Student perceptions of the use of three-dimensional (3-D) virtual reality (VR) simulation in the delivery of radiation protection training for radiography and medical students.

BACKGROUND: VR simulation-based learning is increasingly used in healthcare education to prepare students for clinical practice. This study investigates healthcare students' experience of learning radiation safety in a simulated interventional radiology (IR) suite. METHOD: Radiography students (n = 35) and medical students (n = 100) were introduced to 3D VR radiation dosimetry software designed to improve the learners' understanding of radiation safety in IR. Radiography students underwent formal VR training and assessment, which was complemented with clinical placement. Medical students practiced similar 3D VR activities informally without assessment. An online questionnaire containing Likert questions and open-ended questions was used to gather student feedback on the perceived value of VR-based radiation safety education. Descriptive statistics and Mann-Whitney U tests were used to analyse Likert-questions. Open-ended question responses were thematically analysed. RESULTS: A survey response rate of 49% (n = 49) and 77% (n = 27) was obtained from radiography and medical students respectively. Most respondents (80%) enjoyed their 3D VR learning experience, favouring the in-person VR experience to online VR. 73% felt that VR learning enhanced their confidence across all relevant learning outcomes. Whilst confidence was enhanced across both cohorts, VR learning had a greater impact on confidence levels amongst medical students with respect to their understanding of radiation safety matters (U = 375.5, p < 0.01). 3D VR was deemed a valuable assessment tool. CONCLUSION: Radiation dosimetry simulation-based learning in the 3D VR IR suite is perceived to be a valuable pedagogical tool by radiography and medical students and enhances curricula content.

Vitamin D supplementation in pregnancy-a survey of compliance with recommendations.

BACKGROUND: Vitamin D deficiency in pregnancy has important maternal and fetal implications, with increased risk of developing gestational diabetes, preeclampsia, preterm birth and small for gestational age birthweight. It is recommended that every pregnant woman should take 5 µg (200 IU) of vitamin D per day during pregnancy and lactation. AIMS: This study aimed to determine the prevalence of women taking vitamin D supplementation and to identify the reasons for patients not taking supplementation within women attending an antenatal clinic in Dublin. METHODS: Survey of women attending the antenatal clinic of the National Maternity Hospital Dublin during 2 weeks in January 2017. Women were asked to record demographics, medical comorbidities and use of vitamin D supplementation or any other supplements in pregnancy, as well as reasons for non-use if appropriate. RESULTS: Three hundred women were invited to participate and 175 completed the questionnaire (58%). Overall, 38.9% (n = 68) reported to be taking vitamin D supplementation. Of the women that reported not to be taking vitamin D supplementation, 57.9% (n = 62) were taking a pregnancy multivitamin that contained vitamin D, and 28.0% (n = 30) did not know that it was recommended in pregnancy. Therefore, a total of 45 women (25.7%) in our cohort were taking no vitamin D supplementation during pregnancy. There was no difference in non-use based on maternal age, BMI, parity, or country of origin. CONCLUSIONS: Of the women surveyed, 74.3% reported supplementation with vitamin D, either knowingly or unknowingly. Public health initiatives need to utilize this relatively safe, low-cost intervention to maximize maternal and fetal health. This could reduce the rates of antenatal conditions with associated high morbidity and healthcare burden such as gestational diabetes and preeclampsia.

Peripheral i.v. analysis (PIVA) of venous waveforms for volume assessment in patients undergoing haemodialysis.

