Using Quality Improvement as a Mechanism for Fostering Partnerships and Promoting Equity in a Health System Change Model.

PURPOSE: Quality improvement (QI) processes provide a framework for systematically examining target outcomes and what changes can be made to result in improvement and ensure equity. We present a case study of how QI processes were used as a means of partnership building to enhance equity in designing materials for a Medicaid pilot program, North Carolina Integrated Care for Kids (NC InCK). DESCRIPTION: The NC InCK model addresses social determinants of health by providing structured care integration across core child health and social service areas and using an alternative payment model to incentivize high quality child outcomes. During the two-year planning period prior to the NC InCK model launch, we used Plan-Do-Study-Act (PDSA) cycles to conduct usability testing as a QI strategy for a component of the NC InCK model: the Shared Action Plan (SAP). ASSESSMENT: We conducted usability testing with four Family Council members, nine care managers, and one physician. Participants reviewed the SAP and provided feedback via a survey. After reviewing feedback with InCK leadership and the Family Council, we implemented recommendations that led to a SAP that uses clear and accessible language, that highlights family strengths and family-identified goals, and that is distinct from other care management plans. CONCLUSION: Usability testing forced refinement of materials before NC InCK launched, created opportunities for building and enhancing community partnerships and promoted equity within the NC InCK team and Family Council by considering multiple perspectives when deciding on SAP revisions.

Developing State Leadership in Maternal and Child Health: Process Evaluation Findings from a Work-Based Learning Model for Leadership Development.

OBJECTIVES: Since 2013 the MCH Bureau has supported the National MCH Workforce Development Center to strengthen the Title V MCH workforce. This article describes the Center's Cohort Program and lessons learned about work-based learning, instruction, and coaching. DESCRIPTION: The Cohort Program is a leadership development program that enrolls state-level teams for skill development and work-based learning to address a self-identified challenge in their state. Teams attend a Learning Institute that teaches concepts, skills, and practical tools in systems integration; change management and adaptive leadership; and evidence-based decision-making and implementation. Teams then work back home on their challenges, aided by coaching. The Program's goals are for teams to expand and use their skills to address their challenge, and that teams would strengthen programs, organizations, and policies, use their skills to address other challenges, and ultimately improve MCH outcomes. METHODS: This process evaluation is based on evaluation forms completed by attendees at the three-day Learning Institute; six-month follow-up interviews with team leaders; and a modified focus group with staff. RESULTS: Participants and staff believe the Cohort Program effectively merges a practical skill-based curriculum, work-based learning in teams, and coaching. The Learning Institute provides a foundation of skills and tools, strengthens the team's relationship with their coach, and builds the team. The work-based learning period provides structure, accountability, and a "practice space" for teams to apply the Cohort Program's skills and tools to address their challenge. In this period, teams deepen collaborations and often add partners. The coach provides accessible and tailored guidance in teamwork and skill application. These dimensions helped teams in develop skills and address state-level MCH challenges. CONCLUSIONS FOR PRACTICE: Continuing professional development programs can help leaders learn to address complex state-level MCH challenges through integrated classroom-based skills development, work-based learning on state challenges, and tailored coaching.

Enhancing Title V Workforce Capacity to Address Complex Challenges: Impact of the National Maternal and Child Health Workforce Development Center.

INTRODUCTION: The National Maternal and Child Health Workforce Development Center provides training, coaching, and consultation to Title V programs. The flagship experience is the Cohort program, a 6-8-month leadership development program where Title V programs convene a multisector team to address a pre-selected state/jurisdictional challenge related to health systems transformation. The overall objective of this paper is to demonstrate the impact of skills developed via the Cohort program on state/jurisdictional capacities to address complex challenges. METHODS: Qualitative, post-Cohort evaluation data were analyzed using inductive and deductive coding and the "Sort and Sift, Think and Shift" method. Themes and supporting text were summarized using episode profiles for each team and subsequently organized using the EvaluLEAD methodology for identifying and documenting impact. RESULTS: Teams brought an array of challenges related to health systems transformation and 94% of teams reported achieving progress on their challenge six-months after the Cohort program. Teams described how the Cohort program improved workforce skills in strategic thinking, systems thinking, adaptive leadership, and communication. Teams also reported the Cohort program contributed to stronger partnerships, improved sustainability of their project, produced mindset shifts, and increased confidence. The Cohort program has also led to improved population health outcomes. DISCUSSION: Through working with the Center, Title V leaders and their teams achieved episodic, developmental, and transformative results through application of Center tools and skills to complex challenges. Investment in the MCH workforce through skill development is critical for achieving transformative results and solving "wicked" public health problems.

