Endothelial release of tissue-type plasminogen activator in the human forearm: role of nitric oxide.
Release of tissue-type plasminogen activator (t-PA) from the vascular endothelium is paramount to endogenous thrombolysis potential. In addition to its vasodilator effects, nitric oxide (NO) has important antithrombotic properties, such as inhibition of platelet aggregation. It is currently not clear whether NO influences the capacity of the endothelium to release t-PA. The authors determined whether net endothelial t-PA release is regulated, at least in part, by NO. Endothelial t-PA release was determined, in vivo, in response to intrabrachial infusions of bradykinin (12.5-50.0 ng.100 mL tissue-1.min-1) in the presence and absence of the NO synthase inhibitor, NG-monomethyl-l-arginine (l-NMMA; 5 mg/min) in 12 healthy men. Net release of t-PA across the forearm vascular bed was calculated as the product of arteriovenous concentration gradient and forearm plasma flow. The vasodilator response to bradykinin was significantly blunted ( approximately 30%) with l-NMMA. Although there was no effect of l-NMMA on basal t-PA release, acute release of t-PA to bradykinin was higher (P < 0.01) after (from -0.2 +/- 0.5 to 105.2 +/- 9.4 ng.100 mL tissue-1.min-1) versus before (from -0.4 +/- 0.7 to 48.7 +/- 7.3 ng.100 mL tissue-1.min-1) the administration of l-NMMA. Thus, in the absence of NO endothelial t-PA release was enhanced. These results suggest a potential regulatory influence of NO on bradykinin induced endothelial t-PA release.
Smith
Derek T
DT
Integrative Vascular Biology Laboratory, Department of Kinesiology and Integrative Physiology, University of Colorado, Boulder, CO 80309, U.S.A.
Hoetzer
Greta L
GL
Greiner
Jared J
JJ
Stauffer
Brian L
BL
DeSouza
Christopher A
CA
D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005542:Forearm; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010959:Tissue Plasminogen Activator