Reduction of daily-use parabens and phthalates reverses accumulation of cancer-associated phenotypes within disease-free breast tissue of study subjects.

Estrogenic overstimulation is carcinogenic to the human breast. Personal care products (PCPs) commonly contain xenoestrogens (XE), such as parabens and phthalates. Here, we identified the adverse effects of persistent exposure to such PCPs directly within human estrogen responsive breast tissue of subjects enrolled in a regimen of reduced XE use (REDUXE). Pre- and post-intervention fine needle aspirates (FNAs) of the breast were collected from healthy volunteers who discontinued the use of paraben and phthalate containing PCPs over a 28 d period. Based on high-dimensional gene expression data of matched FNA pairs of study subjects, we demonstrate a striking reversal of cancer-associated phenotypes, including the PI3K-AKT/mTOR pathway, autophagy, and apoptotic signaling networks within breast cells of REDUXE compliant subjects. These, and other altered phenotypes were detected together with a significant reduction in urinary parabens and phthalate metabolites. Moreover, in vitro treatment of paired FNAs with 17ß-estradiol (E2), displayed a 'normalizing' impact of REDUXE on gene expression within known E2-modulated pathways, and on functional endpoints, including estrogen receptor alpha: beta ratio, and S-phase fraction of the cell cycle. In a paradigm shifting approach facilitated by community-based participatory research, REDUXE reveals unfavorable consequences from exposure to XEs from daily-use PCPs. Our findings illustrate the potential for REDUXE to suppress pro-carcinogenic phenotypes at the cellular level towards the goal of breast cancer prevention.

Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus.

Microgravity (modeled by head-tilt bedrest and hind-limb unloading), experienced during prolonged spaceflight, results in neurological consequences, central nervous system (CNS) dysfunction, and potentially impairment during the performance of critical tasks. Similar pathologies are observed in bedrest, sedentary lifestyle, and muscle disuse on Earth. In our previous study, we saw that head-tilt bedrest together with social isolation upregulated the milieu of pro-inflammatory cytokines in the hippocampus and plasma. These changes were mitigated in a MCAT mouse model overexpressing human catalase in the mitochondria, pointing out the importance of ROS signaling in this stress response. Here, we used a head-tilt model in socially housed mice to tease out the effects of head-tilt bedrest without isolation. In order to find the underlying molecular mechanisms that provoked the cytokine response, we measured CD68, an indicator of microglial activation in the hippocampus, as well as changes in normal in-cage behavior. We hypothesized that hindlimb unloading (HU) will elicit microglial hippocampal activations, which will be mitigated in the MCAT ROS-quenching mice model. Indeed, we saw an elevation of the activated microglia CD68 marker following HU in the hippocampus, and this pathology was mitigated in MCAT mice. Additionally, we identified cytokines in the hippocampus, which had significant positive correlations with CD68 and negative correlations with exploratory behaviors, indicating a link between neuroinflammation and behavioral consequences. Unveiling a correlation between molecular and behavioral changes could reveal a biomarker indicative of these responses and could also result in a potential target for the treatment and prevention of cognitive changes following long space missions and/or muscle disuse on Earth.

Characteristics and predictors for silent hypoxemia in a cohort of hospitalized COVID-19 patients.

BACKGROUND: An intriguing feature recently unveiled in some COVID-19 patients is the "silent hypoxemia" phenomenon, which refers to the discrepancy of subjective well-being sensation while suffering hypoxia, manifested as the absence of dyspnea. OBJECTIVE: To describe the clinical characteristics and predictors of silent hypoxemia in hospitalized COVID-19 patients. METHODS: We conducted a prospective cohort study including consecutive hospitalized adult (≥ 18 years) patients with confirmed COVID-19 presenting to the emergency department with oxygen saturation (SpO2) ≤ 80% on room air from March 15 to June 30, 2020. We analyzed the characteristics, disease severity, and in-hospital outcomes of patients presenting with dyspnea and those without dyspnea (silent hypoxemia). RESULTS: We studied 470 cases (64.4% men; median age 55 years, interquartile range 46-64). There were 447 (95.1%) patients with dyspnea and 23 (4.9%) with silent hypoxemia. The demographic and clinical characteristics, comorbidities, laboratory and imaging findings, disease severity, and outcomes were similar between groups. Higher breathing and heart rates correlated significantly with lower SpO2 in patients with dyspnea but not in those with silent hypoxemia. Independent predictors of silent hypoxemia were the presence of new-onset headache (OR 2.919, 95% CI 1.101-7.742; P = 0.031) and presenting to the emergency department within the first eight days after symptoms onset (OR 3.183, 95% CI 1.024-9.89; P = 0.045). CONCLUSIONS: Patients with silent hypoxemia sought medical attention earlier and had new-onset headache more often. They were also likely to display lower hemodynamic compensatory responses to hypoxemia, which may underestimate the disease severity.

