The bibliometric landscape of infectious disease research in Panama (1990-2019).

Background: This work aims to analyze the landscape of scientific publications on subjects related to One Health and infectious diseases in Panama. The research questions are: How does the One Health research landscape look like in Panama? Are historical research efforts aligned with the One Health concept? What infectious diseases have received more attention from the local scientific community since 1990? Methods: Boolean searches on the Web of Science, SCOPUS and PubMed were undertaken to evaluate the main trends of publications related to One Health and infectious disease research in the country of Panama, between 1990 and 2019. Results: 4546 publications were identified since 1990, including 3564 peer-reviewed articles interconnected with One Health related descriptors, and 211 articles focused particularly on infectious diseases. A pattern of exponential growth in the number of publications with various contributions from Panamanian institutions was observed. The rate of multidisciplinary research was moderate, whereas those of interinstitutional and intersectoral research ranged from low to very low. Research efforts have centered largely on protozoan, neglected and arthropod-borne diseases with a strong emphasis on malaria, Chagas and leishmaniasis. Conclusion: Panama has scientific capabilities on One Health to tackle future infectious disease threats, but the official collaboration schemes and strategic investment to develop further competencies need to be conciliated with modern times, aka the pandemics era. The main proposition here, addressed to the government of Panama, is to launch a One Health regional center to promote multidisciplinary, interinstitutional and intersectoral research activities in Panama and beyond.

Honokiol and Alpha-Mangostin Inhibit Mayaro Virus Replication through Different Mechanisms.

Mayaro virus (MAYV) is an emerging arbovirus with an increasing circulation across the Americas. In the present study, we evaluated the potential antiviral activity of the following natural compounds against MAYV and other arboviruses: Sanguinarine, (R)-Shikonin, Fisetin, Honokiol, Tanshinone IIA, and α-Mangostin. Sanguinarine and Shikonin showed significant cytotoxicity, whereas Fisetin, Honokiol, Tanshinone IIA, and α-Mangostin were well tolerated in all the cell lines tested. Honokiol and α-Mangostin treatment protected Vero-E6 cells against MAYV-induced damage and resulted in a dose-dependent reduction in viral progeny yields for each of the MAYV strains and human cell lines assessed. These compounds also reduced MAYV viral RNA replication in HeLa cells. In addition, Honokiol and α-Mangostin disrupted MAYV infection at different stages of the virus life cycle. Moreover, Honokiol and α-Mangostin decreased Una, Chikungunya, and Zika viral titers and downmodulated the expression of E1 and nsP1 viral proteins from MAYV, Una, and Chikungunya. Finally, in Honokiol- and α-Mangostin-treated HeLa cells, we observed an upregulation in the expression of type I interferon and specific interferon-stimulated genes, including IFNα, IFNß, MxA, ISG15, OAS2, MDA-5, TNFα, and IL-1ß, which may promote an antiviral cellular state. Our results indicate that Honokiol and α-Mangostin present potential broad-spectrum activity against different arboviruses through different mechanisms.

Targeting Host PIM Protein Kinases Reduces Mayaro Virus Replication.

Mayaro virus (MAYV) manipulates cell machinery to successfully replicate. Thus, identifying host proteins implicated in MAYV replication represents an opportunity to discover potential antiviral targets. PIM kinases are enzymes that regulate essential cell functions and also appear to be critical factors in the replication of certain viruses. In this study we explored the consequences of PIM kinase inhibition in the replication of MAYV and other arboviruses. Cytopathic effects or viral titers in samples from MAYV-, Chikungunya-, Una- or Zika-infected cells treated with PIM kinase inhibitors were evaluated using an inverted microscope or plaque-forming assays. The expression of viral proteins E1 and nsP1 in MAYV-infected cells was assessed using an immunofluorescence confocal microscope or Western blot. Our results revealed that PIM kinase inhibition partially prevented MAYV-induced cell damage and also promoted a decrease in viral titers for MAYV, UNAV and ZIKV. The inhibitory effect of PIM kinase blocking was observed for each of the MAYV strains tested and also occurred as late as 8 h post infection (hpi). Finally, PIM kinase inhibition suppressed the expression of MAYV E1 and nsP1 proteins. Taken together, these findings suggest that PIM kinases could represent an antiviral target for MAYV and other arboviruses.

