Assessing the barriers and facilitators of climate action planning in local governments: a two-round survey of expert opinion.

BACKGROUND: Climate change is one of the greatest threats to public health in this century. The UK is one of six countries that has enshrined in law a commitment to become net zero by 2050. However, there is a lack of guidance and structure for local government in the UK, which has responsibility for public health, to reach this goal and help their communities mitigate and adapt to the health and health inequality impacts of climate change. This study aimed to identify common barriers and facilitators related to addressing the health and health inequality impacts of climate change in local governments. METHODS: Using Normalisation Process Theory, we developed a two-round survey for people working in local authorities to identify the barriers and facilitators to including the health and health inequality impact of climate change in their climate action plans. The survey was delivered online via Qualtrics software. In the first-round respondents were able to express their views on barriers and facilitators and in the second round they ranked common themes identified from the first round. Two hundred and fifty people working in local government were invited to take part and n = 28 (11.2%) completed the first round of the survey and n = 14 completed the second round. Thematic analysis was used in Round 1 to identify common themes and weighted rankings were used to assess key barriers and facilitators in Round 2. RESULTS: Key facilitators were the need to save money on energy, and successful partnership working already in place including across local government, with local communities and external stakeholders. Key barriers were insufficient staff, resources and lack of support from management/leaders, and lack of local evidence. CONCLUSION: To mitigate and adapt to the health impacts of climate change, local government must nurture a culture of innovation and collaboration to ensure that different departments work together This means not just working with external partners, but also collaborating and co-producing with communities to achieve health equity and mitigate the debilitating effect of climate change on public health.

Temporal dynamics of sitting behavior at work.

Sitting for prolonged periods of time impairs people's health. Prior research has mainly investigated sitting behavior on an aggregate level, for example, by analyzing total sitting time per day. By contrast, taking a dynamic approach, here we conceptualize sitting behavior as a continuous chain of sit-to-stand and stand-to-sit transitions. We use multilevel time-to-event analysis to analyze the timing of these transitions. We analyze ∼30,000 objectively measured posture transitions from 156 people during work time. Results indicate that the temporal dynamics of sit-to-stand transitions differ from stand-to-sit transitions, and that people are quicker to switch postures later in the workday, and quicker to stand up after having been more active in the recent hours. We found no evidence for associations with physical fitness. Altogether, these findings provide insights into the origins of people's stand-up and sit-down decisions, show that sitting behavior is fundamentally different from exercise behavior, and provide pointers for the development of interventions.

A multi-component intervention to sit less and move more in a contact centre setting: a feasibility study.

BACKGROUND: Call agents spend ~ 90% of their working day seated, which may negatively impact health, productivity, and wellbeing. This study aimed to explore the acceptability and feasibility of a multi-component workplace intervention targeting increased activity and decreased prolonged sitting in the contact centre setting prior to a full-scale effectiveness trial. METHODS: An 8-week non-randomised pre-post feasibility study was conducted. Using a mixed methods approach, focus groups and interviews were thematically analysed to explore the acceptability and feasibility of key study phases, and provide context to agents' process evaluation and survey responses. The multi-component intervention, conducted in a single call centre, included height-adjustable workstations, emails, education and training sessions, and support from team leaders and a workplace champion. RESULTS: Six (of 20) team leaders were recruited, with 17 of 84 call agents (78% female, 39.3 ± 11.9 years) completing baseline assessments and 13 completing follow-up. High workload influenced recruitment. Call agents perceived assessments as acceptable, though strategies are needed to enhance fidelity. Education sessions, height-adjustable workstations and emails were perceived as the most effective components; however, height-adjustable hot-desks were not perceived as feasible in this setting. CONCLUSIONS: This study has identified unique, pragmatic considerations for conducting a multi-level, multi-component PA and SB intervention and associated evaluation in highly sedentary call agents in the challenging contact centre setting. The intervention was largely perceived positively, with call agents and team leaders describing numerous perceived positive effects on behavioural, health and work-related outcomes. Findings will be of value to researchers attempting to intervene in contact centres and will be used by the current authors to design a subsequent trial.

RhoA signaling through platelet P2Y1 receptor controls leukocyte recruitment in allergic mice.

