Emerging trend in second messenger communication and myoendothelial feedback

Over the past decade, second messenger communication has emerged as one of the intriguing topics in the field of vasomotor control. Of particular interest has been the idea of second messenger flux from smooth muscle to endothelium initiating a feedback response that attenuates constriction. Mechanistic details of the precise signaling cascade have until recently remained elusive. In this perspective, we introduce readers to how myoendothelial gaps junctions could enable sufficient inositol trisphosphate flux to initiate endothelial Ca2+ events that activate Ca2+ sensitive K+ channels. The resulting hyperpolarizing current would in turn spreads back through the same myoendothelial gap junctions to moderate smooth muscle depolarization and constriction. In discussing this defined feedback mechanism, this brief manuscript will stress the importance of microdomains and of discrete cellular signaling

Association between active commuting and incident cardiovascular disease, cancer, and mortality: prospective cohort study

Objective: To investigate the association between active commuting and incident cardiovascular disease (CVD), cancer, and all cause mortality. Design: Prospective population based study. Setting: UK Biobank. Participants: 263 450 participants (106 674 (52%) women; mean age 52.6), recruited from 22 sites across the UK. The exposure variable was the mode of transport used (walking, cycling, mixed mode v non-active (car or public transport)) to commute to and from work on a typical day. Main outcome measures: Incident (fatal and non-fatal) CVD and cancer, and deaths from CVD, cancer, or any causes. Results: 2430 participants died (496 were related to CVD and 1126 to cancer) over a median of 5.0 years (interquartile range 4.3-5.5) follow-up. There were 3748 cancer and 1110 CVD events. In maximally adjusted models, commuting by cycle and by mixed mode including cycling were associated with lower risk of all cause mortality (cycling hazard ratio 0.59, 95% confidence interval 0.42 to 0.83, P=0.002; mixed mode cycling 0.76, 0.58 to 1.00, P<0.05), cancer incidence (cycling 0.55, 0.44 to 0.69, P<0.001; mixed mode cycling 0.64, 0.45 to 0.91, P=0.01), and cancer mortality (cycling 0.60, 0.40 to 0.90, P=0.01; mixed mode cycling 0.68, 0.57 to 0.81, P<0.001). Commuting by cycling and walking were associated with a lower risk of CVD incidence (cycling 0.54, 0.33 to 0.88, P=0.01; walking 0.73, 0.54 to 0.99, P=0.04) and CVD mortality (cycling 0.48, 0.25 to 0.92, P=0.03; walking 0.64, 0.45 to 0.91, P=0.01). No statistically significant associations were observed for walking commuting and all cause mortality or cancer outcomes. Mixed mode commuting including walking was not noticeably associated with any of the measured outcomes. Conclusions: Cycle commuting was associated with a lower risk of CVD, cancer, and all cause mortality. Walking commuting was associated with a lower risk of CVD independent of major measured confounding factors. Initiatives to encourage and support active commuting could reduce risk of death and the burden of important chronic conditions