Inhibition of p38 Mitogen-Activated Protein Kinase Impairs Mayaro Virus Replication in Human Dermal Fibroblasts and HeLa Cells.

Mayaro virus (MAYV) hijacks the host's cell machinery to effectively replicate. The mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK1/2 have emerged as crucial cellular factors implicated in different stages of the viral cycle. However, whether MAYV uses these MAPKs to competently replicate has not yet been determined. The aim of this study was to evaluate the impact of MAPK inhibition on MAYV replication using primary human dermal fibroblasts (HDFs) and HeLa cells. Viral yields in supernatants from MAYV-infected cells treated or untreated with inhibitors SB203580, SP600125, U0126, or Losmapimod were quantified using plaque assay. Additionally, viral protein expression was analyzed using immunoblot and immunofluorescence. Knockdown of p38⍺/p38ß isoforms was performed in HDFs using the PROTACs molecule NR-7h. Our data demonstrated that HDFs are highly susceptible to MAYV infection. SB203580, a p38 inhibitor, reduced MAYV replication in a dose-dependent manner in both HDFs and HeLa cells. Additionally, SB203580 significantly decreased viral E1 protein expression. Similarly, knockdown or inhibition of p38⍺/p38ß isoforms with NR-7h or Losmapimod, respectively, affected MAYV replication in a dose-dependent manner. Collectively, these findings suggest that p38 could play an important role in MAYV replication and could serve as a therapeutic target to control MAYV infection.

A Functional Ubiquitin-Proteasome System is Required for Efficient Replication of New World Mayaro and Una Alphaviruses.

Mayaro (MAYV) and Una (UNAV) are emerging arboviruses belonging to the Alphavirus genus of the Togaviridae family. These viruses can produce febrile disease with symptoms such as fever, headache, myalgia, skin rash and incapacitating poly-arthralgia. Serological studies indicate that both viruses are circulating in different countries in Latin America. Viruses need the host cell machinery and resources to replicate effectively. One strategy to find new antivirals consists of identifying key cellular pathways or factors that are essential for virus replication. In this study, we analyzed the role of the ubiquitin-proteasome system (UPS) in MAYV and UNAV replication. Vero-E6 or HeLa cells were treated with the proteasome inhibitors MG132 or Lactacystin, and viral progeny production was quantified using a plaque assay method. In addition, the synthesis of viral proteins was analyzed by Western blot and confocal microscopy. Our results indicate that treatment with proteasome inhibitors decreases MAYV and UNAV protein synthesis, and also causes a significant dose-dependent decrease in MAYV and UNAV replication. Proteasome activity seems to be important at the early stages of MAYV replication. These findings suggest that the ubiquitin-proteasome system is a possible pharmacological target to inhibit these neglected alphaviruses.

Parálisis diafragmática bilateral idiopática tratada con ventilación mecánica no invasiva / Idiopathic bilateral diaphragmatic paralysis with noninvasive mechanical ventilation

Resumen La parálisis diafragmática bilateral es infrecuente y puede ser idiopática o más comúnmente asociada a varias entidades. Describimos el caso de un varón de 61 años con antecedentes de asma bronquial quien desarrolló parálisis difragmática bilateral sin causa evidente, la cual es excepcional. El paciente presentó disnea progresiva y ortopnea, que no mejoraban con antibioterapia ni esteroides sistémicos, por lo que se descartaron diversas etiologías como neuralgia lateral amiotrófica y finalmente se le diagnosticó parálisis diafragmática lateral en base a la exploración física y las pruebas de imagen. Se inició ventilación mecánica no invasiva con gran mejoría clínica.

Bilateral paralysis of the diaphragm is uncommon and can be either idiopathic or more frequently associated with several medical conditions. We describe the case of a 61-year-old man with a history of asthma who developed severe bilateral diaphragmatic paralysis without any obvius cause, which is exceptional. The patient manifested progressive dyspnea and debilitating orthopnea with no improvement with antibiotics or systemic steroids. Different etiologies were discarded as amyotrophic lateral neuralgia, and he was diagnosed of bilateral diaphragmatic paralysis based on physical examination and imaging tests. Noninvasive mechanical ventilation was started with great clinical improvement.