Putting Implementation Science into Practice: Lessons from the Creation of the National Maternal and Child Health Workforce Development Center.

Purpose This article describes how implementation science informed the design of a national training and technical assistance (TA) center, and how implementation best practices have been used to improve the quality of training and technical assistance services offered to states/jurisdictions. Description An existing tool, based on the Implementation Drivers Framework (in: Fixsen et al., Implementation research: a synthesis of the literature, University of South Florida, The National Implementation Research Network, Tampa, 2005), was adapted to assess efforts of the National MCH Workforce Development Center (the Center) against known implementation best practices. Staff identified specific examples of effective practice and gaps for inclusion in this article. Assessment Using implementation science to establish, assess and improve Center practice was both feasible and practical, requiring intentionality, dedicated time, and staff committed to deepening their understanding of implementation science. The Implementation Drivers framework proved useful for creating a shared approach to analysis and identification of opportunities for improvement of Center practice. Conclusion Policymakers and funding agencies should consider how training and technical assistance programs demonstrate knowledge and use of implementation science best practices among other evidence based practices in their work. Increasing attention to the use of implementation science can contribute to a higher quality of service among technical assistance centers, with the long term goal of improving outcomes for training and assistance recipients and the communities they serve. Establishing the link between customer satisfaction and quality of technical assistance, on the one hand, and long term outcomes, on the other, remains a challenge and an area of focus and learning for the Center.

Clonal hematopoiesis related TET2 loss-of-function impedes IL1ß-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells.

Clonal hematopoiesis (CH) is defined as a single hematopoietic stem/progenitor cell (HSPC) gaining selective advantage over a broader range of HSPCs. When linked to somatic mutations in myeloid malignancy-associated genes, such as TET2-mediated clonal hematopoiesis of indeterminate potential or CHIP, it represents increased risk for hematological malignancies and cardiovascular disease. IL1ß is elevated in patients with CHIP, however, its effect is not well understood. Here we show that IL1ß promotes expansion of pro-inflammatory monocytes/macrophages, coinciding with a failure in the demethylation of lymphoid and erythroid lineage associated enhancers and transcription factor binding sites, in a mouse model of CHIP with hematopoietic-cell-specific deletion of Tet2. DNA-methylation is significantly lost in wild type HSPCs upon IL1ß administration, which is resisted by Tet2-deficient HSPCs, and thus IL1ß enhances the self-renewing ability of Tet2-deficient HSPCs by upregulating genes associated with self-renewal and by resisting demethylation of transcription factor binding sites related to terminal differentiation. Using aged mouse models and human progenitors, we demonstrate that targeting IL1 signaling could represent an early intervention strategy in preleukemic disorders. In summary, our results show that Tet2 is an important mediator of an IL1ß-promoted epigenetic program to maintain the fine balance between self-renewal and lineage differentiation during hematopoiesis.

What implementation strategies are relational? Using Relational Theory to explore the ERIC implementation strategies.

The identification and use of implementation strategies in implementation research and practice have strengthened our understanding of the implementation process as well as the causal pathways between mechanisms, strategies, and implementation outcomes. Although these contributions have advanced the application of strategies, there is still a need to learn more about how strategies might integrate relational exchanges and interactions. The inclusion of critical perspectives has been limited in implementation science, and theories such as Relational Theory can expand our understanding of the relational nature of implementation and enhance rigor through alternative theoretical applications. This study applied Relational Theory through a qualitative directed content analysis of the 73 Expert Recommendations for Implementation Change (ERIC) implementation strategies and examine relational components in strategy descriptions. Three reviewers used the structured approach to review and categorize the implementation strategies based on the Relational and Transactional Strategy Continuum measure, which operationalizes types of interactions, exchanges and alliances. Relational alliance strategies are those in which there is mutual growth and accountability, frequent interaction, shared power, and potential vulnerability. Operational alliances include forms of working exchanges between parties with balanced transactional and relational features. Operational alliances can be somewhat interactive in nature, with minor exchanges and limited accountability. Transactional alliance strategies are mostly uni-directional, influenced by power differentials, and do not require mutual growth, commitment, or exchange; thus, the power of growth is inherently one-sided. Results from the review suggest more implementation strategies with relational alliance features (highly relational, n = 17, semi-relational, n = 19) compared to transactional (highly transactional, n = 9, semi-transactional, n = 10) and 18 strategies coded as operational alliances. The qualitative review revealed opportunities to further expand how relational exchanges are considered within the implementation strategies descriptions, as well as the role of actors and power dynamics within strategy exchanges. The Relational and Transactional Strategy Continuum measure can help practitioners and researchers consider the sequencing, pairing, and impact on outcomes of different types and combinations of strategies in implementation practice and research. Additionally, the measure can support reflection on strategies that promote positive alliances, frequent connections, bi-directional communication, and power sharing.

