Cardiac mineralocorticoid receptor and the Na+/H+ exchanger: Spilling the beans.

Current evidence reveals that cardiac mineralocorticoid receptor (MR) activation following myocardial stretch plays an important physiological role in adapting developed force to sudden changes in hemodynamic conditions. Its underlying mechanism involves a previously unknown nongenomic effect of the MR that triggers redox-mediated Na+/H+ exchanger (NHE1) activation, intracellular Na+ accumulation, and a consequent increase in Ca2+ transient amplitude through reverse Na+/Ca2+ exchange. However, clinical evidence assigns a detrimental role to MR activation in the pathogenesis of severe cardiac diseases such as congestive heart failure. This mini review is meant to present and briefly discuss some recent discoveries about locally triggered cardiac MR signals with the objective of shedding some light on its physiological but potentially pathological consequences in the heart.Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentin

Cardiac Mineralocorticoid Receptor and the Na+/H+ Exchanger: Spilling the Beans

Current evidence reveals that cardiac mineralocorticoid receptor (MR) activation following myocardial stretch plays an important physiological role in adapting developed force to sudden changes in hemodynamic conditions. Its underlying mechanism involves a previously unknown nongenomic effect of the MR that triggers redox-mediated Na+/H+ exchanger (NHE1) activation, intracellular Na+ accumulation, and a consequent increase in Ca2+ transient amplitude through reverse Na+/Ca2+ exchange. However, clinical evidence assigns a detrimental role to MR activation in the pathogenesis of severe cardiac diseases such as congestive heart failure. This mini review is meant to present and briefly discuss some recent discoveries about locally triggered cardiac MR signals with the objective of shedding some light on its physiological but potentially pathological consequences in the heart.Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentin

Silencing of the Na+/H+ exchanger 1(NHE-1) prevents cardiac structural and functional remodeling induced by angiotensin II

Chronic activation of the renin angiotensin system (RAS) favors several cardiac diseases, among which myocardial hypertrophy occupies an outstanding place. In this context, the hyperactivity of the cardiac Na+/H+ (NHE-1) exchanger plays a key role. The pathologic remodeling of the myocardium constitutes an independent risk factor for morbidity and mortality with continuously increasing healthcare cost. Therefore, the development of better therapeutic strategies emerges as highly mandatory. Our goal was to prevent angiotensin II (ANGII)-induced cardiac hypertrophy by NHE-1 gene silencing in Wistar rats. The intramyocardial injection of a lentivirus coding a specific small interference RNA (l-shNHE1) significantly reduced NHE-1 expression exclusively in the heart (~ 50 %) and prevented cardiac remodeling in rats exposed to chronic infusion of ANG II (heart weigh/tibia length: 24,03 ± 0,7915 mg/mm vs 28,45 ± 0,9779 mg/mm and collagen volume fraction 2,526 ± 0,5003 vs 5,982 ± 1,043 in l-shNHE1 + ANGII and ANGII, respectively).Interestingly, this was accompanied by an improvement in cardiac function determined by echocardiography even though blood pressure remained elevated (Fractional shortening 0,5960 ± 0,4228 vs -0,9567± 0,06888 and blood pressure at the end of ANGII treatment 141,2 ± 6,117 mm Hg vs 134,1 ± 6,723 mm Hg ; in l-shNHE1 + ANGII and ANGII, respectively). ANGII infusion increased myocardial NADPH oxidase activity but the l-shNHE1 injection prevented oxidative stressas revealed by the normalization of lipid peroxidation (T-BARS 12,40 ± 2,887.vs 23,05 ± 1,537 in lshNHE1 + ANGII and ANGII, respectively). These results allow as to propose the partial silencing of the cardiac NHE-1 through lentiviralinjection as a promising tool in the prevention of ANGII-induced cardiac hypertrophy.Fil: Medina, Andrés Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Pinilla, Oscar Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Caldiz, Claudia Irma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentin

Gender differences in cardiac left ventricular mass and function: clinical and experimental observations

Background: The aim of this study was to evaluate gender-associated impact on left ventricular mass (LVM) and on left ventricular function (LVF) in humans and rats with aging. Methods: Myocyte area and collagen volume fraction (CVF) were studied in rats. LVM and LVF were evaluated in animals and humans by echocardiography and LVM index (LVMI) was obtained. Results: LVMI, myocyte area and CVF were similar in males and females of 1-month-old rats. LVMI in children was similar in both genders. In contrast, in 6-month-old rats (5 males and 5 females), LVMI (17.7 ± 0.7 mg/mm vs. 10.1 ± 0.2 mg/mm; p < 0.01), and myocyte area (4572.5 ± 72.6 μm2 vs. 3293.85 ± 57.8 μm2 , p < 0.01) were higher in male animals without differences in CVF. Men (n = 25) exhibited greater LVMI than women (n = 25) (77.4 ± 3.2 g/m2 vs. 63.3 ± 1.8 g/m2 , p < 0.01), whereas the LVF was higher in women (105.9 ± 2.9% vs. 95.3 ± 3.5%, p < 0.01). Conclusions: There is a clear gender-associated impact on LVM with aging in humans and rats. Similar CVF and LVF associated to greater myocyte size and LVM in male rats suggest a process of physiological response. However, the increase in cardiac mass without an associated improved cardiac function in men in comparison to women could likely represent a potential disadvantage in the adaptive response during growth. (Cardiol J 2014; 21, 1: x–x)Fil: Escudero, Eduardo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Orlowski, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Diaz, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Pinilla, Oscar Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentin

Why the hypertensive patient develops heart failure?

