The impact of alpha1-adrenoceptors up-regulation accompanied by the impairment of beta-adrenergic vasodilatation in hypertension
9 pages, 7 figures, 3 tables.-- PMID: 19060223 [PubMed]
Myocardial and Peripheral Lymphocytic Transcriptomic Dissociation of β-adrenoceptors and G Protein–coupled Receptor Kinases in Heart Transplantation
Background The genetic expression of adrenergic receptors plays an important pathophysiologic role in heart failure. G protein–coupled receptor kinases (GRKs) desensitize the β-receptor to catecholaminergic stimulation. It has been suggested that their mRNA expression in peripheral lymphocytes could mirror the changes in their myocardial expression in the failing heart, but this relationship between the myocyte and lymphocyte has not been studied in heart transplantation (HT). The objective of this study was to analyze adrenergic receptor and GRK mRNA expression in myocardium and lymphocytes and their correlation. Methods Twenty-three HT patients without evidence of acute rejection or echoc…
Myocardial and lymphocytic expression of eNOS and nNOS before and after heart transplantation: Relationship to clinical status
Abstract Aims The present study investigates the expression and clinical relevance of the constitutive NO synthases in heart and peripheral blood mononuclear cells (PBMCs) obtained from heart failure patients. Main methods mRNA and protein levels (qRT-PCR and immunoblot) of eNOS and nNOS were determined in: i) Left ventricle (LV, n = 4) and PBMCs (n = 10) from healthy donors; ii) LV, right ventricle (RV) and PBMCs of heart failure (HF) patients (n = 32); and iii) biopsies and PBMCs of the HF patients after cardiac transplant (n = 15). Key findings Expression of constitutive NOS isoforms in heart exhibits wide variability in HF patients, but this variability was not related to aetiology, dis…
Changes in Adrenoceptors and G-Protein-Coupled Receptor Kinase 2 in <smlcap>L</smlcap>-NAME-Induced Hypertension Compared to Spontaneous Hypertension in Rats
This work compares the expression of adrenoceptors (ARs) and G-protein-coupled receptor kinase (GRK) 2 (RT-PCR and immunoblotting) and functional responses in conductance (aorta) and resistance vessels (mesenteric resistance arteries; MRA) in two different models of rat hypertension: hypertension induced by chronic treatment with <smlcap>L</smlcap>-NAME (N<sup>G</sup>-nitro-<smlcap>L</smlcap>-arginine methyl-ester) (<smlcap>L</smlcap>-NAME-treated rats; LNHR), and genetically induced hypertension (spontaneously hypertensive rats; SHR). Changes found in the aorta, but not in the MRA, were: (1) a loss of contractile capacity, more evidently in α…
Beta-blockers: Historical Perspective and Mechanisms of Action
Beta-blockers are widely used molecules that are able to antagonize β-adrenergic receptors (ARs), which belong to the G protein-coupled receptor family and receive their stimulus from endogenous catecholamines. Upon β-AR stimulation, numerous intracellular cascades are activated, ultimately leading to cardiac contraction or vascular dilation, depending on the relevant subtype and their location. Three subtypes have been described that are differentially expressed in the body (β1-, β2- and β3-ARs), β1 being the most abundant subtype in the heart. Since their discovery, β-ARs have become an important target to fight cardiovascular disease. In fact, since their discovery by James Black in the …
Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure etiology and correlates to clinical variables.
Downregulation of β1- adrenergic receptors (β1-ARs) and increased expression/function of G-protein-coupled receptor kinase 2 (GRK2) have been observed in human heart failure, but changes in expression of other ARs and GRKs have not been established. Another unresolved question is the incidence of these compensatory mechanisms depending on heart failure etiology and treatment. To analyze these questions, we quantified the mRNA/protein expressions of six ARs (α1A, α1B, α1D, β1, β2, and β3) and three GRKs (GRK2, GRK3, and GRK5) in left (LV) and right ventricle (RV) from four donors, 10 patients with ischemic cardiomyopathy (IC), 14 patients with dilated cardiomyopathy (DC), and 10 patients wit…
Changes in the expression of α 1B -adrenoceptor in peripheral mononuclear cells correlates with blood pressure and plasmatic homocysteine
Human peripheral mononuclear cells (HPMC) have been suggested as a practical surrogate for myocardial or vascular cells. Present work analyses if changes in the expression of α1-adrenoceptors (ARs) in HPMC are related to the hypertensive state and its clinical consequences. Quantitative RT-PCR was employed to evaluate the mRNA levels of the three α1-ARs (α1A, α1B, α1D) in HPMC isolated from normotensive and hypertensive patients, and also in tissues from two animal models of hypertension: spontaneously hypertensive rats (SHR) and hypertension induced by chronic treatment with L-NAME. In patients, 24-h ambulatory blood pressure and serum biochemical profile were also recorded. We found that …
Changes in Adrenoceptor and GRK Expression in Patients With Chronic Pulmonary Regurgitation.