The Use of Implementation Science Tools to Design, Implement, and Monitor a Community-Based mHealth Intervention for Child Health in the Amazon.

It is essential to analyze the local context and implementation components to effectively deliver evidence-based solutions to public health problems. Tools provided by the field of implementation science can guide practitioners through a comprehensive implementation process, making innovations more adaptable, efficient, and sustainable. It is equally important to report on the design and implementation process so others can analyze, replicate, and improve on the progress made from an intervention. The current study reports on the design and implementation of an mHealth intervention to improve child health in the Amazon of Peru. The study aims to provide insight into how an implementation science tool can be used to improve implementation and reporting of an evidence-based intervention in a global health setting. Methods: Implementation of a community-based mHealth intervention is analyzed and reported through the lens of the Active Implementation Frameworks (AIF). The AIF is used to analyze the design, implementation, adaptation, and monitoring of the intervention. The implementation process is categorized in the four stages of implementation. The results of the analysis and subsequent implementation activities are reported. Results: The exploration stage was used to learn about the local context in the Amazonian communities and identify an evidence-based solution to address poor child health. Several potential solutions were combined to create an innovative mHealth tool. During the installation stage, the stakeholders worked together to improve the intervention and plan for implementation through human-centered design. The providers in the field were trained and data was gathered to monitor implementation. During initial implementation stage, electronic tablets were distributed to community health agents and continuous quality improvement activities allowed for rapid improvements to be implemented. The intervention moved on to full implementation stage as acceptance and fidelity approached 100%. Conclusion: The AIF highlighted several potential barriers to implementation that may have been overlooked without the guidance of a science-based implementation tool. Reporting on the implementation process shows how implementation science tools can be used to foresee and address potential threats to successful implementation. The results of this study provide insight into the components of implementation in Amazonian communities, as well as the process of using implementation science tools in any global health setting.

Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are characterized by their ability to differentiate into all hematopoietic cell lineages while retaining their capacity for self renewal. One of the predictions of this model is the existence of a heterogeneous pool of HSCs, some members of which are destined to become lineage restricted progenitor cells while others function to renew the stem cell pool. To test whether HSCs are heterogeneous with respect to cell cycle status, we determined the fraction of phenotypically defined murine HSCs (Thy1.1lo Lin-/lo Sca-1+) that contain > 2n amount of DNA as measured by propidium iodide staining, Hoechst dye uptake and [3H]thymidine labeling; that fraction is 18-22%. In contrast, in the developing fetal liver, 40% of HSCs are in the S/G2/M phases of the cell cycle. Those HSCs which exhibit a low level of staining with rhodamine 123 are almost exclusively in G0/G1 (97%) whereas only 70% of HSCs which stain brightly for rhodamine 123 are in G0/G1. The injection of 100 G0/G1 HSCs rescued 90% of lethally irradiated mice in contrast to 100 S/G2/M HSCs, which protected only 25% of lethally irradiated recipients. Enhanced long-term donor-derived multilineage reconstitution of the peripheral blood was observed in recipients of 100 G0/G1 HSCs compared to recipients of 100 S/G2/M cells. These data indicate that a significant proportion of HSCs are actively proliferating during steady state hematopoiesis and that this subpopulation of cells exhibits reduced stem cell activity.

DDT contamination at Wheeler National Wildlife Refuge.

Disposal of industrial waste resulted in massive DDT contamination at Wheeler National Wildlife Refuge, Alabama. Nearly a decade after the cessation of DDT manufacturing at the facility responsible, concentrations of DDT residues in the local fauna are still high enough to suggest avian reproductive impairment and mortality. Populations of fish-eating birds are low, endangered species are being exposed, and muscle lipids of game birds contain up to 6900 parts of DDT (isomers and metabolites) per million.

Heterogeneity of hematopoietic stem cells.

Hematopoietic stem cells are capable of multi-lineage differentiation to all blood cell types as well as self-renewal and radioprotection. Thy-1.1lo Lin-/lo Sca-1+ cells are a heterogeneous mixture of quiescent and self-renewing hematopoietic stem cells as well as multi-lineage expanding cells.

