest, and the adrenergic innervation completes its development. The aim of thist study was to investigate the role of If current in the myocardial function regulation at one of the stages of sympathetic heart innervation development. The analysis of the results revealed that in the experiments on Langendorf-isolated heart the application of If blocker ZD 7288 in 10-9-10-5 M concentrations to rats of this age led to a decrease in the heart rate. ZD 7288 in 10-8-10-5 M concentrations reduced the left ventricular pressure and the coronary flow of the isolated heart in 6-week old rats. The perfusion of the isolated heart with If blocker in 10-9 M concentration increased the left ventricular pressure, but did not affect the coronary flow. In the studies of the atrial cardiomyocyte electrical activity, ZD7288 (10-7-10-5M) increased the action potential duration at the 50% and 90% repolarization level, and reduced the action potential generation frequency. Together, these results show that the If blockade affects the heart rate, heart contraction force, and coronary flow of the isolated heart of 6-week old rats. Apparently, the heart at the stage of completion of the adrenergic innervation development has a higher density of these currents than in adult rats, which manifests in a more pronounced response to the If blockade. The changes in the heart contraction force can be attributed to the changes in the repolarization phase duration of the working cardiomyocytes.

Predicting the physiological response of Tivela stultorum hearts with digoxin from cardiac parameters using artificial neural networks

Multi-layer perceptron artificial neural networks (MLP-ANNs) were used to predict the concentration of digoxin needed to obtain a cardio-activity of specific biophysical parameters in Tivela stultorum hearts. The inputs of the neural networks were the minimum and maximum values of heart contraction force, the time of ventricular filling, the volume used for dilution, heart rate and weight, volume, length and width of the heart, while the output was the digoxin concentration in dilution necessary to obtain a desired physiological response. ANNs were trained, validated and tested with the dataset of the in vivo experiment results. To select the optimal network, predictions for all the dataset for each configuration of ANNs were made, a maximum 5% relative error for the digoxin concentration was set and the diagnostic accuracy of the predictions made was evaluated. The double-layer perceptron had a barely higher performance than the single-layer perceptron; therefore, both had a good predictive ability. The double-layer perceptron was able to obtain the most accurate predictions of digoxin concentration required in the hearts of T. stultorum using MLP-ANNs.

PARTICIPATION OF TRPM4/TRPM7 CHANNELS IN THE CARDIAC ACTIVITIES OF CARVACROL ON ANIMALS WITH ESSENTIAL HYPERTENSION

IntroducionCarvacrol (CAR), a phenolic monoterpene, has been described to cause hypotension and bradychardia and in our study demonstrated a direct cardiac action of CAR in the contractility and force of isolated atria from spontaneously hypertensive (SHR) and normotensive controls rats (Wistar Kyoto ‐WKY). Then, the aim of this study it was to investigate the involvement of TRPM4 and TRPM7 channels in cardiac activities of CAR.MethodsMale SHR and WKY (250–300 g) were euthanized in CO2 chamber, and the left (LA) and right atria (RA) removed and isolated were maintained in a organ bath with krebs‐bicarbonate at a temperature of 37 ° C and aerated with a mixture carbogenic. The LA preparations were stimulated electrically continuously. The RA preparations were mounted in the same organ bath, but not were stimulated, allowing measures and rhythmicity of spontaneous contractions. The role of TRPM4 and TRPM7 in cardiac activities of CAR was investigated using channels blockers and molecular modeling tools (morphological similarity). All experimental protocols were approved by CEUA‐Animal use and care ethics committee‐ICS/UFBA (019/2011). Were considered significant values of p <0.05.ResultsIn studies with the isolated LA and RA, CAR 100μM induced significant negative chronotropic (CE) and inotropic effect (IE), respectively, in both WKY and SHR rats. To investigate the role of TRPM channels in these responses observed, TRPM4 [lanthanum 100μM (LAN), flufenamic acid 10μM (FF) and 9‐phenanthrol 10μM (9‐PHE)] and TRPM7 [magnesium 1.5mM (MG)] blockers were used. LAN, FF, 9‐PHE and MG significantly attenuated the negative CE of CAR 100μM in SHR, but not in WKY rats. However, MG significantly reduced heart automaticity in SHR and WKY rats in comparison to the control group. Interestingly, CAR in the presence of LAN, FF, 9‐PHE and MG significantly induced an additional negative IE in the SHR. Furthermore, these compounds, in the absence of CAR, reduced the cardiac contractile force in SHR in comparison to the control group. In WKY LA, the effect of CAR was changed only by 9‐PHE, but the heart contraction force was significantly reduced in the presence FF and 9‐PHE in the absence of the monoterpene. Additionally, CAR shows 86.62% chemical similarity to 9‐PHE, according to SURFLEX‐SIM software, and 9‐PHE and FF compounds have similar shape and electrostatic potential, as calculated in SYBYL®2.0, furthermore, there are data reporting that CAR inhibits TRPM7 channels in HEK cells (PARNAS et al.; 2009) and inhibits completely TRPM7 current input and output in human atrial myocytes (MACIANSKIENE et al, 2012).ConclusionsTaken together, these results suggest TRPM7 channel seems to influence heart rate and force of contraction, whereas TRPM4 channels influence in the force of contraction, at least at the atrial level. Further, CAR, along with magnesium, may act in a signaling pathway modified by hypertension. The in silico results are in good agreement with in vitro data and point out that CAR has all the chemical requirements to bind to TRPM4.Support or Funding InformationFundação de Amparo à Pesquisa do Estado da Bahia (FAPESB)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