Background: The assessment of intravascular volume status remains a challenge for clinicians. Peripheral i.v. analysis (PIVA) is a method for analysing the peripheral venous waveform that has been used to monitor volume status. We present a proof-of-concept study for evaluating the efficacy of PIVA in detecting changes in fluid volume. Methods: We enrolled 37 hospitalized patients undergoing haemodialysis (HD) as a controlled model for intravascular volume loss. Respiratory rate (F0) and pulse rate (F1) frequencies were measured. PIVA signal was obtained by fast Fourier analysis of the venous waveform followed by weighing the magnitude of the amplitude of the pulse rate frequency. PIVA was compared with peripheral venous pressure and standard monitoring of vital signs. Results: Regression analysis showed a linear correlation between volume loss and change in the PIVA signal (R2=0.77). Receiver operator curves demonstrated that the PIVA signal showed an area under the curve of 0.89 for detection of 20 ml kg-1 change in volume. There was no correlation between volume loss and peripheral venous pressure, blood pressure or pulse rate. PIVA-derived pulse rate and respiratory rate were consistent with similar numbers derived from the bio-impedance and electrical signals from the electrocardiogram. Conclusions: PIVA is a minimally invasive, novel modality for detecting changes in fluid volume status, respiratory rate and pulse rate in spontaneously breathing patients with peripheral i.v. cannulas.

Randomised controlled trial of alternative messages to increase enrolment in a healthy food programme among individuals with diabetes.

OBJECTIVES: We compared the effectiveness of diabetes-focused messaging strategies at increasing enrolment in a healthy food programme among adults with diabetes. METHODS: Vitality is a multifaceted wellness benefit available to members of Discovery Health, a South Africa-based health insurer. One of the largest Vitality programmes is HealthyFood (HF), an incentive-based programme designed to encourage healthier diets by providing up to 25% cashback on healthy food purchases. We randomised adults with type 2 diabetes to 1 of 5 arms: (1) control, (2) a diabetes-specific message, (3) a message with a recommendation of HF written from the perspective of a HF member with diabetes, (4) a message containing a physician's recommendation of HF, or (5) the diabetes-specific message from arm 2 paired with an 'enhanced active choice'(EAC). In an EAC, readers are asked to make an immediate choice (in this case, to enrol or not enrol); the pros and cons associated with the preferred and non-preferred options are highlighted. HF enrolment was assessed 1 month following the first emailed message. RESULTS: We randomised 3906 members. After excluding those who enrolled in HF or departed from the Vitality programme before the first intervention email, 3665 (94%) were included in a modified intent-to-treat analysis. All 4 experimental arms had significantly higher HF enrolment rates compared with control (p<0.0001 for all comparisons). When comparing experimental arms, the diabetes-specific message with the EAC had a significantly higher enrolment rate (12.6%) than the diabetes-specific message alone (7.6%, p=0.0016). CONCLUSIONS: Messages focused on diabetes were effective at increasing enrolment in a healthy food programme. The addition of a framed active choice to a message significantly raised enrolment rates in this population. These findings suggest that simple, low-cost interventions can enhance enrolment in health promoting programmes and also be pragmatically tested within those programmes. TRIAL REGISTRATION NUMBER: NCT02462057.

Uptake of the Influenza Vaccination in Pregnancy.

Influenza is caused by a highly infectious RNA virus, which usually occurs in a seasonal pattern with epidemics in the winter months. The objective of this study was to determine the uptake of the influenza vaccine in a pregnant population and ascertain the reasons why some women did not receive it. A prospective cohort study was conducted over a two-week period in January 2016 in the National Maternity Hospital Dublin, a tertiary referral maternity hospital delivering over 9000 infants per year. There were 504 women studied over the 2-week period. Overall, 197(39.1%) women received the vaccine at a mean gestational age 20.9 weeks (SD 7.0). Given the increased rates of influenza in the community and the associated implications for mother and infant, it is important that pregnant women are educated regarding the risks of influenza in pregnancy and encourage this cohort to be vaccinated.

Transporting neonates with hypoxic-ischemic encephalopathy utilizing active hypothermia.