Ectopic parathyroid adenoma with Tc-99m MIBI washout: role of SPECT.

The authors present a case of a 71-year-old woman with clinical and biochemical features of primary hyperparathyroidism and a history of right pneumonectomy. An ultrasound scan did not demonstrate any abnormality. A planar Tc-99m methoxyisobutylisonitrile (Tc-99m MIBI) scan showed an area of minimally increased uptake within the right hemithorax. However, unlike most adenomas, this demonstrated washout similar to the thyroid at 90 minutes and 3 hours. Subsequent SPECT imaging clearly showed the lesion in the superior right hemithorax. A CT scan and angiogram confirmed the presence of this mass. After surgery, histology confirmed the diagnosis of a parathyroid adenoma. Postoperatively, the calcium and PTH levels returned to normal.

Thymic origin of the prolactin-dependent Nb2 lymphoma cell line.

Blast cells in acute leukemia and lymphoma appear to be "frozen" at various stages of lymphoid cell differentiation. The enzymatic and antigenic phenotypes expressed by these cells often correspond to the gene products of their normal precursors. We have used various immunocytochemical and enzymatic techniques to identify membrane, nuclear, and cytoplasmic markers associated with the prolactin-dependent Nb2 lymphoma cell line. The Nb2 cells, whether stationary or in log-phase growth, did not express any surface immunoglobulin. However, 100% of the Nb2 cells bound both a monoclonal antibody raised to rat thymocyte W3/25-HLK, which specifically binds an antigenic determinant on rat T-helper cells, and second monoclonal antibody OX8-HL, which identifies rat nonhelper T-cells. Transmission electron microscopy showed no evidence of phagocytic vacuoles, and activity of the lysosomal enzyme muramidase was also absent. There was no evidence of the DNA polymerase enzyme terminal deoxynucleotidyl transferase. alpha-Naphthyl acetate esterase activity was indicated in about 50% of the Nb2 cells by a faint particulate cytoplasmic staining similar to that found in thymocytes. Rosette formation with guinea pig erythrocytes, a property of mature rat thymocytes, was not observed with Nb2 cells. The data suggest that the Nb2 tumor may have arisen from a thymocyte at an intermediate stage of differentiation. The presence of Thy-like alpha-naphthyl acetate esterase pattern and the binding of both W3/25-HLK and OX8-HL support the thymic origin and relative immaturity of these lymphoid cells. It is becoming increasingly apparent that a significant proportion of lymphomas and leukemias also originate in undifferentiated thymic cels.

Prevalence of multidrug resistance related to activation of the mdr1 gene in human sarcoma mutants derived by single-step doxorubicin selection.

Fluctuation analysis experiments were performed in the human sarcoma cell line MES-SA to assess whether selection or induction mechanisms determine resistance to doxorubicin (DOX), mutation rates, and the nature of the surviving clones. Thirteen flasks were seeded with 2000 cells/flask and grown to confluent populations of approximately 3.3 x 10(6) cells. After reseeding in 96-well plates, each population was treated with 40 nM DOX for 2 weeks. Surviving colonies were scored and harvested. Clones were propagated and analyzed for drug resistance phenotype. Expression of the mdr1, mrp, and topoisomerase II alpha and II beta genes was analyzed by reverse transcription-polymerase chain reaction. Accumulation of the P-glycoprotein substrate rhodamine-123 was measured by flow cytometry, with and without the cyclosporin D analogue SDZ PSC 833. Cellular glutathione levels were measured by flow cytometry, and M(r) 110,000 vesicular protein (p110) expression was detected by immunohistochemistry. Analysis of variance supported the hypothesis of spontaneous mutations rather than induction conferring DOX resistance. At this stringent level (5-6 log cell killing) of drug exposure, the mutation rate was estimated at 1.8 x 10(-6) per cell generation. All 30 propagated clones demonstrated cross-resistance to vinblastine, etoposide, and paclitaxel (Taxol), but not to cisplatin or bleomycin. Increased mRNA levels of mdr1 were observed in all 27 clones tested, including at least 1 from each of the 13 populations. No alterations were found in expression or level of topoisomerase II alpha or II beta, mrp, glutathione, and p110. Expression of P-glycoprotein was confirmed by flow cytometry using the monoclonal antibody UIC2. In almost all tested clones, decreased intracellular rhodamine-123 accumulation was modulated by 2 microM SDZ PSC 833, and the vinblastine resistance in all examined clones was completely reversed by SDZ PSC 833 and verapamil. Our study demonstrates that survival of cells exposed to DOX in a single step occurs as a result of a stochastic process consistent with mutational events. Activation of the mdr1 gene is the predominant mechanism selected by DOX in these resistant clones.

