SYMPATHOADRENAL ACTIVATION AND MUSCARINIC RECEPTOR STIMULATION INDUCEACUTE RELEASE OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR BUT NOT VON-WILLEBRAND-FACTOR ACROSS THE HUMAN FOREARM

We have previously shown that both mental stress and administration of the muscarinic receptor agonist methacholine induce an acute release of tissue-type plasminogen activator (t-PA) across the human forearm. There are data indicating that the regulated acute release of t-PA fro m the endothelium is closely interrelated with release of von Willebra nd factor (vWF). The aim of the present study was to simultaneously de termine basal and stimulated in vivo release rates of t-PA and vWF in an intact human muscle vascular bed. Eighteen healthy young males were studied at rest and during 10 min of mental stress (forced arithmetic ). A subsample of ten subjects also received a stepwise i.a. infusion of methacholine (0.1-0.8-4.0 mu g/min). Forearm blood flow was determi ned by venous occlusion plethysmography and interconverted to forearm plasma flow (FPF) using individual hematocrits. Net release/uptake rat es of t-PA and vWF were calculated as the product of the arteriovenous concentration gradient and FPF. At rest there was a net release of bo th t-PA antigen and activity. In contrast, there was no significant lo cal net release of VWF antigen across the forearm. Net release rates o f t-PA roughly doubled in,response to the stress test (0.4 to 0.8 and 0.2 to 0.5 ng X min(-1) X 100 ml(-1) for t-PA antigen and activity, re spectively, p <0.05 for both). Local administration of methacholine in duced a more than 10-fold increase in the net release rates of t-PA (0 .6 to 9.6 and 0.3 to 6.6 ng X min(-1) X 100 ml(-1) at the highest dose step for antigen and activity respectively, p <0.01 for both). fn con trast, neither mental stress nor local administration of methacholine induced a significant net release of VWF antigen across the forearm. T he results demonstrate that the processes of acute release of t-PA and VWF are not necessarily linked in vivo in man.