BACKGROUND: Clinical studies reveal platelet activation in patients with asthma, allergic rhinitis, and eczema. This is distinct from platelet aggregation, which is critical for the maintenance of hemostasis and in which a role for platelet purinergic receptors is well documented. However, purines are also essential for inflammatory cell trafficking in animal models of allergic lung inflammation, which are known to be platelet dependent, yet the role of purines in the platelet activation accompanying inflammation is unknown. OBJECTIVES: We investigated whether the involvement of purine activation of platelets during allergic inflammation is distinct from purine involvement in platelet aggregation. METHODS: BALB/c mice were sensitized to ovalbumin and subsequent airway ovalbumin challenge. Bronchoalveolar lavage fluid was analyzed for inflammatory cells, and blood samples were assessed for platelet activation. The role of platelet purinergic receptors and associated signaling mechanisms (RhoA) were assessed. RESULTS: P2Y1, but not P2Y12 or P2X1, antagonism inhibited pulmonary leukocyte recruitment. The formation of platelet-leukocyte complexes in vivo and platelet/P-selectin-dependent polymorphonuclear cell migration in vitro were exclusively platelet P2Y1 receptor dependent. Furthermore, platelet P2Y1 activation resulted in RhoA activity in vivo after allergen challenge, and RhoA signaling in platelets through P2Y1 stimulation was required for platelet-dependent leukocyte chemotaxis in vitro. Leukocyte recruitment in thrombocytopenic mice remained suppressed after reinfusion of platelets pretreated with a P2Y1 antagonist or a Rho-associated kinase 1 inhibitor, confirming the crucial role of platelet P2Y1 receptor and subsequent activation of RhoA. CONCLUSION: RhoA signaling downstream of platelet P2Y1, but not P2Y12, represents a clear dichotomy in platelet activation during allergic inflammation versus hemostasis.

A systematic scoping review of health-promoting interventions for contact centre employees examined through a behaviour change wheel lens.

PURPOSE: Social determinants of health and poor working conditions contribute to excessive sickness absence and attrition in contact centre advisors. With no recent review conducted, the current scoping review is needed to investigate the volume, effectiveness, acceptability, and feasibility of health-promoting interventions for contact centre advisors. This will inform the adoption and implementation of evidence-based practice, and future research. METHODS: Searches conducted across four databases (MEDLINE, PsycInfo, CINAHL, Web of Science) and reference checking in February 2023 identified health-promoting interventions for contact centre advisors. Extracted and coded data from eligible interventions were systematically synthesised using the nine intervention functions of the Behaviour Change Wheel and behaviour change technique taxonomy. RESULTS: This scoping review identified a low number of high quality and peer-reviewed health-promoting intervention studies for contact centre advisors (28 studies since 2002). Most interventions were conducted in high-income countries with office-based advisors, predominantly using environmental restructuring and training strategies to improve health. Most interventions reported positive effectiveness results for the primary intended outcomes, which were broadly organised into: i) health behaviours (sedentary behaviour, physical activity, smoking); ii) physical health outcomes (musculoskeletal health, visual health, vocal health, sick building syndrome); iii) mental health outcomes (stress, job control, job satisfaction, wellbeing). Few interventions evaluated acceptability and feasibility. CONCLUSION: There is little evidence on the effectiveness, acceptability, and feasibility of health-promoting interventions for contact centre advisors. Evidence is especially needed in low-to-middle income countries, and for remote/hybrid, nightshift, older and disabled advisors.

Feeding ecology of monk sakis (Pithecia monachus) in a seasonally flooded forest in western Amazonia.

Sakis (genus Pithecia) are frugivorous primates with a preference for seeds that complete their diet with leaves and insects. Fruit pulp and seeds are known to have different nutritional characteristics that change during the process of ripening. The consumption of seeds can be an adaptation to changes in resource availability, as unripe seeds are a more steadily available resource than ripe pulp or young leaves. Here, we present the first study of the feeding ecology of monk sakis (Pithecia monachus). We investigated dietary composition and identified important feeding plants in a seasonally flooded forest within the Área de Conservación Regional Comunal Tamshiyacu-Tahuayo in Peruvian Amazonia. Throughout 20 months, we followed groups of monk sakis by foot and canoe and recorded 459 feeding events. Seeds were the most frequently consumed food item (49%), followed by pulp (mesocarp, pericarp or aril; 25%) and arthropods (22%). Leaves, bark, and flowers were ingested only sporadically. The importance of ripe seeds and arthropods in the diet of the monk sakis differed from other studies: we recorded the consumption of mostly ripe seeds and the share of arthropods was relatively high.