OBJECTIVE: The objective of this report was to evaluate a servo-controlled active hypothermia device used during the transport of neonates with HIE. STUDY DESIGN: Retrospective review of all cases of therapeutic hypothermia, both passive and active, using a servo-controlled device in a single regional referral neonatal intensive care unit from 2009-2013 RESULTS: An ambulance (43%), fixed wing aircraft (25%), or helicopter (32%) transported 28 neonates with active hypothermia. The servo-controlled device captured core temperatures in all 28 neonates, resulting in 2,985 minutes of data. All neonates attained a core temperature between 33-34 °C by 33 minutes of the transport. Once the neonates attained a core temperature, the average temperature for the remainder of the transport was 33 ± 0.2 °C. The neonates maintained the core temperature regardless of the type of transport vehicle. CONCLUSION: Servo-controlled hypothermia enables rapid attainment of targeted temperatures and maintains the temperature throughout the transport process in both ground and air transport.

Diversity-interaction modeling: estimating contributions of species identities and interactions to ecosystem function.

We develop a modeling framework that estimates the effects of species identity and diversity on ecosystem function and permits prediction of the diversity-function relationship across different types of community composition. Rather than just measure an overall effect of diversity, we separately estimate the contributions of different species interactions. This is especially important when both positive and negative interactions occur or where there are patterns in the interactions. Based on different biological assumptions, we can test for different patterns of interaction that correspond to the roles of evenness, functional groups, and functional redundancy. These more parsimonious descriptions can be especially useful in identifying general diversity-function relationships in communities with large numbers of species. We provide an example of the application of the modeling framework. These models describe community-level performance and thus do not require separate measurement of the performance of individual species. This flexible modeling approach can be tailored to test many hypotheses in biodiversity research and can suggest the interaction mechanisms that may be acting.

Biodiversity effects on yield and unsown species invasion in a temperate forage ecosystem.

BACKGROUND AND AIMS: Current agricultural practices are based on growing monocultures or binary mixtures over large areas, with a resultant impoverishing effect on biodiversity at several trophic levels. The effects of increasing the biodiversity of a sward mixture on dry matter yield and unsown species invasion were studied. METHODS: A field experiment involving four grassland species [two grasses--perennial ryegrass (Lolium perenne) and cocksfoot (Dactylis glomerata)--and two legumes--red clover (Trifolium pratense) and white clover (Trifolium repens)], grown in monocultures and mixtures in accordance with a simplex design, was carried out. The legumes were included either as single varieties or as one of two broad genetic-base composites. The experiment was harvested three times a year over three years; dry matter yield and yield of unsown species were determined at each harvest. Yields of individual species and interactions between all species present were estimated through a statistical modelling approach. KEY RESULTS: Species diversity produced a strong positive yield effect that resulted in transgressive over-yielding in the second and third years. Using broad genetic-base composites of the legumes had a small impact on yield and species interactions. Invasion by unsown species was strongly reduced by species diversity, but species identity was also important. Cocksfoot and white clover (with the exception of one broad genetic-base composite) reduced invasion, while red clover was the most invaded species. CONCLUSIONS: The results show that it is possible to increase, and stabilize, the yield of a grassland crop and reduce invasion by unsown species by increasing its species diversity.

Quality of life measurements and bronchodilator responsiveness in prescribing nebulizer therapy in COPD.

Nebulized bronchodilators are widely regarded as the optimal treatment for maintenance therapy in patients with severe chronic obstructive pulmonary disease (COPD). The aim of the study was to assess whether detailed physiological, functional and quality of life-related measurements can assist in determining the requirement for nebulized bronchodilator therapy in patients with moderate to severe COPD. This was an unblinded, randomized, crossover study that compared intermediate (120 mcg ipratropium bromide and 600 mcg of salbutamol using metered dose inhaler (MDI) and spacer) and high dose (nebulized 500 mcg ipratropium bromide and 2.5 mg salbutamol) bronchodilator therapy, on physiological, functional and quality of life-related measurements in patients with COPD. A total of 25 patients (12 female), mean (SD) age 68 (7) years, FEV(1) 45 (10) % predicted completed the study. There was no statistically significant difference between the treatments in the pre- and post-bronchodilator lung function values, six-minute walk distance, breathlessness score or quality of life questionnaires. Fifteen patients preferred bronchodilator therapy with nebulizer and 10 with MDI and spacer. In 20 patients at least one positive response in quality of life score, lung function or six-minute walk, was observed on the preferred treatment. Only a proportion of patients with moderate or severe COPD prefer nebulized bronchodilator therapy. This study found that none of the parameters singly or in combination were consistently predictive of patients' preference for nebulized bronchodilator therapy. Therefore, we suggest that clinicians institute a trial of stepping up to an intermediate dose of bronchodilators prior to introducing nebulized therapy.