Overexpression of catalase in mitochondria mitigates changes in hippocampal cytokine expression following simulated microgravity and isolation.

Isolation on Earth can alter physiology and signaling of organs systems, including the central nervous system. Although not in complete solitude, astronauts operate in an isolated environment during spaceflight. In this study, we determined the effects of isolation and simulated microgravity solely or combined, on the inflammatory cytokine milieu of the hippocampus. Adult female wild-type mice underwent simulated microgravity by hindlimb unloading for 30 days in single or social (paired) housing. In hippocampus, simulated microgravity and isolation each regulate a discrete repertoire of cytokines associated with inflammation. Their combined effects are not additive. A model for mitochondrial reactive oxygen species (ROS) quenching via targeted overexpression of the human catalase gene to the mitochondria (MCAT mice), are protected from isolation- and/or simulated microgravity-induced changes in cytokine expression. These findings suggest a key role for mitochondrial ROS signaling in neuroinflammatory responses to spaceflight and prolonged bedrest, isolation, and confinement on Earth.

Neurologic manifestations in hospitalized patients with COVID-19 in Mexico City.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a systemic entity that frequently implies neurologic features at presentation and complications during the disease course. We aimed to describe the characteristics and predictors for developing in-hospital neurologic manifestations in a large cohort of hospitalized patients with COVID-19 in Mexico City. METHODS: We analyzed records from consecutive adult patients hospitalized from March 15 to June 30, 2020, with moderate to severe COVID-19 confirmed by reverse transcription real-time polymerase chain reaction (rtRT-PCR) for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neurologic syndromes were actively searched by a standardized structured questionnaire and physical examination, confirmed by neuroimaging, neurophysiology of laboratory analyses, as applicable. RESULTS: We studied 1,072 cases (65% men, mean age 53.2±13 years), 71 patients had pre-existing neurologic diseases (diabetic neuropathy: 17, epilepsy: 15, history of ischemic stroke: eight, migraine: six, multiple sclerosis: one, Parkinson disease: one), and 163 (15.2%) developed a new neurologic complication. Headache (41.7%), myalgia (38.5%), dysgeusia (8%), and anosmia (7%) were the most common neurologic symptoms at hospital presentation. Delirium (13.1%), objective limb weakness (5.1%), and delayed recovery of mental status after sedation withdrawal (2.5%), were the most common new neurologic syndromes. Age, headache at presentation, preexisting neurologic disease, invasive mechanical ventilation, and neutrophil/lymphocyte ratio ≥9 were independent predictors of new in-hospital neurologic complications. CONCLUSIONS: Even after excluding initial clinical features and pre-existing comorbidities, new neurologic complications in hospitalized patients with COVID-19 are frequent and can be predicted from clinical information at hospital admission.

Skeletal tissue regulation by catalase overexpression in mitochondria.

Accumulation of oxidative damage from excess reactive oxygen species (ROS) may contribute to skeletal aging and mediate adverse responses to physiological challenges. Wild-type (WT) mice and transgenic mice (male, 16 wk of age) with human catalase targeted to the mitochondria (mCAT) were analyzed for skeletal responses to the remodeling stimuli of combined hind-limb unloading and exposure to ionizing radiation (137Cs, 2 Gy). Treatment for 2 wk caused lipid peroxidation in the bones WT but not mCAT mice, showing that transgene expression mitigated oxidative stress. Ex vivo osteoblast colony growth rate was 95% greater in mCAT than WT mice and correlated with catalase activity levels (P < 0.005, r = 0.67), although terminal osteoblast and osteoclast differentiation were unaffected. mCAT mice had lower cancellous bone volume and cortical size than WT mice. Ambulatory control mCAT animals also displayed reduced cancellous and cortical structural properties compared with control WT mice. In mCAT but not WT mice, treatment caused an unexpectedly rapid radial expansion (+8% cortical area, +22% moment of inertia), reminiscent of compensatory bone growth during advancing age. In contrast, treatment caused similar structural deficits in cancellous tissue of mCAT and WT mice. In sum, mitochondrial ROS signaling via H2O2 was important for the acquisition of adult bone structure and catalase overexpression failed to protect cancellous tissue from treatment. In contrast, catabolic stimuli caused radial expansion in mCAT not WT mice, suggesting that mitochondrial ROS in skeletal cells act to suppress tissue turnover in response to remodeling challenges.