Evaluating the transduction efficiency of systemically delivered AAV vectors in the rat nervous system.

Gene delivery or manipulation with viral vectors is a frequently used tool in basic neuroscience studies. Adeno-associated viruses (AAV) are the most widely used vectors due to their relative safety and long-term efficacy without causing overt immunological complications. Many AAV serotypes have been discovered and engineered that preferentially transduce different populations of neurons. However, efficient targeting of peripheral neurons remains challenging for many researchers, and evaluation of peripheral neuron transduction with AAVs in rats is limited. Here, we aimed to test the efficiency of systemic AAVs to transduce peripheral neurons in rats. We administered AAV9-tdTomato, AAV-PHP.S-tdTomato, or AAV-retro-GFP systemically to neonatal rats via intraperitoneal injection. After 5 weeks, we evaluated expression patterns in peripheral sensory, motor, and autonomic neurons. No significant difference between the serotypes in the transduction of sensory neurons was noted, and all serotypes were more efficient in transducing NF200 + neurons compared to smaller CGRP + neurons. AAV-retro was more efficient at transducing motor neurons compared to other serotypes. Moreover, PHP.S was more efficient at transducing sympathetic neurons, and AAV-retro was more efficient at transducing parasympathetic neurons. These results indicate that specific AAV serotypes target peripheral neuron populations more efficiently than others in the neonatal rat.

A two-arm, randomised feasibility trial using link workers to improve dental visiting in people with severe mental illness: a protocol paper.

BACKGROUND: People with severe mental illness (e.g. psychosis, bipolar disorder) experience poor oral health compared to the general population as shown by more decayed, missing and filled teeth and a higher prevalence of periodontal disease. Attending dental services allows treatment of oral health problems and support for prevention. However, people with severe mental illness face multiple barriers to attending routine dental appointments and often struggle to access care. Link work interventions use non-clinical support staff to afford vulnerable populations the capacity, opportunity, and motivation to navigate use of services. The authors have co-developed with service users a link work intervention for supporting people with severe mental illness to access routine dental appointments. The Mouth Matters in Mental Health Study aims to explore the feasibility and acceptability of this intervention within the context of a feasibility randomised controlled trial (RCT) measuring outcomes related to the recruitment of participants, completion of assessments, and adherence to the intervention. The trial will closely monitor the safety of the intervention and trial procedures. METHODS: A feasibility RCT with 1:1 allocation to two arms: treatment as usual (control) or treatment as usual plus a link work intervention (treatment). The intervention consists of six sessions with a link worker over 9 months. Participants will be adults with severe mental illness receiving clinical input from secondary care mental health service and who have not attended a planned dental appointment in the past 3 years. Assessments will take place at baseline and after 9 months. The target recruitment total is 84 participants from across three NHS Trusts. A subset of participants and key stakeholders will complete qualitative interviews to explore the acceptability of the intervention and trial procedures. DISCUSSION: The link work intervention aims to improve dental access and reduce oral health inequalities in people with severe mental illness. There is a dearth of research relating to interventions that attempt to improve oral health outcomes in people with mental illness and the collected feasibility data will offer insights into this important area. TRIAL REGISTRATION: The trial was preregistered on ISRCTN (ISRCTN13650779) and ClinicalTrials.gov (NCT05545228).

Rise and Recharge: Exploring Employee Perceptions of and Contextual Factors Influencing an Individual-Level E-Health Smartphone Intervention to Reduce Office Workers' Sedentary Time at Work.

