Description: Background The expression of calcium/calmodulin-dependent kinase IV (CaMKIV) was hitherto thought to be confined to the nervous system. However, a recent genome-wide analysis indicated an association between hypertension and a single-nucleotide polymorphism (rs10491334) of the human CaMKIV gene ( CaMK4 ) , which suggests a role for this kinase in the regulation of vascular tone. Methods and Results To directly assess the role of CaMKIV in hypertension, we characterized the cardiovascular phenotype of CaMK4 –/– mice. They displayed a typical hypertensive phenotype, including high blood pressure levels, cardiac hypertrophy, vascular and kidney damage, and reduced tolerance to chronic ischemia and myocardial infarction compared with wild-type littermates. Interestingly, in vitro experiments showed the ability of this kinase to activate endothelial nitric oxide synthase. Eventually, in a population study, we found that the rs10491334 variant associates with a reduction in the expression levels of CaMKIV in lymphocytes from hypertensive patients. Conclusions Taken together, our results provide evidence that CaMKIV plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity.

Description: Photolytic production rates of NO, NO2 and OH radicals in snow and the total absorption spectrum due to impurities in snowpack have been calculated for the Ocean-Atmosphere-Sea-Ice-Snowpack (OASIS) campaign during Spring 2009 at Barrow, Alaska. The photolytic production rate and snowpack absorption cross-sections were calculated from measurements of snowpack stratigraphy, light penetration depths (e-folding depths), nadir reflectivity (350–700 nm) and UV broadband atmospheric radiation. Maximum NOx fluxes calculated during the campaign owing to combined nitrate and nitrite photolysis were calculated as 72 nmol m−2 h−1 for the inland snowpack and 44 nmol m−2 h−1 for the snow on sea-ice and snowpack around the Barrow Arctic Research Center (BARC). Depth-integrated photochemical production rates of OH radicals were calculated giving maximum OH depth-integrated production rates of ∼160 nmol m−2 h−1 for the inland snowpack and ∼110–120 nmol m−2 h−1 for the snow around BARC and snow on sea-ice. Light penetration (e-folding) depths at a wavelength of 400 nm measured for snowpack in the vicinity of Barrow and snow on sea-ice are ∼9 cm and 14 cm for snow 15 km inland. Fitting scaled HULIS (HUmic-LIke Substances) and black carbon absorption cross-sections to the determined snow impurity absorption cross-sections show a “humic-like” component to snowpack absorption, with typical concentrations of 1.2–1.5 μgC g−1. Estimates of black carbon concentrations for the four snowpacks are ∼40 to 70 ng g−1 for the terrestrial Arctic snowpacks and ∼90 ng g−1 for snow on sea-ice.

Description: Recently it has been demonstrated that catecholamines are produced and used by macrophages and mediate immune response. The aim of this study is to verify whether endothelial cells (ECs), which are of myeloid origin, can produce catecholamines. We demonstrated that genes coding for tyrosine hydroxylase, Dopa decarboxylase, dopamine β hydroxylase (DβH), and phenylethanolamine- N -methyl transferase, enzymes involved in the synthesis of catecholamines, are all expressed in basal conditions in bovine aorta ECs, and their expression is enhanced in response to hypoxia. Moreover, hypoxia enhances catecholamine release. To evaluate the signal transduction pathway that regulates catecholamine synthesis in ECs, we overexpressed in bovine aorta ECs either protein kinase A (PKA) or the transcription factor cAMP response element binding, because PKA/cAMP response element binding activation induces tyrosine hydroxylase transcription and activity in response to stress. Both cAMP response element binding and PKA overexpression enhance DβH and phenylethanolamine- N -methyl transferase gene expression and catecholamine release, whereas H89, inhibitor of PKA, exerts the opposite effect, evidencing the role of PKA/cAMP response element binding transduction pathway in the regulation of catecholamine release in bovine aorta ECs. We then evaluated by immunohistochemistry the expression of tyrosine hydroxylase, Dopa decarboxylase, DβH, and phenylethanolamine- N -methyl transferase in femoral arteries from hindlimbs of C57Bl/6 mice 3 days after removal of the common femoral artery to induce chronic ischemia. Ischemia evokes tyrosine hydroxylase, Dopa decarboxylase, DβH, and phenylethanolamine- N -methyl transferase expression in the endothelium. Finally, the pharmacological inhibition of catecholamine release by fusaric acid, an inhibitor of DβH, reduces the ability of ECs to form network-like structures on Matrigel matrix. In conclusion, our study demonstrates for the first time that ECs are able to synthesize and release catecholamines in response to ischemia.