BDNF modulates heart contraction force and long-term homeostasis through truncated TrkB.T1 receptor activation

BDNF modulates heart contraction force and long-term homeostasis through truncated TrkB.T1 receptor activation

Gene microarray analyses for potential biomarkers of single and recurrent venous thromboembolism.

Venous thromboembolism is a major cause of morbidity and mortality with a high recurrence rate. The present study aimed to explore the molecular mechanisms and potential biomarkers of single venous thromboembolism (SVTE) and recurrent venous thromboembolism (RVTE). The microarray dataset GSE19151 was downloaded from Gene Expression Omnibus, which contained data from whole blood samples from 63 healthy controls, 32 SVTE and 38 RVTE patients. Differentially expressed genes (DEGs) in the SVTE and RVTE groups compared with those in the controls were identified using the t-test, followed by clustering analysis of DEGs and samples. Functional and pathway enrichment analyses were performed for DEGs in patients with RVTE and SVTE, as well as specific DEGs in patients with RVTE. The identified 42 DEGs in RVTE were mainly enriched in biological processes of cellular protein metabolism, gene expression and translational elongation as well as in pathways associated with ribosomes, Parkinson's disease and oxidative phosphorylation. In SVTE, 20 DEGs were identified, which were mainly involved in biological processes of biopolymer biosynthesis, translational elongation and cellular protein metabolism as well as pathways associated with ribosomes and cardiac muscle contraction. In RVTE, 22 specific DEGs were mainly involved in translational elongation, negative regulation of the force of heart contraction by chemical signals, cell proliferation, ribosomal pathways and protein export. The identified DEGs of SVTE, including COX7C and UQCRQ, may be potential biomarkers for SVTE, and the specific DEGs of RVTE, including ADRBK1, NDUFA5 and ATP5O, may be potential biomarkers for RVTE.

BDNF modulates heart contraction force and long-term homeostasis through truncated TrkB.T1 receptor activation.

Brain-derived neurotrophic factor (BDNF) is critical for mammalian development and plasticity of neuronal circuitries affecting memory, mood, anxiety, pain sensitivity, and energy homeostasis. Here we report a novel unexpected role of BDNF in regulating the cardiac contraction force independent of the nervous system innervation. This function is mediated by the truncated TrkB.T1 receptor expressed in cardiomyocytes. Loss of TrkB.T1 in these cells impairs calcium signaling and causes cardiomyopathy. TrkB.T1 is activated by BDNF produced by cardiomyocytes, suggesting an autocrine/paracrine loop. These findings unveil a novel signaling mechanism in the heart that is activated by BDNF and provide evidence for a global role of this neurotrophin in the homeostasis of the organism by signaling through different TrkB receptor isoforms.