Lista anotada de los bivalvos marinos del Perú / Checklist of the marine bivalves from Peru

Se presenta una lista taxonómica actualizada de 401 especies de bivalvos marinos del Perú, distribuidas en 62 familias y 195 géneros. Se considera la nomenclatura y clasificación en el contexto de los cambios recientes, incluyendo los trabajos de Bernard (1983) y Coan & Valentich-Scott (2012). Cada especie de la lista es comentada, teniendo en cuenta la distribución geográfica y el hábitat.

A checklist of the marine bivalve species from Peru is presented, this list has 401 species which are distributed in 65 families and 195 genera. The taxonomical classification and nomenclature is based on classical and current bibliography including Bernard (1983) and Coan & Valentich-Scott (2012). We give distribution and hábitat information about every species.

Impaired pressure natriuresis resulting in salt-sensitive hypertension is caused by tubulointerstitial immune cell infiltration in the kidney.

Immune cell infiltration of the kidney is a constant feature in salt-sensitive hypertension (SSHTN). We evaluated the relationship between the renal inflammation and pressure natriuresis in the model of SSHTN that results from transient oral administration of N(ω)-nitro-L-arginine methyl ester (L-NAME). Pressure natriuresis was determined in Wistar rats that received 4 wk of a high-salt (4% NaCl) diet, starting 1 wk after stopping L-NAME, which was administered alone (SSHTN group, n = 17) or in association with mycophenolate mofetil (MMF; MMF group, n = 15). The administration of MMF in association with L-NAME is known to prevent the subsequent development of SSHTN. Control groups received a high (n = 12)- and normal (0.4%)-salt diet (n = 20). Rats with SSHTN had increased expression of inflammatory cytokines and oxidative stress. The severity of hypertension correlated directly (P < 0.0001) with the number of tubulointerstitial immune cells and angiotensin II-expressing cells. Pressure natriuresis was studied at renal arterial pressures (RAPs) of 90, 110, 130, and 150 mmHg. Glomerular filtration rate was similar and stable in all groups, and renal blood flow was decreased in the SSHTN group. Significantly decreased natriuresis (P < 0.05) was found in the SSHTN group at RAPs of 130 and 150 mmHg, and there was an inverse correlation (P < 0.01) between the urinary sodium excretion and the number of tubulointerstitial inflammatory cells (lymphocytes and macrophages) and cells expressing angiotensin II. We conclude that tubulointerstitial inflammation plays a key role in the impairment of pressure natriuresis that results in salt-dependent hypertension in this experimental model.

Curcumin reverses glomerular hemodynamic alterations and oxidant stress in 5/6 nephrectomized rats.

The administration of curcumin before and throughout the study attenuates oxidant stress and glomerular hemodynamic alterations induced by 5/6 nephrectomy (5/6NX). The purpose of this work was to study if curcumin is able to reverse established glomerular hemodynamic alterations (e.g. hyperfiltration and glomerular hypertension) and oxidant stress in rats with 5/6NX. Curcumin (120 mg/kg) was given to rats with established renal injury (30 days after surgery) and continued for 30 days (days 31-60 of the study). All rats were studied on day 60 after surgery. Curcumin was able (a) to reverse 5/6NX-induced glomerular hypertension and hyperfiltration, (b) to induce cell proliferation and nuclear translocation of Nrf2 and (c) to reverse 5/6NX-induced oxidant stress and decrease in antioxidant enzymes. These beneficial effects of curcumin were associated with the ability of this antioxidant to reverse renal structural alterations, proteinuria, hypertension, interstitial fibrosis, fibrotic glomeruli, tubular atrophy and mesangial expansion. It has been shown for the first time that curcumin is able to reverse established oxidants stress glomerular hypertension and hyperfiltration in rats with 5/6NX. These novel findings may play a key role in the attenuation of proteinuria and progression of renal damage in rats with 5/6NX. These data suggest that curcumin may be useful to reverse established hemodynamic alterations and renal injury in patients with chronic renal failure.

Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats.

Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX) is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1) control, (2) 5/6NX, (3) 5/6NX +CUR, and (4) CUR (n = 8-10). Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60 mg/kg/day) starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.

Evaluación intraoperatoria de los cambios de longitud y offset durante el reemplazo total cadera / Intra-operative evaluation of offset in hip replacement: device design

Introducción: la recuperación de la longitud del miembro inferior y del offset después del reemplazo total de cadera es fundamental para el buen resultado del procedimiento. Algunos métodos descritos para restablecer estos parámetros no son precisos y tienen ciertas limitaciones. El objetivo de este artículo es presentar un nuevo instrumento calibrador para uso intraoperatorio. Materiales y métodos: se diseñó y desarrolló un instrumento calibrador que permite realizar mediciones de longitud de la extremidad y offset durante la artroplastia de cadera. Para establecer la concordancia de este método con las mediciones radiológicas, se utilizó el instrumento en 39 procedimientos de reemplazo total de cadera Resultados: se encontró que el promedio de las diferencias en la medición de longitud fue de 0,05 mm y para las mediciones del offset el promedio fue 2,43 mm, con un nivel de concordancia alto (κ = 0,96 para longitud y κ = 0,54 para offset). Discusión: se observa que el calibrador es una herramienta intraoperatoria útil y precisa para la determinación de longitud y offset intraoperatorios en comparación con la radiografía posoperatoria.

Sildenafil treatment prevents glomerular hypertension and hyperfiltration in rats with renal ablation.

BACKGROUND: Sildenafil treatment ameliorates progressive renal injury resulting from extensive renal ablation; however, modifications induced by sildenafil in the glomerular hemodynamic pathophysiology of the remnant kidney have not been investigated. AIM: To determine the effects of sildenafil in the glomerular microcirculation and their relation to histological damage in the renal ablation model. METHODS: Micropuncture studies were performed 60 days after 5/6 nephrectomy in rats that received no treatment, sildenafil (5 mg/kg/day) and reserpine, hydralazine and hydrochlorothiazide to maintain the blood pressure within normal levels. Sham-operated rats untreated and treated with sildenafil served as controls. RESULTS: As expected, renal ablation induced systemic and glomerular hypertension, hyperfiltration, proteinuria, glomerulosclerosis and tubulointerstitial inflammatory damage in the remnant kidney. Sildenafil treatment prevented single-nephron hyperfiltration and hypertension, suppressed renal arteriolar remodeling, ameliorated systemic hypertension and proteinuria, increased urinary excretion of cGMP and NO(2)(-)/NO(3)(-), decreased oxidative stress and improved histological damage in the remnant kidney. Normalization blood pressure with reserpine, hydralazine and hydrochlorothiazide did not modify glomerular hemodynamics, proteinuria or histological changes induced by renal ablation. CONCLUSIONS: Beneficial effects of sildenafil in the remnant kidney are associated with a reduction in the arteriolar remodeling, renal inflammatory changes and prevention of changes in the glomerular microcirculation.

Contribution of renal purinergic receptors to renal vasoconstriction in angiotensin II-induced hypertensive rats.

To investigate the participation of purinergic P2 receptors in the regulation of renal function in ANG II-dependent hypertension, renal and glomerular hemodynamics were evaluated in chronic ANG II-infused (14 days) and Sham rats during acute blockade of P2 receptors with PPADS. In addition, P2X1 and P2Y1 protein and mRNA expression were compared in ANG II-infused and Sham rats. Chronic ANG II-infused rats exhibited increased afferent and efferent arteriolar resistances and reductions in glomerular blood flow, glomerular filtration rate (GFR), single-nephron GFR (SNGFR), and glomerular ultrafiltration coefficient. PPADS restored afferent and efferent resistances as well as glomerular blood flow and SNGFR, but did not ameliorate the elevated arterial blood pressure. In Sham rats, PPADS increased afferent and efferent arteriolar resistances and reduced GFR and SNGFR. Since purinergic blockade may influence nitric oxide (NO) release, we evaluated the role of NO in the response to PPADS. Acute blockade with N(ω)-nitro-l-arginine methyl ester (l-NAME) reversed the vasodilatory effects of PPADS and reduced urinary nitrate excretion (NO(2)(-)/NO(3)(-)) in ANG II-infused rats, indicating a NO-mediated vasodilation during PPADS treatment. In Sham rats, PPADS induced renal vasoconstriction which was not modified by l-NAME, suggesting blockade of a P2X receptor subtype linked to the NO pathway; the response was similar to that obtained with l-NAME alone. P2X1 receptor expression in the renal cortex was increased by chronic ANG II infusion, but there were no changes in P2Y1 receptor abundance. These findings indicate that there is an enhanced P2 receptor-mediated vasoconstriction of afferent and efferent arterioles in chronic ANG II-infused rats, which contributes to the increased renal vascular resistance observed in ANG II-dependent hypertension.

