IN-VIVO RELEASE OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR ACROSS THE HUMANFOREARM DURING MENTAL STRESS

We have previously shown that plasma levels of endothelium-derived tis sue-type plasminogen activator (t-PA) increase during mental stress. T he aim of the study was to investigate in vivo release in an intact hu man muscle vascular bed. Eleven healthy young males (22-36 yrs) were s tudied at rest and during 10 min of mental stress (forced arithmetic). Net release or uptake were assessed by arterio-venous (AV) concentrat ion gradients across the forearm of t-PA antigen and t-PA activity, an d plasminogen activator inhibitor antigen type 1 (PAI-1). Forearm bloo d flow was measured by Venous occlusion plethysmography. At rest, ther e was a positive AV-difference of t-PA activity across the forearm ind icating a net release of t-PA activity of approximately 3.7 fmol x min (-1) X 100 ml(-1) (Wilcoxon's signed rank test vs 0, p = 0.01). Howeve r, t-PA antigen showed a variable release pattern. On the average, the re was a net release of 0.17 ng X min(-1) X 100 ml(-1) after 60 min of lest (Wilcoxon vs 0, p = 0.07). PAI-1 antigen showed net release at r est. In response to stress, forearm blood flow increased from 1.9 to 2 .9 ml x min(-1) X 100 ml(-1) (ANOVA, p = 0.007), and net release of t- PA activity increased to 9.8 fmol X min(-1) x 100 ml(-1) (ANOVA, p = 0 .01 compared with rest). Arterial and venous plasma t-PA levels al so increased significantly during stress (ANOVA, p <0.01). t-PA antigen s howed a similar but less pronounced release pattern during stress. PAI -1 antigen was unaffected by stress. During i.a. infusion of norepinep hrine (6-1,200 ng/min), forearm blood flow decreased from 2.1 till 1.0 ml X min(-1) x 100 ml(-1) (ANOVA, p = 0.002), while net release of t- PA activity increased from 2.7 till 10.1 fmol X min(-1) X 100 ml(-1) ( ANOVA, p = 0.002). The study demonstrates a net release of t-PA ac tiv ity across forearm tissues at rest. Net release of t-PA activity incre ases in response to mental stress and i.a, infusion of norepinephrine, despite disparate effects on blood flow.