Dynamic Expression of MicroRNA-127 During Porcine Prenatal and Postnatal Skeletal Muscle Development

MicroRNAs (miRNAs), evolutionarily conserved non-coding RNAs in length 21-24 bp, play a critical role in skeletal muscle development. In this study, to explore the function of mircoRNA-127 in porcine skeletal muscle development, eight tissue samples from adult pigs and longissimus muscle samples at 26 developmental stages were collected from Tongcheng and Landrace pigs. The spatial-temporal expression profiles of miRNA-127 were carried out using step-loop quantitative real-time PCR (stem-loop RT-PCR). To explore the molecular functions of miRNA-127, we predicted its target genes and performed functional annotation using bioinformatics methods. Results suggested that miRNA-127 was abundantly expressed in heart, ovary, uterus and spleen tissues and was weakly expressed in liver, lung, kidney and small intestine in both Tongcheng and Landrace pigs. And miRNA-127 showed significant expression differences in heart, ovary, spleen and uterus tissues between these two breeds. miRNA-127 basically kept at a relatively stable high level in middle and later embryonic stages and a low expression level in early embryonic stages and postnatal stages, but the expression levels of miRNA-127 were higher in Tongcheng pigs than in Landrace at most developmental stages. miRNA-127 potentially regulated 240 candidate genes. Results of Gene Ontology and KEGG pathway analysis indicated that these genes could be involved in many molecular functions and mechanisms, such as regulation of the force of heart contraction, regulation of transcription, regulation of T cell differentiation, MAPK signaling pathway and GnRH signaling pathway. Many significantly enriched GO terms and KEGG pathways were related to skeletal muscle development. This study will be helpful to understand the biological function for miRNA-127 and identify candidate gene associated with meat production traits in pigs.

Modulation of Strain-Specific Differences in Gene Expression by Cannabinoid Type 2 Receptor Deficiency

Previous studies have shown that the skeletal consequences of cannabinoid receptor deficiency differ in different strains of mice. In order to explore the mechanisms responsible, we analysed global gene expression in bone from wild-type CD1 mice and littermates with targeted inactivation of the type 2 cannabinoid receptor (Cnr2 (-/-)) and compared the results with those obtained from a similar analysis of wild-type and Cnr2 (-/-) C57BL/6 mice. Trabecular bone volume was increased in Cnr2 (-/-) CD1 mice compared with wild-type littermates but decreased in Cnr2 (-/-) C57BL/6 mice. Microarray analysis identified 354 genes in which substantial differences in gene expression (>1.5-fold) were observed that were specifically affected by Cnr2 deficiency. Bioinformatic analysis of data from wild-type mice of each strain revealed Cnr2-dependent differences in expression of genes clustering within the gene ontology (GO) terms immune response (p < 0.0001), positive regulation of response to stimulus (p < 0.0001), nucleotide binding (p = 0.002), and ribonucleotide binding (p = 0.003). Bioinformatic analysis of data from Cnr2 (-/-) mice of each strain revealed associations between GO terms corresponding to the extracellular region (p = 0.002), the cell surface (p = 0.02), antigen binding (p = 0.03), external side of plasma membrane (p = 0.04), and regulation of the force of heart contraction (p = 0.04). We conclude that Cnr2 deficiency affects expression of a large number of genes in different strains of mice, and that these differences are likely to be responsible in part for the differences in skeletal phenotype that we and others have observed in mice with defective cannabinoid receptor signalling in different genetic backgrounds.