This feasibility study explored the contextual factors influencing office workers' adherence to an e-health intervention targeting total and prolonged sedentary time over 12 weeks. A three-arm quasi-randomized intervention included prompts at 30 or 60 min intervals delivered via a smartphone application, and a no-prompt comparison arm. Fifty-six office workers completed baseline (64% female) and 44 completed the 12 week follow-up (80% retention). Ecological momentary assessments (EMA) captured contextual data, with 82.8 ± 24.9 EMA prompt questionnaires completed weekly. Two focus groups with n = 8 Prompt 30 and 60 participants were conducted one-month post-intervention to address intervention acceptability and feasibility. Contextual findings indicate that when working on a sedentary task (i.e., reading or screen-based work) and located at an individual workstation, hourly prompts may be more acceptable and feasible for promoting a reduction in total and prolonged sedentary time compared to 30 min prompts. Interpersonal support also appears important for promoting subtle shifts in sedentary working practices. This novel study gives a real-time insight into the factors influencing adherence to e-health prompts. Findings identified unique, pragmatic considerations for delivering a workplace e-health intervention, indicating that further research is warranted to optimize the method of intervention delivery prior to evaluation of a large-scale intervention.

Sit Less and Move More-A Multicomponent Intervention With and Without Height-Adjustable Workstations in Contact Center Call Agents: A Pilot Randomized Controlled Trial.

OBJECTIVE: To pilot a multicomponent intervention to sit less and move more, with (SLAMM+) and without (SLAMM) height-adjustable workstations, in contact center call agents. METHODS: Agents were individually randomized to SLAMM or SLAMM+ in this 10-month, parallel, open-label, pilot trial. Mixed-methods assessed response, recruitment, retention, attrition and completion rates, adverse effects, trial feasibility and acceptability, preliminary effectiveness on worktime sitting, and described secondary outcomes. RESULTS: The participant recruitment rate, and randomization, data collection, and interventions were mostly acceptable. Refinements to organization recruitment were identified. High staff turnover negatively impacted retention and completion rates. The multicomponent intervention with height-adjustable workstations has potential to reduce sitting time at work. CONCLUSIONS: The demonstrated findings will help prepare for a future randomized controlled trial designed to assess the effect of the interventions.

Pharmacological characterisation of anti-inflammatory compounds in acute and chronic mouse models of cigarette smoke-induced inflammation.

BACKGROUND: Candidate compounds being developed to treat chronic obstructive pulmonary disease are typically assessed using either acute or chronic mouse smoking models; however, in both systems compounds have almost always been administered prophylactically. Our aim was to determine whether the prophylactic effects of reference anti-inflammatory compounds in acute mouse smoking models reflected their therapeutic effects in (more clinically relevant) chronic systems. METHODS: To do this, we started by examining the type of inflammatory cell infiltrate which occurred after acute (3 days) or chronic (12 weeks) cigarette smoke exposure (CSE) using female, C57BL/6 mice (n = 7-10). To compare the effects of anti-inflammatory compounds in these models, mice were exposed to either 3 days of CSE concomitant with compound dosing or 14 weeks of CSE with dosing beginning after week 12. Budesonide (1 mg kg-1; i.n., q.d.), roflumilast (3 mg kg-1; p.o., q.d.) and fluvastatin (2 mg kg-1; p.o., b.i.d.) were dosed 1 h before (and 5 h after for fluvastatin) CSE. These dose levels were selected because they have previously been shown to be efficacious in mouse models of lung inflammation. Bronchoalveolar lavage fluid (BALF) leukocyte number was the primary endpoint in both models as this is also a primary endpoint in early clinical studies. RESULTS: To start, we confirmed that the inflammatory phenotypes were different after acute (3 days) versus chronic (12 weeks) CSE. The inflammation in the acute systems was predominantly neutrophilic, while in the more chronic CSE systems BALF neutrophils (PMNs), macrophage and lymphocyte numbers were all increased (p < 0.05). In the acute model, both roflumilast and fluvastatin reduced BALF PMNs (p < 0.01) after 3 days of CSE, while budesonide had no effect on BALF PMNs. In the chronic model, therapeutically administered fluvastatin reduced the numbers of PMNs and macrophages in the BALF (p ≤ 0.05), while budesonide had no effect on PMN or macrophage numbers, but did reduce BALF lymphocytes (p < 0.01). Roflumilast's inhibitory effects on inflammatory cell infiltrate were not statistically significant. CONCLUSIONS: These results demonstrate that the acute, prophylactic systems can be used to identify compounds with therapeutic potential, but may not predict a compound's efficacy in chronic smoke exposure models.