[Sluggish cognitive tempo: symptoms of predominantly inattentive attention deficit hyperactivity disorder or a new clinical entity?]. / Tempo cognitivo lento: ¿síntomas del trastorno dedéficit de atención/hiperactividad predominantementedesatento o una nueva entidad clínica?

INTRODUCTION: The attention deficit/hyperactivity disorder (ADHD) is an heterogeneous entity with three accepted subtypes. This article reviews changes in the diagnostic criteria and controversies around the ADHD subtypes. DEVELOPMENT: We review the sluggish cognitive tempo, construct which has been associated with the ADHD predominantly inattentive subtype. We illustrate this construct through examining clinical cases that manifest 'sluggish cognitive tempo' symptoms. CONCLUSION: This article raises questions such as the utility of the sluggish cognitive tempo in the diagnosis of ADHD predominantly inattentive, and the possibility that it is a clinical entity not described up to the present date.

Tempo cognitivo lento: ¿síntomas del trastorno de déficit de atención/hiperactividad predominantemente desatento o una nueva entidad clínica? / Sluggish cognitive tempo: symptoms of predominantly inattentive attention deficit hyperactivity disorder or a new clinical entity?

Introducción. El trastorno de déficit de atención/hiperactividad(TDAH) es una entidad heterogénea en la cual se aceptanactualmente tres subtipos. Este artículo revisa los cambios en loscriterios diagnósticos del TDAH y las controversias surgidas alrededorde los subtipos. Desarrollo. Se revisa el constructo ‘tempocognitivo lento’ (sluggish cognitive tempo) que se ha asociado alsubtipo de TDAH predominantemente desatento. Se aportan ejemplosde casos clínicos cuyos síntomas se ajustan a la descripciónde tempo cognitivo lento. Conclusión. Se plantean cuestiones comola utilidad del tempo cognitivo lento en el diagnóstico del TDAHpredominantemente desatento, así como la posibilidad de que setrate de una entidad clínica no descrita hasta el momento

Introduction. The attention deficit/hyperactivity disorder (ADHD) is an heterogeneous entity with three acceptedsubtypes. This article reviews changes in the diagnostic criteria and controversies around the ADHD subtypes. Development. Wereview the sluggish cognitive tempo, construct which has been associated with the ADHD predominantly inattentive subtype. Weillustrate this construct through examining clinical cases that manifest ‘sluggish cognitive tempo’ symptoms. Conclusion. Thisarticle raises questions such as the utility of the sluggish cognitive tempo in the diagnosis of ADHD predominantly inattentive,and the possibility that it is a clinical entity not described up to the present date

[The neuropsychological phenotype of attention deficit hyperactivity disorder: are there differences among subtypes?]. / Fenotipo neuropsicológico del trastorno de déficit atencional/hiperactividad: existen diferencias entre los subtipos?

INTRODUCTION: Recent studies suggest that the ADHD subtypes would be best conceptualized as separate clinical entities, based on their epidemiology, central and associate symptomatology. OBJECTIVES: To determine the differences and similarities between subtypes in its associate symptomatology, specifically in the neuropsychological phenotype of executive dysfunction. PATIENTS AND METHODS: A group of children between 6 and 14 years of age with a diagnosis of ADHD-innattentive subtype (DESAT, n = 20) and another with ADHD-combined subtype (COMB, n = 39). RESULTS: Overall, the COMB subject sample displayed lower performance than DESAT group. Statistically significant differences were found in Kaufman-ABC-hands movement subtest, Wisconsin Card Sorting Test (WCST)-total error and WCST-conceptual level. CONCLUSIONS: The subtypes differ significantly in measures or non verbal working memory, hindsight, foresight, and motor control. Both groups share a deficit in response output speed and verbal working memory. We hypothesized areas of cognitive superiority for each subtype: spatial memory for the inattentive and gestaltic composition for the combined. Results provide evidence to support quantitative and qualitative differences in the neuropsychological profile between the ADHD-innatentive and combined subtypes.

PI3-kinase/Akt modulates vascular smooth muscle tone via cAMP signaling pathways.

Phosphatidylinositol 3-kinase (PI3-kinase) activates protein kinase B (also known as Akt), which phosphorylates and activates a cyclic nucleotide phosphodiesterase 3B. Increases in cyclic nucleotide concentrations inhibit agonist-induced contraction of vascular smooth muscle. Thus we hypothesized that the PI3-kinase/Akt pathway may regulate vascular smooth muscle tone. In unstimulated, intact bovine carotid artery smooth muscle, the basal phosphorylation of Akt was higher than that in cultured smooth muscle cells. The phosphorylation of Akt decreases in a time-dependent manner when incubated with the PI3-kinase inhibitor, LY-294002. Agonist (serotonin)-, phorbol ester (phorbol 12,13-dibutyrate; PDBu)-, and depolarization (KCl)-induced contractions of vascular smooth muscles were all inhibited in a dose-dependent fashion by LY-294002. However, LY-294002 did not inhibit serotonin- or PDBu-induced increases in myosin light chain phosphorylation or total O(2) consumption, suggesting that inhibition of contraction was not mediated by reversal or inhibition of the pathways that lead to smooth muscle activation and contraction. Treatment of vascular smooth muscle with LY-294002 increased the activity of cAMP-dependent protein kinase and increased the phosphorylation of the cAMP-dependent protein kinase substrate heat shock protein 20 (HSP20). These data suggest that activation of the PI3-kinase/Akt pathway in unstimulated smooth muscle may modulate vascular smooth muscle tone (allow agonist-induced contraction) through inhibition of the cyclic nucleotide/HSP20 pathway and suggest that cyclic nucleotide-dependent inhibition of contraction is dissociated from the myosin light chain contractile regulatory pathways.

The paradox of smooth muscle physiology.

Vascular smooth muscle tone is controlled by a balance between the cellular signaling pathways that mediate the generation of force (contraction) and the release of force (relaxation). The signaling events that activate contraction include Ca(2+)-dependent myosin light chain phosphorylation. The signaling events that mediate relaxation include the removal of a contractile agonist (passive relaxation) and activation of cyclic nucleotide-dependent signaling pathways in the continued presence of a contractile agonist (active relaxation). The major questions that remain in contractile physiology include (1) how is tonic force maintained when intracellular Ca(2+) levels and myosin light chain phosphorylation have returned to basal levels; and (2) what is the mechanism of cyclic nucleotide-dependent relaxation? This review focuses on these specific controversies surrounding the molecular mechanisms of contraction and relaxation of vascular smooth muscle.

How well do we care for patients with end stage chronic obstructive pulmonary disease (COPD)? A comparison of palliative care and quality of life in COPD and lung cancer.

BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD) have a poor quality of life and limited life expectancy. This study examined whether these patients were relatively disadvantaged in terms of medical and social care compared with a group with inoperable lung cancer. METHODS: An open two group comparison was made of 50 patients with severe COPD (forced expiratory volume in one second (FEV(1)) <0.75 l and at least one admission for hypercapnic respiratory failure) and 50 patients with unresectable non-small cell lung cancer (NSCLC). A multi-method design was used involving standardised quality of life tools, semi-structured interviews, and review of documentation. RESULTS: The patients with COPD had significantly worse activities of daily living and physical, social, and emotional functioning than the patients with NSCLC (p<0.05). The Hospital Anxiety and Depression Scale (HADS) scores suggested that 90% of patients with COPD suffered clinically relevant anxiety or depression compared with 52% of patients with NSCLC. Patients were generally satisfied with the medical care received, but only 4% in each group were formally assessed or treated for mental health problems. With regard to social support, the main difference between the groups was that, while 30% of patients with NSCLC received help from specialist palliative care services, none of the patients with COPD had access to a similar system of specialist care. Finally, patients in both groups reported a lack of information from professionals regarding diagnosis, prognosis and social support, although patients' information needs were disparate and often conflicting. CONCLUSION: This study suggests that patients with end stage COPD have significantly impaired quality of life and emotional well being which may not be as well met as those of patients with lung cancer, nor do they receive holistic care appropriate to their needs.

Stress causes decrease in vascular relaxation linked with altered phosphorylation of heat shock proteins.

Cyclic nucleotide-dependent vascular relaxation is associated with increases in the phosphorylation of a small heat shock protein (HSP), HSP20. An increase in phosphorylation of another small HSP, HSP27, is associated with impaired cyclic nucleotide-dependent vascular relaxation. Expression of HSPs is altered by exposure to several types of cellular stress in vitro. To determine if behavioral stress in vivo alters vascular expression and phosphorylation of the small HSPs and cyclic nucleotide-dependent vascular relaxation, borderline hypertensive rats were stressed by restraint and exposure to air-jet stress 2 h/day for 10 days or remained in their home cage. Stress impaired relaxation of aorta to forskolin, which activates adenylyl cyclase, and sodium nitroprusside, which activates guanylyl cyclase. This was associated with an increase in the aortic expression and phosphorylation of HSP27, which was localized to the vascular smooth muscle, but a decrease in the amount of phosphorylated (P)-HSP20. To determine if P-HSP27 inhibits phosphorylation of HSP20, P-HSP27 was added to a reaction mixture containing recombinant HSP20 and the catalytic subunit of cAMP-dependent protein kinase. P-HSP27 inhibited phosphorylation of HSP20 in a concentration-dependent manner. These data demonstrate that P-HSP27 can inhibit phosphorylation of HSP20. The increase in P-HSP27 and decrease in P-HSP20 were associated with reduced cyclic nucleotide-dependent vascular smooth muscle relaxation in response to behavioral stress in vivo, an effect similar to that observed previously in response to cellular stress in vitro.

The macromolecular associations of heat shock protein-27 in vascular smooth muscle.

BACKGROUND: Behavioral stress is a risk factor for hypertension and atherosclerosis. Stress leads to increases in the expression and phosphorylation of heat shock proteins (HSPs) in vascular smooth muscle. Two small heat shock proteins, HSP27 and HSP20, have been implicated in the regulation of the contraction and relaxation of smooth muscle. We hypothesized that stress-induced alterations in the phosphorylation of HSP27 would effect the macromolecular associations of the small HSPs. METHODS: Bovine carotid artery smooth muscle was treated with buffer alone or with the chemical stressor, arsenite. HSP27 phosphorylation was determined with isoelectric focusing immunoblotting. Macromolecular interactions were determined with subcellular fractionation, molecular sieving, and glutaraldehyde cross-linking and immunoblotting. RESULTS: Arsenite treatment led to increases in the phosphorylation of HSP27, a redistribution of some HSP27 from a cytosolic to a particulate fraction and to the formation of larger macromolecular aggregates of HSP27. Glutaraldehyde cross-linking and immunoblotting demonstrated that HSP27 existed in monomeric and dimeric forms, which suggested that the large aggregates were not simply aggregates of HSP27 but contained other proteins. CONCLUSIONS: Cellular stress leads to increases in the phosphorylation of HSP27 and to changes in the macromolecular associations of HSP27 in intact vascular smooth muscles. The functions of the small HSPs in the vascular smooth muscle may be dependent on both phosphorylation and macromolecular associations.

Early experience with infectious complications of percutaneous femoral artery closure devices.

Percutaneous femoral artery closure devices are being used routinely after cardiac catheterizations. The use of these devices has been advocated to decrease length of stay, promote early ambulation, and prevent bleeding. We reviewed the use of these devices in our institution and report three cases of infectious complications (two pseudoaneurysms and one infected hematoma). Reports of infected pseudoaneurysms after cardiac catheterization before the implementation of these devices are rare. The use of these devices may be associated with an increased incidence of infected femoral pseudo-aneurysms.

Functional expression of NOS 1 in vascular smooth muscle.

Substances that increase intracellular calcium concentration ([Ca(2+)](i)), such as serotonin, are known to induce vascular smooth muscle (VSM) contraction. However, increases in [Ca(2+)](i) also activate Ca(2+)/calmodulin-dependent nitric oxide synthases (NOS), which leads to increases in cGMP and activation of cGMP-dependent protein kinase (PKG). One recently identified substrate protein of PKG is the small heat shock protein, HSP20. The purpose of this study was to determine if serotonin activates a Ca(2+)-dependent NOS in VSM. Strips of bovine carotid arterial smooth muscle denuded of endothelium were stimulated with serotonin in the presence and absence of the nonspecific NOS inhibitor N-monomethyl-L-arginine (L-NMMA). Activation of NOS was determined by increases in cGMP and in the phosphorylation of HSP20. Immunohistochemical and Western blotting techniques were performed to identify specific NOS isoforms in bovine carotid arterial smooth muscle preparations. Serotonin stimulation led to significant increases in cGMP and in the phosphorylation of HSP20, which were inhibited by pretreatment with L-NMMA. Antibodies against NOS 1 stained the media of bovine carotid and human renal arteries, whereas antibodies against NOS 3 stained only the endothelium. Additionally, the conversion of radiolabeled L-arginine to L-citrulline NOS activity demonstrated a consistent amount of activity present in the endothelium-denuded smooth muscle preparations that was reduced by 99% with an NOS 1 specific inhibitor. Finally, an NOS 1 specific inhibitor, 7-nitroindazole, augmented contractions induced by high extracellular KCl. This study demonstrates that NOS 1 is present in VSM and may effect physiological contractile responses.

Cellular stress inhibits vascular smooth muscle relaxation.

PURPOSE: Cellular stress has been shown to induce a group of proteins called heat shock proteins (HSPs). Recent evidence suggests that a group of small HSPs may modulate vascular smooth muscle contraction (HSP27) and/or relaxation (HSP20). In this investigation, we hypothesized that cellular stress would alter contraction and/or relaxation of intact vascular smooth muscles and would lead to changes in the induction and/or phosphorylation of the small HSPs. METHODS: Bovine carotid arteries were obtained from an abattoir, and physiologic contractile responses were determined in a muscle bath. Phosphorylation state-specific antibodies were produced and characterized against HSP27. Phosphorylation events were determined with phosphorylation state-specific antibodies or whole-cell phosphorylation and two-dimensional gel electrophoresis. RESULTS: Cellular stress induced by arsenite or heat shock did not alter basal tone or the magnitude of contractions induced by serotonin or high extracellular potassium chloride. However, cellular stress led to inhibition of forskolin and sodium nitroprusside-induced vasorelaxation. This impaired vasorelaxation was associated with increases in the phosphorylation of HSP27 and decreases in forskolin-induced phosphorylation of HSP20. CONCLUSION: Cellular stress, which leads to increases in the phosphorylation of HSP27, inhibits cyclic nucleotide-dependent vascular relaxation and cyclic nucleotide-dependent increases in the phosphorylation of HSP20.