Motivation in psychocardiological rehabilitation

In this book a group of independed-minded academics has orchestrated a multi-authored text that represents an update of knowledge concerning how motivation influences Cardiovascular (CV) response. Discussing diverse motivational approaches that are representative of works carried out in several areas of psychology, health implications of the linkages between motivational variables and CV response have been investigated. The volume is divided into two major parts: Part I includes chapters that concern mechanisms of motivational influence on CV response, while in the Part II motivational paths to carry out with the aim of investigate CV response in different life circumstances have been considered. In more detail, 4 subsections organize Part I through 10 chapters, and 3 subsections constitute Part II by means of 9 chapters, each of those preceded by a summary of the key points. The opening chapters discuss the importance of modern neuroimaging techniques in allowing occasions to investigate how the interplay between CV status, cognitive-emotional functioning, and environmental demands are realized within the central and peripheral nervous systems. The relationship between emotional arousal and CV response has been noteworthy argued and enriched by results from recent research findings in various disciplines (Pietrabissa et al., 2012; Compare et al., 2013a). These studies demonstrate stress, motivational intensity, individual personality, self-regulation and mood states being in charge of health damaging CV adjustments, such as heart rate, blood pressure, and heart contraction force (Compare et al., 2011a, 2012, 2013b). Part II mainly contains evidences that CV activity is an indicator or even cause for CV diseases development, also including explanations about the role covered by gender, psychological processes, and social interactions in influencing health outcomes via relevant biological pathway. In addition, a set of considerations that may guide future research on this subject are discussed. Due to the various contributions from different authors of different countries, both style of writing and chapters arrangement widely varies. Some issues are effectively revisited on several occasions in the volume, constituting minor imperfections in an otherwise excellent, comprehensive, and up-to-date overview of mechanisms and applications related to CV disease. In fact, this book, edited by two psychologists and written by an International group of specialists in different fields of medicine, successfully covers the subject. Because of diseases generally display a multifactorial aetiology and symptoms require to be assumed as manifestations of a complex interplay of several factors, the bio-psycho-social approach of illness theorized by Engel (1977) remains in the background. Health and illness are not seen as opposite concepts or distinct entities but extremes of a continuum on which individuals constantly flux depending on the quality of their daily-life experiences, influenced by biological (e.g., genetics, age), psychological (e.g., attitude, stress) (Compare et al., 2011b, 2013c), and social (e.g., interpersonal relationships, socio-economic status) factors (Castelnuovo, 2010; Compare et al., 2013c). Due to this complexity, as well as stated the crucial role of both personal dispositions and intentions in modifying personal attitudes and behaviors, the relevance of setting realistic goal, implementing patient-centered treatments and developing motivational enhancement techniques, is highlighted. Overall, this book represents a well-collated collection of research outcomes, successfully demonstrating the importance of both psychological factors and motivation in the treatment of patients suffering from CV diseases (Manzoni et al., 2011a). In fact, as extensively discussed through the pages of this volume, the individual's level of initial motivation, reflecting the maximum energy spent by a person for goals attainment, represent one the main predictor of success in preventing and managing CV risk factors (Manzoni et al., 2011b) also by modern telecare systems (Villani et al., 2007). However, the text is so densely written than chapters seem to be resources for references rather than flowing text. Despite recent technological changes have made information readily available on the Internet, because of potentially appealing scholars and practitioners from a wide range of areas, together with its acceptable price, this book still constitute a significant source of outcomes and data.

Very important pharmacogene summary ADRB2

The beta2-adrenergic receptor (beta2-AR) is a member of the G-protein-coupled adrenergic receptor family with seven transmembrane segments. Similar to other members of this receptor family, beta2-AR specifically binds and is activated by the endogenous class of ligands known as catecholamines, and epinephrine in particular. The gene encoding this receptor, ADRB2, was cloned by Kobilka et al. in 1987 and is localized to chromosome 5q31–q32, a region that has been linked with asthma and asthma related phenotypes [1,2]. ADRB2 consists of a single exon of 2015 nucleotides, which encodes a 413 amino acid protein. This review highlights the genetic polymorphisms in ADRB2 and the pivotal role of beta2- AR in the regulation of the cardiac, pulmonary, vascular, endocrine, and central nervous systems. ADRB2 is abundantly expressed in bronchial smooth muscle cells and activation of the resulting receptor leads to bronchodilation. In addition, this gene is expressed in cardiac myocytes and vascular smooth muscle cells. Activation of beta2-AR in these cells causes an increase in the rate and force of heart contractions. Intracellular signaling upon beta2-AR activation is largely affected through a trimer of G proteins coupled to adenylate cyclase, to produce cyclic adenosine monophosphate. This, in turn, activates protein kinase A, leading to the phosphorylation and down-regulation of proteins including beta2-AR itself (please refer to PharmGKB β-agonist and β-blocker Pathway for further details: https://www.pharmgkb.org/do/serve?objId=PA2024&objCls=Pathway#). Beta2-AR is the target of clinically important drugs for asthma and cardiovascular conditions including hypertension and congestive heart failure (CHF). Beta-receptor agonists (e.g. albuterol, salmeterol) and antagonists (e.g. carvedilol and propranolol) are among the most commonly prescribed medications in the treatment of asthma and cardiovascular disease, respectively. Although some beta-blockers are ‘selective’ for the beta1-AR (e.g. metoprolol and atenolol), these also antagonize the beta2-AR at higher concentrations. A number of genetic polymorphisms in the ADRB2 gene have been described which affect gene expression, the function of the resulting receptor, and response to beta2-agonists.