Rise and Recharge: Effects on Activity Outcomes of an e-Health Smartphone Intervention to Reduce Office Workers' Sitting Time.

This feasibility study evaluated the effects of an individual-level intervention to target office workers total and prolonged sedentary behaviour during working hours, using an e-health smartphone application. A three-arm (Prompt-30 or 60 min Intervention arm and a No-Prompt Comparison arm), quasi-randomised intervention was conducted over 12 weeks. Behavioural outcomes (worktime sitting, standing, stepping, prolonged sitting, and physical activity) were monitored using accelerometers and anthropometrics measured at baseline, 6 weeks and 12 weeks. Cardiometabolic measures were taken at baseline and 12 weeks. Fifty-six office workers (64% female) completed baseline assessments. The Prompt-60 arm was associated with a reduction in occupational sitting time at 6 (-46.8 min/8 h workday [95% confidence interval = -86.4, -6.6], p < 0.05) and 12 weeks (-69.6 min/8 h workday [-111.0, -28.2], p < 0.05) relative to the No-Prompt Comparison arm. Sitting was primarily replaced with standing in both arms (p > 0.05). Both Intervention arms reduced time in prolonged sitting bouts at 12 weeks (Prompt-30: -27.0 [-99.0, 45.0]; Prompt-60: -25.8 [-98.4, 47.4] min/8 h workday; both p > 0.05). There were no changes in steps or cardiometabolic risk. Findings highlight the potential of a smartphone e-health application, suggesting 60 min prompts may present an optimal frequency to reduce total occupational sedentary behaviour.

Using an e-Health Intervention to Reduce Prolonged Sitting in UK Office Workers: A Randomised Acceptability and Feasibility Study.

Low-cost workplace interventions are required to reduce prolonged sitting in office workers as this may improve employees' health and well-being. This study aimed to assess the acceptability and feasibility of an e-health intervention to reduce prolonged sitting among sedentary UK-based office workers. Secondary aims were to describe preliminary changes in employee health, mood and work productivity after using an e-health intervention. Healthy, university office workers (n = 14) completed this study. An 8 week randomised crossover design was used, consisting of two trials: Intervention (computer-based prompts) and Control. Eligibility and retention rates were recorded to assess the feasibility of the trial and interviews were conducted following the intervention to explore its acceptability. Sitting, standing and stepping were objectively assessed prior to and during week 8 of each trial. Before and after each trial, measurements of vascular function, cerebrovascular function, mood and work productivity were obtained. This study had eligibility and retention rates of 54.5% and 77.8%, respectively. Participants expressed a lack of autonomy and disruption to their workflow when using the e-health intervention, raising concerns over its acceptability and long-term implementation. Preliminary data indicate that the intervention may improve the patterning of activity accrued during work hours, with increases in the number of standing and stepping bouts completed, in addition to improving vascular function. This e-health intervention is feasible to deliver in a cohort of university office workers. However, adaptations to its implementation, such as personalised settings, are needed to increase acceptability before larger trials can be conducted.

Comparison of cigarette smoke-induced acute inflammation in multiple strains of mice and the effect of a matrix metalloproteinase inhibitor on these responses.

The activities of proteases in the lung, specifically matrix metalloproteinases (MMPs), have been implicated in driving the inflammation and lung destruction observed in smokers with chronic obstructive pulmonary disease. Here, our aims were to compare the acute response with cigarette smoke exposure (CSE) in four mouse strains to identify common and distinguishing features and to assess the effect of an MMP inhibitor on this response. To do this, we exposed mice (BALB/C, C57BL/6, A/J, or 129/Sv) to whole-body CSE (1 h/day) for 3 days. CSE induced dose- and time-dependent increases in neutrophils and keratinocyte chemoattractant levels in the airways of all strains; however, the proportion of the neutrophilia differed among strains. In the two most contrasting strains, BALB/C and C57BL/6, we examined MMP gene expression and found only small changes apart from MMP-12, which was highly expressed in both strains. Both strains were then treated with a broad-spectrum MMP inhibitor, PKF242-484 [(2S,3R)-N(4)-((S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-N(1)-hydroxy-2-hydroxymethyl-3-(4-methoxy-phenyl)-succinimide] (0.5-10 mg/kg) either orally or intranasally 1 h before and 5 h after CSE for 3 days. PKF242-484 dose-dependently reduced neutrophilia in BALB/C mice when dosed orally (p < 0.01) or intranasally (p < 0.01) but had no clear effect in C57BL/6 by either route. PKF242-484 reduced BAL macrophages when dosed intranasally (p < 0.05) but had no dose-dependent effect when dosed orally in both strains. These data suggest the inflammation induced by CSE is similar, but not identical, in different mouse strains. In addition, the ability of broad-spectrum MMP inhibitors to inhibit smoke-induced acute neutrophil inflammation is strain-dependent, whereas its ability to limit macrophage infiltration may be route dependent.

