Endogenous nitric oxide contributes to bradykinin-stimulated glucose uptake but attenuates vascular tissuetype plasminogen activator release

Bradykinin causes vasodilation, stimulates tissue-type plas-minogen activator (t-PA) release and, in rodents, increases muscle glucose uptake. Although bradykinin causes vasodila-tion partly by activating nitric-oxide synthase (NOS), the role of nitric oxide in regulating bradykinin-stimulated t-PA release is uncertain. This study examined the effect of high-dose NOS inhibition on bradykinin-stimulated t-PA release and glucose uptake in humans. We studied 24 healthy (12 women and 12 men), overweight and obese (body mass index 25 kg/m2), normotensive, nondiabetic subjects with normal cholesterol. We measured the effect of intra-arterial N-monomethyl-L-ar-ginine (L-NMMA, 12 mol/min) on forearm blood flow (FBF), net t-PA release, and glucose uptake at baseline and in response to intra-arterial bradykinin (50–200 ng/min) in subjects pretreate