Synthesis, structural characterization and ex vivo biological properties of a new complex [Cu(propranolol) 2]·2H 2O, a potential beta-blocker

The synthesis and spectroscopic characterization (UV–Vis, IR, EPR) of a new copper complex with a beta-blocker propranolol (1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol) are presented. Besides, the X-ray crystal structure of [Cu(propranolol) 2]·2H 2O is determined, showing two different copper ions, one coordinated through two S propranolol isomers and the other through two R isomers. The effect on the heart contraction force and on the heart rate plus the block of response to adrenaline of the complex and the free ligand, were studied. The effect of [Cu(propranolol) 2]·2H 2O on contractility was very similar to that of the free propranolol while the reduction on the heart rate is approximately 30% of the reduction obtained with the free ligand. This is an encouraging result since the search of new beta-blocker drugs that have lesser effect on heart rate is one of the important topics in cardiac pharmacology. The block of the response to adrenaline is at least similar for both ligand and complex.

Cocaine‐ and amphetamine‐regulated transcript (CART) peptide as an in vivo regulator of cardiac function in Rana ridibunda frog

The aim of this study was to investigate the effect of CART peptide on cardiac performance and on the physiological signalling pathways involved using Rana ridibunda frog heart preparations in vivo. The CART peptide, when injected into the venous sinus, significantly and reproducibly increased the force of frog heart contractions by up to 33.0 +/- 6.4% during the first 15 min after its application but did not influence the chronotropic activity of the frog heart. The positive inotropic effect was entirely blocked by prazosin, pertussis toxin, R(p)-adenosine 3',5'-cyclic monophosphorothioate, autosauvagine 30 or metyrapone, as well as by extirpation of the pituitary gland, functional elimination of the inter-renal glands and long-lasting starvation, and was not observed on isolated heart preparations. Propranolol and double pithing were without significant effect on this phenomenon. It was concluded that: (i) CART peptide, administered to frogs in vivo, increases the force of heart contractions; (ii) this effect of the peptide is exerted via activation of the hypothalamic-pituitary-inter-renal gland axis through a corticoliberin-sensitive mechanism; (iii) CART augments the pumping function of the heart via a corticosteroid-dependent potentiation of myocardial alpha(1)-adrenoreceptors signalling; and (iv) prolonged food deprivation abolishes the positive inotropic effect of CART, suggesting the participation of endogenous CART in the physiological adaptation of the circulatory system to limitations of energy consumption.

Cardiovascular properties of aqueous extract from &lt;i&gt;Tapinanthus dodoneifolius&lt;/i&gt; DC Danser

Aqueous extracts of Tapinanthus dodoneifolius DC Danser. (Loranthaceae) (AETD) were investigated for cardiovascular activities on isolated rat aorta and heart. AETD did not affect heart rate but significantly enhanced heart contraction force and relaxation capacity. AETD (0.001-1mg/ml) elicited a dose-dependent relaxation on arteries which was previously contracted with phenylephrine [10-6M] (rat aorta). AETD induces relaxation in endothelium dependent manner. When Indomethacin failed to inhibit AETD vasodilatory activity, in the presence of L-NAME, the vasodilatory activity of AETD was completely abolished. These results suggest a cardiotropic activity without any tachycardia as a side effect for AETD. However, AETD elicited vasodilatory activity which involved NO from endothelium. Key words : Tapinanthus dodoneifolius, endothelium , vasodilator , rat. Afr. J. Trad. Comp. Alt. Med. , 2005, 2 (1): 25-30