INTRODUCTION AND OBJECTIVES Pulmonary regurgitation (PR) is a frequent complication after repair of congenital heart disease. Lymphocyte expression of adrenoceptors (β1 and β2) and kinases (GRK2, GRK3, and GRK5) reflects the neurohumoral changes that occur in heart failure (HF). The main objective of this study was to describe the gene expression of these molecules in circulating lymphocytes in patients with severe PR. METHODS A prospective study was conducted to analyze lymphocyte expression of these molecules in patients with severe PR and compare it with expression in healthy controls and patients with advanced HF. RESULTS We studied 35 patients with severe PR, 22 healthy controls, and 1…
Beta-3 adrenergic receptor overexpression reverses aortic stenosis-induced heart failure and restores balanced mitochondrial dynamics
25 p.-7 fig.
β2- and β1-Adrenoceptor Expression Exhibits a Common Regulatory Pattern With GRK2 and GRK5 in Human and Animal Models of Cardiovascular Diseases.
To explore if genic expression of β(1)- or β(2)-adrenoceptors (ARs) exhibits a common regulatory pattern with G protein-coupled receptor kinase (GRK) 2, GRK3, or GRK5 expression, we determined messenger RNA levels for these genes in different tissues from human and animal models of cardiovascular disease. We measured genic expression by qRT polymerase chain reaction in the left and right ventricles or peripheral blood mononuclear cells from healthy (n = 21), hypertensive (n = 20), heart failure (n = 24), and heart transplanted patients (n = 17) or in left ventricle, peripheral blood mononuclear cells, and kidney from spontaneously hypertensive rats or L-N-methyl-arginine-induced hypertensiv…
α1-Adrenoceptors in the rat cerebral cortex: New insights into the characterization of α1L- and α1D-adrenoceptors
36 p., figuras y tablas, bibliografía
beta-Adrenoceptor and GRK3 expression in human lymphocytes is related to blood pressure and urinary albumin excretion.
31 p., figuras, abreviaturas y bibliografía
Myocardial G Protein Receptor–Coupled Kinase Expression Correlates With Functional Parameters and Clinical Severity in Advanced Heart Failure
In heart failure (HF), sympathetic hyperactivation induces deleterious effects in myocardial β-adrenergic signaling, with receptor down-regulation and desensitization mediated by G protein receptor-coupled kinases (GRKs). We hypothesised that changes in GRK isoforms may be associated with clinical status in advanced HF, using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale.We included 31 patients with advanced HF undergoing transplantation. According to INTERMACS profiles, mRNA and protein levels of GRK isoforms in left ventricular (LV) myocardium were analyzed and compared with nonfailing LV samples.In failing LV myocardium, GRK2 and GRK5 (but not G…
Cambios en la expresión de adrenoceptores y GRK en pacientes con insuficiencia pulmonar valvular crónica
Resumen Introduccion y objetivos La insuficiencia pulmonar (IP) es una complicacion frecuente tras la intervencion de cardiopatias congenitas. La expresion en leucocitos mononucleares circulantes (LMC) de los adrenoceptores (β1 y β2) y de las cinasas (GRK2, GRK3 y GRK5) refleja los cambios neurohumorales que se producen en la insuficiencia cardiaca (IC). El objetivo principal es describir la expresion genica de dichas moleculas en LMC de pacientes con IP grave. Metodos Estudio prospectivo que analizo la expresion de las moleculas descritas en LMC de pacientes con IP grave en comparacion con controles sanos y pacientes con IC avanzada. Resultados Se estudio a 35 pacientes con IP grave, 22 co…
Increased endothelin-1 vasoconstriction in mesenteric resistance arteries after superior mesenteric ischaemia-reperfusion
BACKGROUND AND PURPOSE Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia-reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET-1. EXPERIMENTAL APPROACH SMA from male Sprague-Dawley rats was occluded (90 min) and following reperfusion (24 h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O2•−) production and ET-1 plasma concentration were evaluated by immunofluorescence, real-time quantitative PCR,…
Bloqueadores beta: perspectiva histórica y mecanismos de acción
Resumen Los bloqueadores beta son moleculas ampliamente utilizadas y capaces de antagonizar los receptores adrenergicos (RA) beta, pertenecen a la familia de receptores acoplados a proteinas G y reciben el estimulo de las catecolaminas endogenas. Tras su estimulacion, se activan cascadas intracelulares que en ultima instancia originan la contraccion cardiaca o la dilatacion vascular, segun el subtipo y su ubicacion. Se han descrito 3 subtipos, que se expresan de manera diferenciada en el organismo (RA-β1, β2 y β3), y el subtipo β1 es el mas abundante en el corazon. Desde su descubrimiento, los RA-β se han convertido en diana para combatir las enfermedades cardiovasculares. Desde su invencio…