The basal NO production in the cardiovascular system was then determined as change in AIx during NO synthase blockade with N(G)-monomethyl-L-arginine (L-NMMA, 3.25 mg/kg). Results: AIx increased Daporinad from 17.5 +/- 14.6 to 23.1 +/- 14.2 during L-NMMA infusion (p < 0.001). The increase in AIx during NO synthase blockade, an index of basal NO production, was inversely related to baseline central AIx and PP, and positively to PP amplification. Multiple linear regression analyses disclosed that in addition to age and mean blood pressure, change of AIx to L-NMMA is a strong and independent determinant of baseline central AIx, central PP and PP amplification. Conclusion:

Greater change of AIx to L-NMMA, an index of basal NO production, is associated with better large-artery function. Therefore, therapeutic interventions which increase the basal NO production might be particularly effective in reducing cardiovascular risk. Copyright (C) 2010 S. Karger AG, Basel”
“The vesicular CB-839 chemical structure monoamine transporter type 2 (VMAT2) is highly expressed in pancreatic beta-cells and thus has been proposed to be a potential target for measuring beta-cell mass (BCM) by molecular imaging. C-11- and F-18-labeled tetrabenazine derivatives

targeting VMAT2 have shown some promising results as potential biomarkers for BCM. In the present study, we examined the binding characteristics of 9- fluoropropyl-(+)-dihydrotetrabenzazine ([(18)F]AV-133), a potential PET tracer for BCM imaging, in rat pancreas and rat brain.

Methods: Pancreatic exocrine cells and pancreatic islet cells were isolated and purified from Sprague-Dawley rats. Membrane homogenates, PD-1/PD-L1 Inhibitor 3 ic50 prepared from both pancreatic exocrine and islet cells as well as from brain striatum and hypothalamus regions, were used for in vitro binding studies. In vitro and ex vivo autoradiography studies with [(18)F]AV-133 were performed on rat brain and rat pancreas sections. lmmunohistochemistry studies were performed to confirm the distribution of VMAT2 on islet beta-cells.

Results: Excellent binding affinities

of [(18)F]AV-133 were observed in rat striatum and hypothalamus homogenates with K(d) values of 0.19 and 0.25 nM, respectively. In contrast to single-site binding observed in rat striatum homogenates, rat islet cell homogenates showed two saturable binding sites (site A: K(d)=6.76 nM, B(max)=60 fmol/mg protein; site B: K(d)=241 nM, B(max)=1500 fmol/mg protein). Rat exocrine pancreas homogenates showed only a single low-affinity binding site (K(d)=209 nM), which was similar to site B in islet cells. In vitro autoradiography of [(18)F]AV-133 using frozen sections of rat pancreas showed specific labeling of islets, as evidenced by co-localization with anti-insulin antibody. Ex vivo VMAT2 pancreatic autoradiography in the rat, however, was not successful, in contrast to the excellent ex vivo autoradiography of VMAT2 binding sites in the brain.