Octylguanidine ameliorates the damaging effect of mercury on renal functions.

Mercurials are known to induce morphological and functional modifications in kidney. The protective effect of octylguanidine on the injury induced by Hg(2+) on renal functions was studied. Octylguanidine administered at a dose of 10 mg/kg body weight prevented the damage induced by Hg(2+) administration at a dose of 3 mg/kg body weight. The findings indicate that octylguanidine spared mitochondria from Hg(2+)-poisoning by preserving their ability to retain matrix content, such as accumulated Ca(2+) and pyridine nucleotides. The hydrophobic amine also protected mitochondria from the Hg(2+)-induced loss of the transmembrane potential, and from the oxidative injury of mitochondrial DNA. In addition, octylguanidine maintained renal functions, such as normal values of creatinine clearance and blood urea nitrogen (BUN), and serum creatinine after Hg(2+) administration. It is proposed that octylguanidine protects kidney by inhibiting Hg(2+) uptake to kidney tissue, and in consequence its binding to mitochondrial membrane through a screening phenomenon, in addition to its known action as inhibitor of permeability transition.

Effect of treatment with losartan on salt sensitivity and SGLT2 expression in hypertensive diabetic rats.

Sodium-glucose cotransporters (SGLTs) in the kidney, may be involved in hypertension, diabetes and salt sensitivity. We evaluate the effect of losartan on blood pressure (BP) and SGLT2 expression in diabetic rats with high or normal salt diet. Losartan prevented an increase in BP and SGLT2 expression in diabetic rats.

Mixoma mamario: presentación de un caso / Breast mixoma: case presentation

Los mixomas mamarios puros son tumores mesenquimales benignos extremadamente raros, los casos reportados del mismo son en su totalidad esporádicos. Por otra parte la mayoría de los mixomas mamarios reportados forman parte del complejo de Carney. Desde 1915 hasta la actualidad y contando el presente caso sólo se reportan 8 casos. Histopatológicamente aparecen como lesiones bien circunscritas, hipocelulares con núcleos picnóticos pequeños dispersos en una matriz extracelular mixoide. Se presenta un caso atendido en nuestra unidad por considerarse una rareza dentro de la patología mamaria benigna.

The pure myxomas of te breast are extremely rare benign mesenchymal tumors, the cases reported of himself are in their totality sporadic. On the other hand most of the myxomas mammary reported comprise the complex of Carney. From 1915 to the present time and counting the present case 8 are reported. Histological they appear as circumscribed injuries affluent, hypocellular with dispersed small picnotics nuclei in myxoide extracellular matrix. A sporadic case taken care in our unit appears to consider a rarest within the benign mammary pathology.

Carcinoma invasor de la mama: estadificación molecular del ganglio centinela / Breast invasive carcinoma: the molecular stratification of sentinel node

Demostrar que existe un grupo de pacientes estadios patológicos N0 que presentan metástasis en el estudio del ganglio centinela no diagnosticados por métodos de rutina. El estudio del análisis molecular nos informa o no sobre el pronóstico, y podría considerarse como factor independiente. Se observó una relación agrupando los casos de mayor riesgo conocido, detectándose una población de bajo riesgo en la que se obviaría la quimioterapia. Observamos, que si agrupamos las pacientes con Ki-67 mayor de 5 por ciento, la mayoría de los casos en las que se observaron micro metástasis estaban en este grupo; aceptamos una relación entre los dos factores pronóstico. Algo similar sucede con pacientes grado II y III; la relación con la existencia de micrometástasis es evidente, pudiendo aceptarse que existe un grupo de carcinomas de mama de menor agresividad; se plantea que estas pacientes no reciban tratamiento adyuvante, y no planificar tratamientos quirúrgicos agresivos.

Demonstrated that exist a group of patients with pathological stage No who present metastases in the study of sentinel nodule no diagnostic for routine method. The study of molecular analysis inform or not about the prognosis and be considered a prognosis independent factor. We observed a relation between the mayor risk known cases and detected a low risk population in which obviated the chemotherapy. We observed that grouped patients with Ki-67 raised of 5 % the majority of the cases in which observed micro metastases were in these group; we accepted a relationship between this two prognosis factors. Some similar occur with patient’s grade II and grade III; the relation with the existence of micro metastases is evident, and we accepted that exist a group of breast carcinoma of less aggressive; for these reason we planted that these patient does not receive adjuvant treatment, and no planned surgical aggressive treatment.

Mastopatía diabética: presentación de caso / Diabetic masthopathy: case presentation

La mastopatía diabética es una entidad poco frecuente y de relativa nueva definición que puede simular una neoplasia maligna. Se presenta principalmente en pacientes diabéticas premenopáusicas insulino-dependientes con antecedentes de hiperglucemias prolongadas. Su etiopatogenia se asocia con el depósito estromal de colágeno y una infiltración linfocitaria de células B de causa autoinmune. La presentación clínica y radiológica no permiten concluir con un diagnóstico certero, siendo necesario la realización de biopsia con aguja gruesa y en la mayoría de los casos biopsia incisional. Presentamos el manejo de un caso en nuestra unidad.

Diabetic masthead is uncommon breast lesion and relative new definition that can be mistaken by a malignant neoplasia. It is mostly described in premenopausal patient’s diabetic and insulin dependent with history of persistent hyperglycemia. The ethiopatogenic is associated with extensive lymphocytic infiltration mostly B cells is detected an autoimmune reaction. Neither clinical nor radiologic exams rule out malignancy, so core biopsy and even incision biopsy are mandatory: Ephiteloid fibroblast in dense fibrous stroma is unique to the condition in diabetics. We present a case report, diagnosed and treated in our center.

Renal interstitial adenosine is increased in angiotensin II-induced hypertensive rats.

Since marked renal vasoconstriction is observed in angiotensin II (ANG II)-mediated hypertensive rats, we studied the possible interaction between ANG II and adenosine in this model. ANG II was infused into male Wistar rats through osmotic minipumps (435 ng x kg(-1) x min(-1)) for 14 days. In sham and ANG II groups, renal tissue and interstitial adenosine were measured; both increased to a similar twofold extent in the ANG II-treated rats (31.40 +/- 4 vs. 62.0 +/- 8.4 nM, sham vs. ANG II, interstitial adenosine; P< 0.001). The latter decreased by 47% with the specific blockade of 5'-nucleotidase. Glomerular hemodynamics demonstrated marked renal vasoconstriction in the angiotensin-treated group, which was reverted by an adenosine A(1)-receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, 10 mug.kg(-1) x min(-1)). 5'-Nucleotidase and adenosine deaminase (ADA) activities were measured in the cytosolic and membrane fractions. Only the membrane ADA activity decreased from 1,202 +/- 80 to 900 +/- 50 mU/mg protein in the ANG II-treated rats (P< 0.05), as well as in their protein and mRNA expression. Despite the adenosine elevation, A(1) and A(2b) receptor protein did not change; in contrast, downregulation was observed in A(2a) receptor and upregulation in A(3) receptor. A similar pattern was found in the cortex and in the medulla; mRNA significantly decreased only in the A(3) receptor in both segments. These results suggest that the elevation of renal tissue and interstitial adenosine contributes to the renal vasoconstriction observed in the ANG II-induced hypertension and that it is mediated by a decrease in the activity and expression of ADA, increased production of adenosine, and an induced imbalance in adenosine receptors.