Direito social à educação no Brasil pós-1988: Programa Mais Educação e a PNAS na gestão da pobreza / Social law to education in Brazil post-1988: More Education Program and PNAS in poverty management / Derecho social a la educación en Brasil post-1988: Programa Más Educación y la PNAS en la gestión de la pobreza

O artigo versa sobre a articulação entre o Programa Mais Educação (PME) e a Política Nacional de Assistência Social (PNAS) como via de garantia do direito social à Educação no Brasil pós-1988. Para isso, analisa a Constituição Federal de 1988, a Lei de Diretrizes e Bases da Educação Nacional de 1996, a PNAS e o Programa Mais Educação, situando como os discursos da estatística, justiça, economia e território, que foram, nos documentos e historicamente, sendo integrados na formulação das políticas e programas de garantia do direito à Educação pós-1988. Por meio dos resultados, infere que as estratégias do Estado para o acesso universal ao direito à Educação entre o PME e PNAS, amparado sob o discurso da esfera pública como via para alteração das desigualdades sociais, possibilitaram gerir uma parcela específica da população: sujeitos carentes, pobres, vulneráveis ou em risco.

The article deals with the articulation between the More Education Program (PME) and the National Social Assistance Policy (PNAS) as a way of guaranteeing social law to Education in Brazil after 1988. For this, it analyzes the jurisdiction of the Federal Constitution of 1988, the Law on Guidelines and Bases of National Education of 1996, the PNAS and the More Education Program, situating as the discourses of statistics, justice, economy and territory were, in the documents and historically, integrated into the formulation of policies and programs to guarantee the right to Education after 1988. By means of the results show that the State's strategies for universal access to the right to Education between PMEs and PNAS, supported by the discourse of the public sphere, as a way to change social inequalities, made it possible to manage a certain part of the population: poor, vulnerable or at risk.

El artículo versa sobre la articulación entre el Programa Más Educación (PME) y la Política Nacional de Asistencia Social (PNAS) como vía de garantía del derecho social a la Educación en Brasil post-1988. Para ello, analiza la Constitución Federal de 1988, de la Ley de Directrices y Bases de la Educación Nacional de 1996, de la PNAS y del Programa Más Educación, situando como los discursos de la estadística, justicia, economía y territorio fueron, en los documentos e históricamente, siendo integrados en la formulación de las políticas y programas de garantía del derecho a la Educación, después de 1988. Por medio de los resultados se desprende que las estrategias del Estado para el acceso universal al derecho a la Educación entre la PME y el PNAS, amparado bajo el discurso de la esfera pública como vía para alteración de las desigualdades sociales, posibilitaron gestionar una parte de la población: sujetos carentes, pobres, vulnerables o en riesgo.

Influence of Social Isolation During Prolonged Simulated Weightlessness by Hindlimb Unloading.

The hindlimb unloading (HU) model has been used extensively to simulate the cephalad fluid shift and musculoskeletal disuse observed in spaceflight with its application expanding to study immune, cardiovascular and central nervous system responses, among others. Most HU studies are performed with singly housed animals, although social isolation also can substantially impact behavior and physiology, and therefore may confound HU experimental results. Other HU variants that allow for paired housing have been developed although no systematic assessment has been made to understand the effects of social isolation on HU outcomes. Hence, we aimed to determine the contribution of social isolation to tissue responses to HU. To accomplish this, we developed a refinement to the traditional NASA Ames single housing HU system to accommodate social housing in pairs, retaining desirable features of the original design. We conducted a 30-day HU experiment with adult, female mice that were either singly or socially housed. HU animals in both single and social housing displayed expected musculoskeletal deficits versus housing matched, normally loaded (NL) controls. However, select immune and hypothalamic-pituitary-adrenal (HPA) axis responses were differentially impacted by the HU social environment relative to matched NL controls. HU led to a reduction in % CD4+ T cells in singly housed, but not in socially housed mice. Unexpectedly, HU increased adrenal gland mass in socially housed but not singly housed mice, while social isolation increased adrenal gland mass in NL controls. HU also led to elevated plasma corticosterone levels at day 30 in both singly and socially housed mice. Thus, musculoskeletal responses to simulated weightlessness are similar regardless of social environment with a few differences in adrenal and immune responses. Our findings show that combined stressors can mask, not only exacerbate, select responses to HU. These findings further expand the utility of the HU model for studying possible combined effects of spaceflight stressors.

