Browsing by Author "Araos, Patricio"

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    Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall
    (2016) Araos, Patricio; Mondaca, David; Jalil Milad, Jorge; Yañez, Cristián; Novoa, Ulises; Mora, Italo; Ocaranza, María Paz
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    Early Changes in Cardiac Macrophage Subsets in Heart Failure with Preserved Ejection Fraction
    (2025) Gutiérrez Cisternas, Danae Abigail; Cordero Fernández, Karina Alejandra; Sepúlveda Sarmiento, Ruth Angélica; Venegas, Camilo; Altamirano, Diego; Candia, Camila; Ramírez Rojas, Gigliola; Araos, Patricio; Amador, Cristian A.; Hermoso, Marcela A.; Gabrielli Nervi, Luigi Arnaldo; Jalil Milad, Jorge Emilio; Ocaranza Jeraldino, María Paz
    Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by left ventricular diastolic dysfunction, exercise intolerance, low-grade chronic inflammation, and comorbidities such as hypertension, obesity, and glucose intolerance. Myocardial infiltration by activated macrophages has been proposed as a mechanism linking low-grade inflammation to increased diastolic LV stiffness in HFpEF. Changes in the relative abundance of cardiac macrophage populations may precede and promote the development of HFpEF in the aged heart. This study aimed to characterize the cardiac macrophage subsets that predominate during progression from experimental preclinical to established HFpEF. To generate the model, wild-type male C57BL/6N mice were randomized to control chow or a combination of high-fat diet plus L-NAME in drinking water for 5 weeks (asymptomatic pre-HFpEF) or 15 weeks (established HFpEF). At the end of each period, we measured body weight, running distance, metabolic biomarkers, systolic and diastolic blood pressure, myocardial function and morphology, cardiac remodeling by hypertrophic markers, morphometric analyses, fibrosis, cytokines TNF-α and IL-10, cardiac macrophage phenotype profiles (CCR2+ and CCR2−), and AMP-Activated Protein Kinase (AMPK)activity.Significant changes in myocardial macrophage populations were observed at 5 weeks (pre-HFpEF), specifically a decrease in resident reparative CCR2−MHCII− and increase in proinflammatory CCR2+MHCII+ macrophages. These early changes were associated with higher circulating TNF-α, decreased myocardial AMPK activation, and more severe myocardial fibrosis. At 15 weeks (established HFpEF), proinflammatory CCR2+MHCII+ macrophage levels remained elevated in the myocardium; whereas the initial number of resident reparative CCR2−MHCII- levels was reduced, it subsequently returned to baseline. In this model of HFpEF induced by a high-fat diet and L-NAME, which produced obesity, glucose intolerance, and hypertension, myocardial resident reparative CCR2−MHCII− macrophages decreased and proinflammatory CCR2+MHCII+ macrophages increased during preclinical stages. These early changes in cardiac macrophage profile were associated with low-grade inflammation and myocardial remodeling and preceded the onset of HFpEF.
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    Espironolactona aumenta los niveles circulantes de angiotensina-(1-9) y revierte el remodelado cardíaco en la hipertensión arterial experimental
    (2017) Ocaranza, María Paz; Moya, Jackeline; Araos, Patricio; Mondaca, David; Jalil Milad, Jorge
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    Improving Amphetamine Therapeutic Selectivity: N,N-dimethyl-MTA has Dopaminergic Effects and does not Produce Aortic Contraction
    (2014) Sotomayor-Zarate, Ramon; Jara, Pablo; Araos, Patricio; Vinet, Raul; Quiroz, Gabriel; Renard, Georgina M.; Espinosa, Pedro; Hurtado-Guzman, Claudio; Moya, Pablo R.; Iturriaga-Vasquez, Patricio; Gysling, Katia; Reyes-Parada, Miguel
    Amphetamine derivatives have therapeutic potential in diseases such as attention deficit hyperactivity disorder, narcolepsy and obesity. However, their prolonged use has been associated with cardiovascular toxicity and addiction. In recent years, we have studied the pharmacological effects of amphetamine derivatives such as methylthioamphetamine (MTA) and N,N-dimethyl-thioamphetamine, with the aim of improving their therapeutic selectivity. In this work, we show that similarly to MTA, N,N-dimethyl-thioamphetamine has effects on the dopamine system, producing a significant increase in extracellular levels of dopamine (as measured by in vivo brain microdialysis) and locomotor activity, which is a behavioural measure of dopaminergic activation. However, unlike MTA, N,N-dimethyl- thioamphetamine does not produce aortic contraction in vitro. Our results show that N,N-dimethyl-thioamphetamine is a drug that retains the dopaminergic effects of amphetamine derivatives but exhibits a lower potential for producing cardiovascular side effects.