Expression of the c-myc protooncogene in human prostatic carcinoma and benign prostatic hyperplasia.

We have examined the level of c-myc transcripts in prostate tissue obtained from patients with both benign prostatic hyperplasia and adenocarcinoma of the prostate. A significantly higher level of c-myc transcripts is observed in patients with adenocarcinoma (P less than 0.05). In addition, a subset of patients with adenocarcinoma had levels of c-myc transcripts 2-fold higher than the mean level for this group. These preliminary results indicate that the investigation of c-myc levels as a prognostic indicator in prostatic carcinoma is warranted.

Transforming community prevention systems for sustained impact: embedding active implementation and scaling functions.

Traditional efforts to translate evidence-based prevention strategies to communities, at scale, have not often produced socially significant outcomes or the local capacity needed to sustain them. A key gap in many efforts is the transformation of community prevention systems to support and sustain local infrastructure for the active implementation, scaling, and continuous improvement of effective prevention strategies. In this paper, we discuss (1) the emergence of applied implementation science as an important type 3-5 translational extension of traditional type 2 translational prevention science, (2) active implementation and scaling functions to support the full and effective use of evidence-based prevention strategies in practice, (3) the organization and alignment of local infrastructure to embed active implementation and scaling functions within community prevention systems, and (4) policy and practice implications for greater social impact and sustainable use of effective prevention strategies.

Postnatal atresia of extraparenchymal pulmonary veins, fulminant necrotizing pulmonary arteritis and elevated circulating immune complexes.

An infant with operatively corrected total anomalous pulmonary venous connection developed postnatal atresia of the extraparenchymal left pulmonary veins with secondary arteritis of the ipsilateral intraparenchymal pulmonary arteries. Atresia of the right or left main pulmonary veins or of the common pulmonary vein is a rare occurrence and it is believed that association of such with necrotizing pulmonary arteritis has never been reported. This case illustrates the potential consequences of severe pulmonary venous obstruction in the absence of a left to right shunt.

Progenipoietin-1: a multifunctional agonist of the granulocyte colony-stimulating factor receptor and fetal liver tyrosine kinase-3 is a potent mobilizer of hematopoietic stem cells.

OBJECTIVE: Progenipoietin-1 is an agonist of both the granulocyte colony-stimulating factor and fetal liver tyrosine kinase-3 receptors capable of inducing the proliferation of multiple hematopoietic cell lineages. The potential of progenipoietin-1 to mobilize transplantable hematopoietic stem cells into the peripheral blood was evaluated. METHODS: Cohorts of donor mice were treated with either progenipoietin-1, fetal liver tyrosine kinase-3 ligand, granulocyte colony-stimulating factor, or a vehicle control. Hematopoietic progenitor/stem-cell activity in donor blood was assayed by radioprotection, multilineage reconstitution, secondary transplantation, and competitive repopulation. RESULTS: Only 1 microL of peripheral blood from progenipoietin-1-treated donors was required to protect 80% of lethally irradiated mice, while in contrast 1 microL of peripheral blood from granulocyte colony-stimulating factor-treated donors failed to protect any recipients. The radioprotected recipients of progenipoietin-1-treated donor cells showed donor-derived (Ly5.2) multilineage hematopoietic reconstitution for up to 6 months. Serial transplantation studies using bone marrow from radioprotected, chimeric recipients demonstrated long-term donor-derived hematopoiesis, indicating the successful transplantation of multipotent hematopoietic stem cells. The engraftment potential of progenipoietin-1 donor-derived cells was directly compared with donors treated with granulocyte colony-stimulating factor or fetal liver tyrosine kinase-3 ligand alone or in combination. Both spleen colony-forming activity and competitive repopulating activity was highest in the blood from progenipoietin-1-treated donors. CONCLUSIONS: These studies demonstrate that progenipoietin-1 is a potent mobilizer of transplantable hematopoietic stem cells and indicate that this dual-receptor agonist has greater biologic activity than its constituent molecules.

Human growth hormone induces and maintains c-myc gene expression in Nb2 lymphoma cells.