Relato de experiência da aproximação do CREPOP-RS ao meio acadêmico: formação em psicologia e políticas públicas / Experience report on the approximation of CREPOP-RS to the academic environment: training in psychology and public policy / Relato de experiencia de la aproximación del CREPOP-RS al entorno académico: formación en psicología y políticas públicas / Rapport d'expérience de l'approximation du centre de réference technique en psychologie et politiques publiques de l'état brésilien rio grande do sul (CREPOP-RS) au milieu académique: formation en psychologie et politiques publiques

Este relato de experiência discute o desenvolvimento de um projeto-piloto de aproximação do Centro de Referência Técnica em Psicologia e Políticas Públicas (CREPOP), do Conselho Regional de Psicologia do Rio Grande do Sul (CRP/RS), ao meio acadêmico. A aproximação objetivou fomentar a discussão sobre a formação em psicologia e as políticas públicas junto a estudantes e professores de graduação de duas universidades do estado do Rio Grande do Sul. O projeto foi executado em duas etapas: encontro com os estudantes inseridos em estágios e discussão sobre a temática seguida da sistematização dos dados obtidos; debate dos dados sistematizados com os professores que compõem o corpo docente do curso de psicologia de cada instituição. A partir dos resultados foi possível organizar os relatos dos estudantes nas seguintes categorias: 1) Presença da temática na formação; 2) Espaços de prática profissional; 3) Formação crítica; 4) Interdisciplinaridade; 5) Qualificação do corpo docente; 6) Atuação política; 7) Protagonismo estudantil. Por fim, avaliamos o projeto-piloto como um espaço potente de reflexão sobre a interface entre a formação em psicologia e as políticas públicas.

This experience report discusses the development of a pilot project for the approximation of the Centro de Referência Técnica em Psicologia e Políticas Públicas/Center for Technical Reference in Psychology and Public Policy (CREPOP), from the Conselho Regional de Psicologia do Rio Grande do Sul/Regional Council of Psychology of Rio Grande do Sul (CRP / RS), to the academic environment. The aim of this study was to foster a discussion about training in psychology and public policies among undergraduate students and professors from two universities in the state of Rio Grande do Sul. The project was carried out in two stages: a meeting with internship students and a discussion about the thematic followed by the systematization of the obtained data; discussion of systematized data with the professors who make up the faculty of the psychology course of each institution. From the results it was possible to organize the students' reports in the following categories: 1) Presence of the theme in training; 2) Spaces of professional practice; 3) Critical training; 4) Interdisciplinarity; 5) Qualification of teaching staff; 6) Political action; 7) Student protagonism. Finally, we evaluated the pilot project as a powerful space for reflection on the interface between training in psychology and public policy.

Este relato de experiencia discute el desarrollo de un proyecto-piloto de aproximación del Centro de Referencia Técnica en Psicología y Políticas Públicas (CREPOP), del 'Conselho Regional de Psicologia do Rio Grande do Sul' (CRP/RS), al entorno académico. La aproximación tuvo el objetivo de estimular la discusión sobre la formación en psicología y las políticas públicas junto a Estudiantes y profesores del grado de dos universidades del Estado del Rio Grande do Sul. El proyecto fue ejecutado en dos etapas: encuentro con estudiantes en pasantías y discusión sobre la temática seguida de la sistematización de los datos obtenidos; debate de los datos sistematizados con los profesores que componen el cuerpo docente del curso de psicología de cada institución. Con los resultados fue posible organizar los relatos de los estudiantes en las siguientes categorías: 1) Presencia de la temática en la formación; 2) Espacios de práctica profesional; 3) Formación crítica; 4) Interdisciplinaridad; 5) Cualificación del cuerpo docente; 6) Actuación política; 7) Protagonismo estudiantil. Por fin, evaluamos el proyecto-piloto como un potente espacio de reflexión sobre la interface entre la formación en psicología y las políticas públicas.

