Recent studies implicate channels of the transient receptor potential vanilloid family (e.g., TRPV1) in regulating vascular tone; however, little is known about these channels in the coronary circulation. Furthermore, it is unclear whether metabolic syndrome alters the function and/or expression of TRPV1. We tested the hypothesis that TRPV1 mediates coronary vasodilation through endothelium-dependent mechanisms that are impaired by the metabolic syndrome. Studies were conducted on coronary arteries from lean and obese male Ossabaw miniature swine. In lean pigs, capsaicin, a TRPV1 agonist, relaxed arteries in a dose-dependent manner (EC50 = 116 +/- 41 nM). Capsaicin-induced relaxation was blocked by the TRPV1 antagonist capsazepine, endothelial denudation, inhibition of nitric oxide synthase, and K+ channel antagonists. Capsaicin-induced relaxation was impaired in rings from pigs with metabolic syndrome (91 +/- 4% vs. 51 +/- 10% relaxation at 100 microM). TRPV1 immunoreactivity was prominent in coronary endothelial cells. TRPV1 protein expression was decreased 40 +/- 11% in obese pigs. Capsaicin (100 microM) elicited divalent cation influx that was abolished in endothelial cells from obese pigs. These data indicate that TRPV1 channels are functionally expressed in the coronary circulation and mediate endothelium-dependent vasodilation through a mechanism involving nitric oxide and K+ channels. Impaired capsaicin-induced vasodilation in the metabolic syndrome is associated with decreased expression of TRPV1 and cation influx.
The vast boreal biome plays an important role in the global carbon cycle but is experiencing particularly rapid climate warming, threatening the integrity of valued ecosystems and their component species. We developed a framework and taxonomy to identify climate‐change refugia potential in the North American boreal region, summarizing current knowledge regarding mechanisms, geographic distribution, and landscape indicators. While “terrain‐mediated” refugia will mostly be limited to coastal and mountain regions, the ecological inertia (resistance to external fluctuations) contained in some boreal ecosystems may provide more extensive buffering against climate change, resulting in “ecosystem‐protected” refugia. A notable example is boreal peatlands, which can retain high surface soil moisture and water tables even in the face of drought. Refugia from wildfire are also especially important in the boreal region, which is characterized by active disturbance regimes. Our framework will help identify areas of high refugia potential, and inform ecosystem management and conservation planning in light of climate change.
In an intensive care-supported model of gram-negative septic shock, early AKI was not associated with changes in renal blood flow, oxygen delivery, or histological appearance. Other mechanisms must contribute to septic AKI.
The innovation of environmental policies and their subsequent diffusion throughout the American states has been the subject of significant academic attention. Using an event history analysis, a traditional geographic model for policy diffusion is tested against a model where states learn from peer groups, defined by political culture. There is evidence for state learning within peer groups but less support for diffusion across state borders. Policy characteristics, environmental conditions, economic resources, and political constraints and opportunities are tested as drivers of differences in policy adoption. More than any other factor, politics and political culture explains the adoption of energy and climate-change policies. These results also suggest that restricted models that test geographical mechanisms of policy diffusion likely omit important characteristics that are correlated across states, leading to biased findings regarding the geographical state diffusion models in the extant literature.
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