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Dulaglutide underwent a major CV outcome trial as well, REWIND (2019) , which was noteworthy for including many patients without prior cardiovascular events (a primary prevention cohort)
If incubation with compounds is prolonged, superior efficacies can be reached: after 72 h exposure of NTS to compounds 1 and 6 had LD 50 s of 2.2 0.19 and 7.8 2.36 M respectively, whereas 2 had 0.18 0.007 M
This regulatory mechanism explains the so-called arginine paradox, which refers to the phenomenon where extracellular L-arginine availability influences NO production despite the saturation of NOS enzymes with intracellular arginine
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