Ce rapport d'expérience discute le développement d'un projet-pilote d'approximation entre le Centre de Référence Technique en Psychologie et Politiques Publiques, le Conseil régional de Psychologie de l'état brésilien Rio Grande do Sul, et le milieu académique. L'approximation a eu l'objectif d'encourager le débat sur la formation en psychologie et les politiques publiques chez les élèves et les enseignants du premier cycle de deux universités dans l'état Rio Grande do Sul. Le projet a été réalisé en deux étapes: rencontre avec les étudiants stagiaires et débat sur le thème, suivi par la systématisation des données obtenues; discussion des données organisées avec les enseignants qui composent la faculté du cours de psychologie de chaque institution. D'après les résultats, il a été possible d'organiser les rapports d'étudiants dans les catégories suivantes: 1) Présence thématique dans la formation; 2) Espaces de pratique professionnelle; 3) Formation critique; 4) Interdisciplinarité; 5) Qualification du corps enseignant; 6) Action politique; 7) Le rôle central de l'étudiant. Enfin, nous avons évalué le projet-pilote comme un espace puissant de réflexion sur l'interface entre la formation en psychologie et les politiques publiques.

The Development of a Communication Tool to Facilitate the Cancer Trial Recruitment Process and Increase Research Literacy among Underrepresented Populations.

Despite increasing need to boost the recruitment of underrepresented populations into cancer trials and biobanking research, few tools exist for facilitating dialogue between researchers and potential research participants during the recruitment process. In this paper, we describe the initial processes of a user-centered design cycle to develop a standardized research communication tool prototype for enhancing research literacy among individuals from underrepresented populations considering enrollment in cancer research and biobanking studies. We present qualitative feedback and recommendations on the prototype's design and content from potential end users: five clinical trial recruiters and ten potential research participants recruited from an academic medical center. Participants were given the prototype (a set of laminated cards) and were asked to provide feedback about the tool's content, design elements, and word choices during semi-structured, in-person interviews. Results suggest that the prototype was well received by recruiters and patients alike. They favored the simplicity, lay language, and layout of the cards. They also noted areas for improvement, leading to card refinements that included the following: addressing additional topic areas, clarifying research processes, increasing the number of diverse images, and using alternative word choices. Our process for refining user interfaces and iterating content in early phases of design may inform future efforts to develop tools for use in clinical research or biobanking studies to increase research literacy.

Efficacy of the virtual reality-based stress management program on stress-related variables in people with mood disorders: the feasibility study.

This study aimed to investigate the effect of a VR-based stress management program on people with mood disorders. A quasi-experimental study was conducted in a tertiary hospital in Singapore, and a convenience sample of 22 was recruited. The program comprised three daily 1-hour sessions incorporating psychoeducation and VR-based relaxation practice. Participants who completed the program had significantly lowered subjective stress (t=6.91, p<0.001), depression (t=5.62, p<0.001), and anxiety (t=5.54, p<0.001); and increased skin temperature (F=17.71, p<0.001), perceived relaxation (F=26.20, p<0.001) and knowledge (F=13.77, p<0.001). Participants' feedback on the program was positive. Findings from this study contribute to improving clinical practice and serve as preliminary data to conduct more rigorous research in the future.

A experiência de discentes de enfermagem na capacitação de educadores infantis em primeiros socorros / The experience of nursing students in training educators in children first aid

Objetivo: descrever a experiência de discentes do Curso de Enfermagem durante a capacitação sobre primeiros socorros com educadores dos Centros Municipais de Educação Infantil em Santa Terezinha de Itaipu.Método: trata-se de um relato de experiência. Resultados: realizaram-se quatro capacitações participando 41 educadores, por meio de aulas expositivas e práticas. O grupo de educadores foi formado por mulheres, comidade entre 40 e 49 anos e tempo de atuação na educação infantil de 11 a 18 anos. As principais situações de emergência vivenciadas para maioria foi à convulsão (27%). Conclusão: esta experiência foi de extrema importância, uma vez que se referiu às ações interdisciplinares entre acadêmicos, profissionais da saúde e educação. Deste modo, tornou-se algo ímpar para a vivência enquanto estudante de enfermagem, pois continuamente foi-se instigado a se desenvolver e atuar como profissional.

Objetive: describe the experience of students of the undergraduate program in the accomplishment of continuing education on first aid educators with the Municipal Child Education Centers of Santa Terezinha de Itaipu. Method: this is an experience report. Results: there were four 41 educators attending training throughlectures and practical. There was a predominance of females, aged between 40 and 49 (39%), 11-18 (49%)years of experience in early childhood education. Major emergency situations experienced most was the seizure (27%). Conclusion: this experience was of paramount importance, since it referred to disciplinaryactions including academics, health professionals and education. Thus, it has become something unique to the experience as a student nurse, because we were continually encouraged to develop and act as professionals.