La hipertensión arterial implica una situación de sobrecarga hemodinámica para el miocardio. El corazón responde aumentando su masa y dando lugar al desarrollo de hipertrofia cardíaca patológica. Ésta es una entidad que se caracteriza por aumento de la fibrosis intersticial, disminución de la densidad vascular, aumento de la apoptosis, re expresión del patrón génico fetal y deterioro de la contractilidad. Este remodelado estructural irreversible conlleva un aumento del riego cardiovascular, evolucionando muy frecuentemente hacia la insuficiencia cardíaca y muerte. Numerosas evidencias sustentan el papel protagónico en la fisiopatología de la hipertrofia cardíaca hipertensiva del intercambiador Na+/H+ cardíaco (NHE-1). El estiramiento miocárdico que resulta de la carga hemodinámica impuesta por la hipertensión arterial induce la hiperactividad del NHE-1 por un mecanismo autócrino/parácrino que involucra al sistema renina-angiotensina-aldosterona, entre otros actores. La consecuencia de la mayor actividad del NHE-1 es el aumento de la concentración intracelular de sodio y calcio y la activación de la vía prohipertrófica patológica calcineurina/NFAT. Evidencias recientes sustentan que el entrenamiento físico sostenido y el aumento de su principal efector humoral, el factor de crecimiento similar a insulina 1, son capaces de evitar la hiperactividad del NHE-1 permitiendo el desarrollo del remodelado miocárdico fisiológico con mejoría de la función contráctil.High blood pressure increases the hemodynamic load to the heart inducing the development of pathological cardiac hypertrophy. This entity is characterized by myocardial fibrosis, decreased myocardial vascular density, increased apoptosis, re-expression of fetal genes and cardiac dysfunction. It implies higher cardiovascular risk usually evolving to heart failure and cardiac death. Great amount of evidence supports that a key role of the cardiac Na+/H+ exchanger (NHE-1) in the pathophysiology of pathologic of hypertensive cardiac hypertrophy. Myocardial stretch due to hypertension triggers an autocrine/paracrine signaling cascade involving the renin-angiotensinaldosterone system that stimulates NHE-1 activity increasing intrecellular sodium and calcium. This favors calcineurin/NFAT activity and pathologic remodeling of the heart. Interestingly, it was recently proposed that training and insulin like growth factor 1 prevent NHE-1 hyperactivity allowing physiological remodeling in response to hemodynamic overload.Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Yeves, Alejandra del Milagro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentin

Endothelin isoforms and the response to myocardial stretch

Myocardial stretch elicits a biphasic increase in developed force with a first rapid force response and a second slow force response (SFR). The rapid phase is due to an increase in myofilament Ca(2+) responsiveness; the SFR, analyzed here, is ascribed to a progressive increase in Ca(2+) transients. Experiments were performed in cat papillary muscles to further elucidate the signaling pathway underlying the SFR. Although the SFR was diminished by BQ-123, a similar endothelin (ET)-1-induced increase in force was not affected: 23 +/- 2 vs. 23 +/- 3% (not significant). Instead, BQ-123 suppressed the contractile effects of ET-2 or ET-3 (21 +/- 2 and 25 +/- 3% vs. -1 +/- 1 and -7 +/- 3% respectively, P < 0.05), suggesting that ET-2 or ET-3, but not ET-1, was involved in the SFR. Each isoform activated the Na(+)/H(+) exchanger (NHE-1), increasing intracellular Na(+) concentration by 2.0 +/- 0.1, 2.3 +/- 0.1, and 2.1 +/- 0.4 mmol/l for ET-1, ET-2, and ET-3, respectively (P < 0.05). The NHE-1 inhibitor HOE-642 prevented the increases in force and intracellular Na(+) concentration induced by all the ET isoforms, but only ET-2 and ET-3 effects were sensitive to BQ-123. Real-time RT-PCR measurements of prepro-ET-1, -ET-2, and -ET-3 were performed before and 5, 15, and 30 min after stretch. No changes in ET-1 or ET-2, but an increase of approximately 60% in ET-3, mRNA after 15 min of stretch were detected. Stretch-induced ET-3 mRNA upregulation and its mechanical counterpart were suppressed by AT(1) receptor blockade with losartan. These data suggest a role for AT(1)-mediated ET-3 released in the early activation of NHE-1 that follows myocardial stretch.Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Garciarena, Carolina Denis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Dulce, Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Camilion, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentin

Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity

Aim: Myocardial Na+/H+ exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF-1—key humoral mediator of exercise training—inhibits myocardial NHE-1, at least in normotensive rats. Therefore, we hypothesize that IGF-1 by hampering NHE-1 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR. Methods: NHE-1 activity [proton efflux (JH+) mmol L−1 min−1], expression and phosphorylation; H2O2 production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence/absence of IGF-1. Results: IGF-1 significantly decreased NHE-1 activity (JH+ at pHi 6.95: 1.39 ± 0.32, n = 9 vs C 3.27 ± 0.3, n = 20, P <.05); effect prevented by AG1024, an antagonist of IGF-1 receptor (2.7 ± 0.4, n = 7); by the PI3K inhibitor wortmannin (3.14 ± 0.41, n = 7); and the AKT inhibitor MK2206 (3.37 ± 0.43, n = 14). Moreover, IGF-1 exerted an antioxidant effect revealed by a significant reduction in H2O2 production accompanied by an increase in SOD activity. In addition, IGF-1 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients. Conclusion: IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players.Fil: Yeves, Alejandra del Milagro. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); ArgentinaFil: Burgos, Juan Ignacio. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); ArgentinaFil: Caicedo Medina, Julian Alberto. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); ArgentinaFil: Villa-Abrille, María Celeste. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); ArgentinaFil: Ennis, Irene Lucia. Centro de Investigaciones Cardiovasculares (conicet- Universidad Nacional de la Plata); Argentin

The RAAS and SARS-CoV-2: A riddle to solve

El 31 de diciembre de 2019 se reportó el primer caso de COVID-19 en Wuhan, China, y desde entonces ha habido un interés creciente y sin precedentes por conocer todos los aspectos vinculados con esta nueva enfermedad. Uno de los temas que ha generado debate se vincula con la asociación entre la terapia antihipertensiva con inhibidores del sistema renina-angiotensina-aldosterona y la infección por el virus SARS-CoV-2. Si bien muchas preguntas siguen hoy en día sin poder ser respondidas, la intención de este comunicado es informar a los profesionales de la salud acerca del estado actual de conocimiento. Dado que este es un tema en constante evolución, se recomienda su actualización a medida que se presenten nuevas evidencias. A continuación daremos revisión a los estudios preclínicos y clínicos que relacionan el coronavirus con el sistema renina-angiotensina-aldosterona.The first case of COVID-19 was reported on 31 December 2019 in Wuhan, China. Ever since there has been unprecedented and growing interest in learning about all aspects of this new disease. Debate has been generated as to the association between antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors and SARS-CoV-2 infection. While many questions as yet remain unanswered, the aim of this report is to inform health professionals about the current state of knowledge. Because this is an ever-evolving topic, the recommendation is that it be updated as new evidence becomes available. Below, we provide a review of pre-clinical and clinical studies that link coronavirus to the RAAS.Fil: Choi, Marcelo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Villa-Abrille, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentin

May Measurement Month 2019: An analysis of blood pressure screening results from Argentina

The Argentinean Society of Hypertension, in agreement with the May Measurement Month (MMM) initiative of the International Society of Hypertension, implemented for the third consecutive year a hypertension screening campaign. A volunteer cross-sectional survey was carried out in public spaces and health centres during the month of May 2019 across 33 cities in Argentina. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg and/or diastolic BP ≥90 mmHg based on the mean of the second and third BP measurements, or in those on treatment for high BP. A total of 94 523 individuals (53.9 ± 17.8 years old, 55 231women and 39 292 men), were evaluated. The age and sex standardized mean BP was 124.7/77.2 mmHg. Among participants, 34.7% were overweight (25-29.9 m/kg2) and 28.7% had obesity (≥30 m/kg2). Individuals identified as being overweight had BP 3/2 mmHg higher and individuals with obesity 6/4 mmHg higher than those with normal weight. The prevalence of hypertension was 52.5%. Although 81.1% were aware and 77.7% were on antihypertensive treatment, only 46.0% of all individuals with hypertension had their BP controlled. Moreover, 19.8% of those not on any antihypertensive medication were found with raised BP. The low level of control of hypertension generates the critical need for the development of community-based prevention strategies reinforcing strategies to increase the awareness and control of hypertension.Fil: Salazar, Martin Rogelio Enrique. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Garcia Vazquez, Fortunato. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Espeche, Walter. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Marquez, Diego. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Becerra, Pedro. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Martinez Marissi, Evangelina. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Sorasio, Viviana B.. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Staffieri, Gustavo J.. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Kalbermatter, Arnoldo. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: De Cerchio, Alejandro E.. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Beaney, Thomas. Imperial College London; Reino UnidoFil: Partington, Giles. Imperial College London; Reino UnidoFil: Poulter, Neil R.. Imperial College London; Reino UnidoFil: Marín, Marcos. Sociedad Argentina de Hipertensión Arterial; ArgentinaFil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Sociedad Argentina de Hipertensión Arterial; Argentin

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements