How to use polarity thinkingTM to manage tensions between accountability and learner agency when using a multipurpose portfolio?

Portfolios are often implemented to target multiple purposes, e.g. assessment, accountability and/or self-regulated learning. However, in educational practice, it appears to be difficult to combine different purposes in one portfolio, as interdependencies between the purposes can cause tensions. This paper explored directions to manage tensions that are inextricably linked to multipurpose portfolio use. We used a systems thinking methodology, that was based on the polarity thinkingTM framework. This framework provides a step-by-step approach to chart a polarity map® that can help to balance the tensions present in specific settings. We followed the steps of the framework to chart a polarity map for multipurpose portfolio use. Based on literature and our prior research, we selected one overarching polarity: accountability and learner agency. This polarity seems responsible for multiple tensions related to multipurpose portfolio use. We formulated values (potential benefits) and fears (tensions that can arise) of the two poles of this polarity. Then, we organised a session with stakeholders who work with the portfolio of the Dutch General Practice speciality programme. Together we formulated action steps and early warnings that can help to balance accountability and learner agency during multipurpose portfolio use. In addition to previous recommendations concerning portfolio use, we advocate that it is important to create a shared frame of reference between all involved with the multipurpose portfolio. During this process, the acknowledgement and discussion of tensions related to multipurpose portfolio use are vital.

How is self-regulated learning documented in e-portfolios of trainees? A content analysis.

BACKGROUND: It is assumed that portfolios contribute to self-regulated learning (SRL). Presence of these SRL processes within the documentation kept in portfolios is presupposed in common educational practices, such as the assessment of reflective entries. However, questions can be asked considering the presence of SRL within portfolios. The aim of this study was to gain insight into the documentation of SRL processes within the electronic (e)-portfolio content of medical trainees. SRL consists of numerous processes, for this study the focus was on self-assessment via reflection and feedback, goal-setting and planning, and monitoring, as these are the processes that health professions education research mentions to be supported by portfolios. METHODS: A database containing 1022 anonymous e-portfolios from General Practitioner trainees was used to provide descriptive statistics of the various available e-portfolio forms. This was followed by a quantitative content analysis of 90 e-portfolios, for which, a codebook was constructed to rate the documentation of the included SRL processes. RESULTS: The numbers of forms in the e-portfolios varied to a great extent. Content analysis showed a limited documentation of reflective entries, and available entries mainly described events and experiences without explanations and context. Feedback was generally limited to comments on what went well and lacked specificity, context and suggestions for future action. Learning goals and plans were short of specificity, but did contain challenging topics and different goals were compatible with each other. 75% of the e-portfolios showed (limited) signs of monitoring. CONCLUSIONS: The e-portfolio content showed limited documentation of SRL processes. As documentation of SRL requires time and asks for a high level of introspection and writing skills, one cannot expect documentation of SRL processes to appear in e-portfolio content without efforts.

Mentorship Needs for Radiation Oncology Residents: Implications for Programme Design.

AIMS: Mentorship during residency guides and supports professional and personal development. Despite this, mentorship programmes within many postgraduate medicine programmes, including radiation oncology, are not standard. The objective of this qualitative study was to carry out a needs assessment to determine the perceived mentorship needs and experiences of radiation oncology residents and faculty. MATERIALS AND METHODS: Radiation oncology residents and faculty from a single university were invited to participate in semi-structured interviews in September 2017. Interviews were audiotaped and transcribed verbatim. An inductive thematic analysis was carried out using NVivo Pro version 11. Data collection occurred until saturation. Codes were derived and a systematic framework was applied to yield emergent themes. Trustworthiness was verified through triangulation and member checking. RESULTS: Twenty interviews (10 residents and 10 faculty) took place between October and December 2017, at which point thematic saturation was achieved. Four major themes emerged: (i) the perceived experiences of residents and faculty with mentorship, (ii) the evolution of mentorship needs during residency training, (iii) the mechanisms of creating mentorship relationships and (iv) peer mentorship. CONCLUSIONS: In this study, the perceptions of mentorship from the perspective of radiation oncology residents and faculty were explored. Important areas of alignment and discordance were discovered. These insights will inform the development and implementation of a mentorship programme that can be adapted for use by other oncology training programmes.

Twelve Tips for programmatic assessment.

Programmatic assessment is an integral approach to the design of an assessment program with the intent to optimise its learning function, its decision-making function and its curriculum quality-assurance function. Individual methods of assessment, purposefully chosen for their alignment with the curriculum outcomes and their information value for the learner, the teacher and the organisation, are seen as individual data points. The information value of these individual data points is maximised by giving feedback to the learner. There is a decoupling of assessment moment and decision moment. Intermediate and high-stakes decisions are based on multiple data points after a meaningful aggregation of information and supported by rigorous organisational procedures to ensure their dependability. Self-regulation of learning, through analysis of the assessment information and the attainment of the ensuing learning goals, is scaffolded by a mentoring system. Programmatic assessment-for-learning can be applied to any part of the training continuum, provided that the underlying learning conception is constructivist. This paper provides concrete recommendations for implementation of programmatic assessment.

Abdominal aortic aneurysms with high thrombus signal intensity on magnetic resonance imaging are associated with high growth rate.

OBJECTIVES: A layer of intraluminal thrombus is commonly observed in abdominal aortic aneurysms (AAAs). The purpose of this study was to investigate whether AAAs with high thrombus signal intensity (SI) at T1-weighted (T1w) magnetic resonance imaging (MRI) exhibit a faster aneurysm growth rate. METHODS: This was a prospective follow-up study. Patients with a small AAA underwent MRI examinations at 6 month intervals. Aneurysm thrombus and psoas muscle SI at the point of maximal diameter on T1w images were measured and expressed as a ratio (thrombus SI/muscle SI). Based on these measurements, patients were categorized into three groups: AAA with relative thrombus SI above (group A) and below (group B) the mean relative thrombus SI of 1.20. Patients with AAA without thrombus constituted group C. Eight patients were scanned twice within 2 weeks to investigate scan-rescan reproducibility. Aneurysm growth rates were expressed as the change in maximal cross sectional area (cm(2)). RESULTS: A total of 35 patients (m/f: 26/9; age 72 ± 7 years; AAA maximal diameter 4.9 ± 0.5 cm) were included. Mean aneurysm growth rate for patients in group A (n = 11, 1.87 cm(2)/0.5 year) was two-fold higher than group B (n = 17, 0.78 cm(2)/0.5 year, p = .005) and eight-fold higher than group C (n = 7, 0.23 cm(2)/0.5 years, p = .004) at 6 months' follow-up. At 12 months' follow-up, the mean aneurysm growth rate remained significantly higher in group A (n = 7, 3.03 cm(2)/year) than groups B (n = 10, 1.63 cm(2)/year, p = .03) and C (n = 7, 0.73 cm(2)/year, p = .004). The reproducibility for thrombus SI measurements was found to be high with a coefficient of variation of 6.2%. Aneurysm maximal cross-sectional area at baseline was not significantly different for the three groups. CONCLUSIONS: Abdominal aortic aneurysms with high thrombus SI on T1w MR images are associated with higher aneurysm growth rates.

Leukocyte counts, myeloperoxidase, and pregnancy-associated plasma protein a as biomarkers for cardiovascular disease: towards a multi-biomarker approach.

We evaluated leukocyte counts and levels of CRP, fibrinogen, MPO, and PAPP-A in patients with stable and unstable angina pectoris, acute myocardial infarction, and healthy controls. All biomarkers were analyzed again after 6 months. Leukocyte counts and concentrations of fibrinogen, CRP, MPO, and PAPP-A were significantly increased in patients with acute myocardial infarction. Leukocyte counts and concentrations of MPO were significantly increased in patients with unstable angina pectoris compared with controls. After 6 months, leukocyte counts and MPO concentrations were still increased in patients with acute myocardial infarction when compared to controls. Discriminant analysis showed that leukocyte counts, MPO, and PAPP-A concentrations classified study group designation for acute coronary events correctly in 83% of the cases. In conclusion, combined assessment of leukocyte counts, MPO, and PAPP-A was able to correctly classify acute coronary events, suggesting that this could be a promising panel for a multibiomarker approach to assess cardiovascular risk.

Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital model.

BACKGROUND: Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce. OBJECTIVES: We describe the first murine model of acute thrombus formation upon plaque rupture to study atherothrombosis by intravital fluorescence microscopy. METHODS: Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe(-/-) mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy. RESULTS: Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L. CONCLUSIONS: Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo.

Angiotensin-converting enzyme 2 (ACE2) expression and activity in human carotid atherosclerotic lesions.

Angiotensin-converting enzyme (ACE)2 is a recently identified homologue of ACE. As ACE2 inactivates the pro-atherogenic angiotensin II, we hypothesize that ACE2 may play a protective role in atherogenesis. The spatiotemporal localization of ACE2 mRNA and protein in human vasculature and a possible association with atherogenesis were investigated using molecular histology (in situ hybridization, immunohistochemistry). Also, the ACE : ACE2 balance was investigated using enzymatic assays. ACE2 mRNA was expressed in early and advanced human carotid atherosclerotic lesions. In addition, ACE2 protein was present in human veins, non-diseased mammary arteries and atherosclerotic carotid arteries and expressed in endothelial cells, smooth muscle cells and macrophages. Quantitative analysis of immunoreactivity showed that total vessel wall expression of ACE and ACE2 was similar during all stages of atherosclerosis. The observed ACE2 protein was enzymatically active and activity was lower in the stable advanced atherosclerotic lesions, compared to early and ruptured atherosclerotic lesions. These results suggest a differential regulation of ACE2 activity during the progression of atherosclerosis and suggest that this novel molecule of the renin-angiotensin system may play a role in the pathogenesis of atherosclerosis.

Disruption of hedgehog signalling in ApoE - /- mice reduces plasma lipid levels, but increases atherosclerosis due to enhanced lipid uptake by macrophages.

Embryonic pathways are often re-expressed in adult pathology. Here we investigated the role of the morphogen hedgehog (hh), which we found to be re-expressed in atherosclerotic plaques. Male ApoE - /- mice were treated for 12 weeks with an anti-hh antibody (5E1) or a control IgG (1E6) starting at the age of 6 or 18 weeks. Inhibition of hh signalling induced a significant increase in total plaque area in the aortic arch, a result of an increase (54% and 36%, respectively) in the area of advanced plaques (atheromata). In mice treated with anti-hh, plaques contained large (18-35% > ctrl), lipid-filled, sometimes multinucleated macrophage foam cells. Plasma cholesterol levels decreased after anti-hh treatment. In bone marrow-derived macrophages, foam cell formation was enhanced after inhibition of hh signalling. Anti-hh treatment caused a 54-75% increase in early oxLDL uptake (10-240 min), which was scavenger receptor-mediated. After 3-24 h of oxLDL incubation, intense Oil red O staining as well as increased amounts of cholesterol esters were present in these macrophages after anti-hh treatment. Activation of the HH-signalling cascade by recombinant Shh induced a decrease in oxLDL uptake. Here we show that the hh-signalling pathway is one of the morphogenic pathways that regulate plasma lipid levels and atherosclerosis development and progression.

Animal models to study plaque vulnerability.

The need to identify and characterize vulnerable atherosclerotic lesions in humans has lead to the development of various animal models of plaque vulnerability. In this review, current concepts of the vulnerable plaque as it leads to an acute coronary event are described, such as plaque rupture, erosion, intraplaque hemorrhage and neovascularization. Recently developed animal models that have attempted to reproduce these concepts are described and evaluated based on their suitability in the study of vulnerable plaques. Although certain features of plaque vulnerability have been reported in animal models, a model encompassing all aspects of the vulnerable plaque is lacking.

Gene profiling of cathepsin K deficiency in atherogenesis: profibrotic but lipogenic.

Recently, we showed that cathepsin K deficiency reduces atherosclerotic plaque progression, induces plaque fibrosis, but aggravates macrophage foam cell formation in the ApoE -/- mouse. To obtain more insight into the molecular mechanisms by which cathepsin K disruption evokes the observed phenotypic changes, we used microarray analysis for gene expression profiling of aortic arches of CatK -/-/ApoE -/- and ApoE -/- mice on a mouse oligo microarray. Out of 20 280 reporters, 444 were significantly differentially expressed (p-value of < 0.05, fold change of > or = 1.4 or < or = - 1.4, and intensity value of > 2.5 times background in at least one channel). Ingenuity Pathway Analysis and GenMAPP revealed upregulation of genes involved in lipid uptake, trafficking, and intracellular storage, including caveolin - 1, - 2, - 3 and CD36, and profibrotic genes involved in transforming growth factor beta (TGFbeta) signalling, including TGFbeta2, latent TGFbeta binding protein-1 (LTBP1), and secreted protein, acidic and rich in cysteine (SPARC), in CatK -/-/ApoE -/- mice. Differential gene expression was confirmed at the mRNA and protein levels. In vitro modified low density lipoprotein (LDL) uptake assays, using bone marrow derived macrophages preincubated with caveolae and scavenger receptor inhibitors, confirmed the importance of caveolins and CD36 in increasing modified LDL uptake in the absence of cathepsin K. In conclusion, we suggest that cathepsin K deficiency alters plaque phenotype not only by decreasing proteolytic activity, but also by stimulating TGFbeta signalling. Besides this profibrotic effect, cathepsin K deficiency has a lipogenic effect owing to increased lipid uptake mediated by CD36 and caveolins.

Quantification of atherosclerotic plaque components using in vivo MRI and supervised classifiers.

In this work we aimed to study the possibility of using supervised classifiers to quantify the main components of carotid atherosclerotic plaque in vivo on the basis of multisequence MRI data. MRI data consisting of five MR weightings were obtained from 25 symptomatic subjects. Histological micrographs of endarterectomy specimens from the 25 carotids were used as a standard of reference for training and evaluation. The set of subjects was divided in a training set (12 subjects) and an evaluation set (13 subjects). Four different classifiers and two human MRI readers determined the percentages of calcified tissue, fibrous tissue, lipid core, and intraplaque hemorrhage on the subject level for all subjects in the evaluation set. Quantification of the relatively small amounts of calcium could not be done with statistical significance by either the classifiers or the MRI readers. For the other tissues a simple Bayesian classifier (Bayes) performed better than the other classifiers and the MRI readers. All classifiers performed better than the MRI readers in quantifying the sum of hemorrhage and lipid proportions. The MRI readers overestimated the hemorrhage proportions and tended to underestimate the lipid proportions. In conclusion, this pilot study demonstrates the benefits of algorithmic classifiers for quantifying plaque components.

Is there more than C-reactive protein and fibrinogen? The prognostic value of soluble CD40 ligand, interleukin-6 and oxidized low-density lipoprotein with respect to coronary and cerebral vascular disease.

Incidence of atherosclerosis and atherosclerosis-related complications will increase significantly in the coming decennia. Research identified many serum and plasma markers that are associated with cardiovascular disease. However, little is known about the prognostic value of these markers to identify patients at risk for future cardiovascular events. Therefore, we aimed to investigate the prognostic value of three of these markers (soluble CD40 ligand (sCD40L), interleukin-6 (IL-6) and oxidized low-density lipoprotein (oxLDL)) with respect to coronary vascular disease and stroke. For this reason the Medline database was searched for the period January 1999-January 2005. To be selected in our study, concentration of the marker had to be determined at baseline, follow-up period had to be longer than 3 months and an estimate of relative risk had to be available. Based on these criteria, 4 studies for sCD40L, 10 for IL-6 and 2 for oxLDL were selected. Relative risk estimates adjusted for potential confounders varied between 1.9 and 2.8 for sCD40L, between 1.1 and 3.1 for IL-6 and between 1.9 and 3.2 for oxLDL. In conclusion, this systematic review shows that sCD40L, IL-6 and oxLDL are associated with an increased relative risk of developing cardiovascular disease.

Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation.

BACKGROUND: Cathepsin K (catK), a lysosomal cysteine protease, was identified in a gene-profiling experiment that compared human early plaques, advanced stable plaques, and advanced atherosclerotic plaques containing a thrombus, where it was highly upregulated in advanced stable plaques. METHODS AND RESULTS: To assess the function of catK in atherosclerosis, catK(-/-)/apolipoprotein (apo) E(-/-) mice were generated. At 26 weeks of age, plaque area in the catK(-/-)/apoE(-/-) mice was reduced (41.8%) owing to a decrease in the number of advanced lesions as well as a decrease in individual advanced plaque area. This suggests an important role for catK in atherosclerosis progression. Advanced plaques of catK(-/-)/apoE(-/-) mice showed an increase in collagen content. Medial elastin fibers were less prone to rupture than those of apoE(-/-) mice. Although the relative macrophage content did not differ, individual macrophage size increased. In vitro studies of bone marrow derived-macrophages confirmed this observation. Scavenger receptor-mediated uptake (particularly by CD36) of modified LDL increased in the absence of catK, resulting in an increased macrophage size because of increased cellular storage of cholesterol esters, thereby enlarging the lysosomes. CONCLUSIONS: A deficiency of catK reduces plaque progression and induces plaque fibrosis but aggravates macrophage foam cell formation in atherosclerosis.

Compensatory enlargement and stenosis develop in apoE(-/-) and apoE*3-Leiden transgenic mice.

Atherosclerotic mouse models develop little ischemic organ damage and no infarctions, despite the presence of large atherosclerotic lesions. Therefore, we hypothesize that luminal changes do not follow atherosclerotic lesion development. Because a phenomenon that may explain the discrepancy between luminal changes and lesion size is vascular remodeling, we measured parameters of vascular remodeling in the carotid arteries (CAs), thoracic aorta (TA), and abdominal aorta (AA) of apolipoprotein E (apoE)-deficient (apoE(-/-)) and apoE*3-Leiden mice, 2 well-known mouse models of atherosclerosis. Atherosclerotic lesions were classified (American Heart Association [AHA] types II through V), and plaque thickness, compensatory enlargement versus constrictive remodeling, lumen diameter, stenosis, and media thickness were measured relative to the nondiseased arterial wall. In CAs, plaque thickness increased during atherogenesis. CAs showed compensatory enlargement (apoE(-/-) 55%, apoE*3-Leiden 38%). Regression analysis revealed a positive correlation between plaque and lumen area (for apoE(-/-), R=0.95; for apoE*3-Leiden, R=0.90). Medial thinning and elastolysis were also observed. During atherogenesis, lumen diameter decreased (apoE(-/-) -69%, apoE*3-Leiden -40%), and stenosis >70% developed. TA and AA showed similar features, but neither developed a progressive decrease in lumen diameter or stenosis >70%. In CAs, TA, and AA of apoE(-/-) and apoE*3-Leiden mice, atherogenesis is associated with compensatory enlargement, medial thinning, and elastolysis. A progressive decrease in lumen diameter and stenoses >70% occur only in CAs. Vascular remodeling is more prominent in apoE(-/-) mice.

Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype.

In the present study, we investigated the role of the CD40L-CD40 pathway in a model of progressive atherosclerosis. ApoE-/- mice were treated with an anti-CD40L antibody or a control antibody for 12 wk. Antibody treatment started early (age 5 wk) or was delayed until after the establishment of atherosclerosis (age 17 wk). In both the early and delayed treatment groups, anti-CD40L antibody did not decrease plaque area or inhibit lesion initiation or age-related increase in lesion area. The morphology of initial lesions was not affected, except for a decrease in T-lymphocyte content. Effects of anti-CD40L antibody treatment on the morphology of advanced lesions were pronounced. In both the early and delayed treatment groups, T-lymphocyte content was significantly decreased. Furthermore, a pronounced increase in collagen content, vascular smooth muscle cell/myofibroblast content, and fibrous cap thickness was observed. In the delayed treatment group, a decrease in lipid core and macrophage content occurred. Interestingly, advanced lesions of anti-CD40L antibody-treated mice exhibited an increased transforming growth factor beta1 immunoreactivity, especially in macrophages. In conclusion, both early and delayed treatment with an anti-CD40L antibody do not affect atherosclerotic lesion initiation but do result in the development of a lipid-poor collagen-rich stable plaque phenotype. Furthermore, delayed treatment with anti-CD40L antibody can transform the lesion profile from a lipid-rich to a lipid-poor collagen-rich phenotype. Postulated mechanisms of this effect on plaque phenotype are the down-regulation of proinflammatory pathways and up-regulation of collagen-promoting factors like transforming growth factor beta.

Angiotensin II induces transactivation of two different populations of the platelet-derived growth factor beta receptor. Key role for the p66 adaptor protein Shc.

Several signal transduction events induced by angiotensin II (AngII) binding to the angiotensin II type 1 receptor resemble those evoked by platelet-derived growth factor (PDGF) binding to the PDGF-beta receptor (PDGFbeta-R). We report here, in agreement with previous data, that AngII and PDGF-B-chain homodimer (PDGF-BB) stimulate tyrosine phosphorylation of the PDGFbeta-R. Both AngII and PDGF-BB stimulated the phosphorylation of PDGFbeta-R via the binding of tyrosine-phosphorylated Shc to PDGFbeta-R. Both PDGF-BB- and AngII-induced phosphorylation of the Shc.PDGFbeta-R complex was inhibited by antioxidants such as N-acetylcysteine and Tiron, but not by calcium chelation. However, transactivation of PDGFbeta-R by AngII (measured by PDGFbeta-R tyrosine phosphorylation) differed significantly from PDGF-BB. Evidence to support different mechanisms of PDGFbeta-R phosphorylation includes differences in the time course of PDGFbeta-R phosphorylation, differing effects of inhibitors of the endogenous PDGFbeta-R tyrosine kinase and Src family tyrosine kinases, differing results when the PDGFbeta-R was directly immunoprecipitated (PDGFbeta-R-antibody) versus coimmunoprecipitated (Shc-antibody), and cell fractionation studies that suggested that the Shc.PDGFbeta-R complexes phosphorylated by AngII and PDGF-BB were located in separate subcellular compartments. These studies are the first to suggest that transactivation of tyrosine kinase receptors by G protein-coupled receptors involves a unique pathway that regulates a population of tyrosine kinase receptors different from the endogenous tyrosine kinase ligand.

Effects of angiotensin II on cardiac function and peripheral vascular structure during compensated heart failure in the rat.

UNLABELLED: The present experiments were designed to test the hypothesis that the activation of the renin-angiotensin system during compensated heart failure may have adverse effects on cardiac function and change the peripheral vascular structure. ANG II (250 ng/kg/min) or saline (0.9% NaCl) were infused in myocardial-infarcted and sham-operated rats. After 2 weeks, cardiac function and peripheral vascular changes were investigated. RESULTS: ANG II infusion reduced baseline cardiac index in sham rats but did not further reduce this index in ANG II-infused MI rats. Total peripheral resistance was similarly increased in ANG II-infused infarcted and sham rats, and also plasma ANG II concentrations were comparable. ANG II elevated systolic blood pressure by approximately 70 mm Hg in sham rats and increased the medial cross-sectional area of the superior mesenteric artery by 33%. However, ANG II infusions in MI rats resulted in only a minor increase in blood pressure, whereas the cross-sectional area of the superior mesenteric artery did not change. ANG II infusion had no effect on vessel dimensions of the resistance arteries of the pulmonary and mesenteric vascular bed of either group. Calculated ED50 and peak pressor response to acute ANG II injections were comparable in all groups, confirming the presence of functionally intact AT1 receptors. The increases in plasma atrial natriuretic peptide (ANP) and nitric oxide (NO) synthase activity (estimated by aortic cyclic GMP concentrations) were higher in ANG II-infused MI rats than in ANG II-infused sham rats. CONCLUSION: ANG II infusion in rats with and without MI has comparable negative effects on cardiac function but has different effects on blood pressure and vascular structure. The concomitant increases in plasma ANP and NO synthase activity in ANG II-infused MI rats suggest that the growth stimulatory and hypertensive actions of ANG II in sham rats may be counter-regulated by activation of inhibitory neurohumoral systems such as ANP or NO in MI rats.