Multi-Stakeholder Perspectives of Factors That Influence Contact Centre Call Agents' Workplace Physical Activity and Sedentary Behaviour.

Contact centre call agents are highly sedentary at work, which can negatively affect cardio-metabolic health. This qualitative cross-sectional study explored factors influencing call agents' workplace physical activity (PA) and sedentary behaviour (SB), and perspectives on strategies to help agents move more and sit less at work. Semi-structured interviews and focus groups with call agents (n = 20), team leaders (n = 11) and senior staff (n = 12) across four contact centres were guided by the socio-ecological model and analysed thematically. Agents offered insights into the impact of high occupational sitting and low PA on their physical and mental health, and factors influencing their motivation to move more and sit less at work. Team leaders, although pivotal in influencing behaviours, identified their own workload, and agents' requirement to meet targets, as factors influencing their ability to promote agents to move more and sit less at work. Further, senior team leaders offered a broad organisational perspective on influential factors, including business needs and the importance of return on investment from PA and SB interventions. Unique factors, including continuous monitoring of productivity metrics and personal time, a physical connection to their workstation, and low autonomy over their working practices, seemed to limit call agents' opportunity to move more and sit less at work. Proposed strategies included acknowledgement of PA and SB within policy and job roles, height-adjustable workstations, education and training sessions and greater interpersonal support. Additionally, measuring the impact of interventions was perceived to be key for developing a business case and enhancing organisational buy-in. Multi-level interventions embedded into current working practices appear important for the multiple stakeholders, while addressing concerns regarding productivity.

The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.

Heparanase is an endo-ß-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa-/-) mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa-/- and wild type (WT) control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa-/- mice displayed a significantly reduced eosinophil (but not neutrophil) recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD) found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

Evidence for sympathetic origins of hypertension in juvenile offspring of obese rats.

Maternal obesity in rodents is associated with increased adiposity, impaired glucose tolerance, and hypertension in adult offspring. In this study we investigated the influence of maternal obesity in the rat on blood pressure and blood pressure regulatory pathways in juvenile and adult offspring. Obesity was induced before pregnancy in female Sprague-Dawley rats by feeding a highly palatable energy-dense diet. In juvenile animals (30 days of age), before the onset of obesity and hyperleptinemia, basal nighttime mean arterial pressure was significantly raised in the offspring of obese dams (OffOb) relative to offspring of controls (OffCon; mean arterial pressure, males: OffOb, 121.8+/-0.6 mm Hg versus OffCon, 115.0+/-0.5 mm Hg, n=6, P<0.01; females: OffOb, 125.4+/-0.4 mm Hg versus OffCon, 114.4+/-0.5 mm Hg, n=6, P<0.001), as was the mean arterial pressure response to restraint stress (P<0.01). The pressor response to a leptin challenge was enhanced in OffOb rats (Deltamean arterial pressure: OffOb, 9.7+/-0.8 mm Hg versus OffCon, 5.3+/-1.3 mm Hg; n=8; P<0.05). Renal tissue norepinephrine content (P<0.001) and renin expression (P<0.05) were markedly raised. Analysis of heart rate variability revealed an increased low:high frequency ratio in OffOb versus OffCon rats (P<0.05). At 90 days, hypertension in OffOb rats persisted and was abolished by alpha1- and beta-adrenergic blockade, and cardiovascular responses to phenylephrine or sodium nitroprusside indicated altered baroreceptor function. The exaggerated pressor response to leptin in OffOb rats was maintained. Hypertension in the offspring of obese rats may arise from persistent sympathoexcitatory hyperresponsiveness acquired in early stages of development.