Efficacy of psychoeducation and relaxation interventions on stress-related variables in people with mental disorders: a literature review.

This paper aimed to critically review and summarize empirical evidence concerning the efficacy of psychoeducation or relaxation-based stress management interventions on stress-related variables in people with mental disorders. Electronic databases were used during the literature search. Thirteen articles that fulfilled the preset eligible criteria were included in the review. Findings indicated that psychoeducation and relaxation-based interventions mitigated stress and depression; and enhanced relaxation intensity and knowledge on stress management. However, mixed results were obtained on anxiety. In addition, interventions using virtual reality technology revealed positive effects on depression, relaxation intensity and anxiety. Limitations and recommendations for future research are discussed.

Velhice e Identidade: Significações de Mulheres Idosas / Aging and Identity: Meanings of Elderly Women

Este estudo é de caráter qualitativo e propõe reflexões sobre a construção da identidade em mulheres idosas. Foram realizadas entrevistas semi-estruturadas com seis idosas, e os dados foram analisados por meio da Análise Compreensiva de Base Fenomenológica. Constatou-se que a mulher idosa pode estar ressignificando seu papel na sociedade, e, hoje, ruma para a construção de um espaço social onde haja igualdade de direitos e deveres.(AU)

This paper presents the results of a survey that focus on reflections on the construction of identity in elderly women. Interviews were conducted by semi-structured form with six elderly women and the data were analyzed based on the Comprehensive Review of Phenomenological Base. Not reduce the subject to biological, genetic, social allows us to develop these projects and achievements in this time of life where the experience can lead to a better well-being and quality of life.(AU)

Velhice e Identidade: Significações de Mulheres Idosas / Aging and Identity: Meanings of Elderly Women

Este estudo é de caráter qualitativo e propõe reflexões sobre a construção da identidade em mulheres idosas. Foram realizadas entrevistas semi-estruturadas com seis idosas, e os dados foram analisados por meio da Análise Compreensiva de Base Fenomenológica. Constatou-se que a mulher idosa pode estar ressignificando seu papel na sociedade, e, hoje, ruma para a construção de um espaço social onde haja igualdade de direitos e deveres...

This paper presents the results of a survey that focus on reflections on the construction of identity in elderly women. Interviews were conducted by semi-structured form with six elderly women and the data were analyzed based on the Comprehensive Review of Phenomenological Base. Not reduce the subject to biological, genetic, social allows us to develop these projects and achievements in this time of life where the experience can lead to a better well-being and quality of life...

Differential effects of chronic hypoxia and intermittent hypocapnic and eucapnic hypoxia on pulmonary vasoreactivity.

Intermittent hypoxia (IH) resulting from sleep apnea can lead to pulmonary hypertension (PH) and right heart failure, similar to chronic sustained hypoxia (CH). Supplemental CO(2), however, attenuates hypoxic PH. We therefore hypothesized that, similar to CH, IH elicits PH and associated increases in arterial endothelial nitric oxide synthase (eNOS) expression, ionomycin-dependent vasodilation, and receptor-mediated pulmonary vasoconstriction. We further hypothesized that supplemental CO(2) inhibits these responses to IH. To test these hypotheses, we measured eNOS expression by Western blot in intrapulmonary arteries from CH (2 wk, 0.5 atm), hypocapnic IH (H-IH) (3 min cycles of 5% O(2)/air flush, 7 h/day, 2 wk), and eucapnic IH (E-IH) (3 min cycles of 5% O(2), 5% CO(2)/air flush, 7 h/day, 2 wk) rats and their respective controls. Furthermore, vasodilatory responses to the calcium ionophore ionomycin and vasoconstrictor responses to the thromboxane mimetic U-46619 were measured in isolated saline-perfused lungs from each group. Hematocrit, arterial wall thickness, and right ventricle-to-total ventricle weight ratios were additionally assessed as indexes of polycythemia, arterial remodeling, and PH, respectively. Consistent with our hypotheses, E-IH resulted in attenuated polycythemia, arterial remodeling, RV hypertrophy, and eNOS upregulation compared with H-IH. However, in contrast to CH, neither H-IH nor E-IH increased ionomycin-dependent vasodilation. Furthermore, H-IH and E-IH similarly augmented U-46619-induced pulmonary vasoconstriction but to a lesser degree than CH. We conclude that maintenance of eucapnia decreases IH-induced PH and upregulation of arterial eNOS. In contrast, increases in pulmonary vasoconstrictor reactivity following H-IH are unaltered by exposure to supplemental CO(2).