The effect of human GH (hGH) on c-myc gene expression and cell proliferation in the Nb2 lymphoma cell line was examined. The addition of hormone to stationary cultures of Nb2 cells resulted in an increased accumulation of c-myc transcripts that was detectable within 15 min, reached a maximum induction of 25-fold in 3 h, and then gradually declined. Although maximal accumulation of c-myc transcripts occurred within 3 h after hGH addition, removal of the hormone even after 4 h of treatment resulted in a failure of the cells to proliferate. This loss of proliferative capacity following hormone removal was accompanied by a 20-fold reduction in the level of c-myc transcripts. These results indicate that hGH induced proliferation of Nb2 cells is associated with the induction and maintenance of c-myc gene expression.

Sustained hypertension in Dahl rats. Negative correlation of agonist response to blood pressure.

The perfused mesenteric vasculature of Dahl salt-sensitive rats on a high salt diet for 5 days (prehypertensive or early hypertensive) is selectively supersensitive to norepinephrine. The present goal was to determine whether that supersensitivity was maintained as hypertension developed. Littermates of salt-sensitive and salt-resistant rats (Dahl Brookhaven strain) were followed on low or high salt for up to 6 weeks. Systolic blood pressure was elevated in the salt-sensitive, high salt rats after 3 or 6 weeks but not after 5 days of the diet. The perfused mesenteric vascular beds from salt-sensitive rats were supersensitive to norepinephrine and nerve stimulation but not to potassium chloride when the rats had been maintained for 5 days or 3 weeks on the high salt diet. However, responses to norepinephrine declined after 6 weeks of the high salt diet. To determine whether sustained high blood pressure has a negative effect on mesenteric vascular responses, we conducted additional experiments with perfused mesenteric vascular beds from salt-sensitive Brookhaven (high salt, 5 weeks) and Rapp (high salt, 6 weeks) animals. Both groups exhibited significant negative correlations between in vivo systolic pressure and maximal responses of mesenteric vessels to norepinephrine and potassium chloride. We suggest that sustained hypertension in Dahl rats has a negative effect on the contractility of the mesenteric arterial system that, by 5 to 6 weeks, masks the initial supersensitivity to norepinephrine. No effects of any diet on the dilating responses of the mesenteric vessels to acetylcholine were observed in any group.

Sensitivity of caudal arteries and the mesenteric vascular bed to norepinephrine in DOCA-salt hypertension.

This study was undertaken to determine what factors might contribute to arterial supersensitivity to norepinephrine associated with deoxycorticosterone acetate (DOCA)-salt hypertension in the rat. Experimental groups of male rats were uninephrectomized and 1 week later began receiving twice weekly injections of DOCA (20 mg/kg s.c. in sesame oil) plus 1% NaCl and 0.2% KCl in their drinking water. For each experimental group, a group of age-matched male rats underwent a sham operation and received injections of sesame oil and the NaCl-KCl drinking water. Perfused caudal arteries from 3-week-hypertensive rats were supersensitive to intraluminal and extraluminal norepinephrine administration. However, this difference in sensitivity between hypertensive and control caudal arteries was demonstrable at low rates of perfusion, 0.5 to 1.0 ml/min, but not at rates of 2.0 to 2.6 ml/min. The supersensitivity was not due to differences in neuronal uptake or to inhibition of extraneuronal uptake by DOCA. The perfused mesenteric vascular bed from 3- or 6-week-hypertensive rats was also supersensitive to intraluminal norepinephrine. However, the demonstration of supersensitivity in the mesenteric vasculature was independent of perfusion rate (2.3-6.8 ml/min) and perfusion pressure in the range of 30 to 60 mm Hg. There was little or no supersensitivity to transmural nerve stimulation in either the caudal artery or the mesenteric vasculature, a finding consistent with the observed decrease in endogenous norepinephrine content. Microelectrodes were used to determine resting membrane potential in the smooth muscle cells. No differences in resting membrane potential were detected between caudal or mesenteric arteries from hypertensive compared with control rats 2, 3, or 6 weeks after initiation of the DOCA-salt regimen. It is concluded that 1) the perfusion rate is a critical factor in designing experiments to test the sensitivity of caudal arteries to drugs, 2) the perfused mesenteric vascular bed is a useful preparation for studying sensitivity of blood vessels in hypertension, 3) the supersensitivity of blood vessels in the DOCA-salt model may be of greater importance relative to circulating catecholamines than to sympathetic innervation, and 4) the supersensitivity of blood vessels to norepinephrine in the DOCA-salt model is not due to changes in neuronal uptake, extraneuronal uptake, or membrane potential of the vascular smooth muscle cells.