Sympathoadrenal Activation and Muscarinic Receptor Stimulation Induce Acute Release of Tissue-Type Plasminogen Activator but not von Willebrand Factor across the Human Forearm

Christina Jern; Lena Selin; Lilian Tengborn; Sverker Jern

doi:10.1055/s-0038-1657647

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 78(02): 887-891
DOI: 10.1055/s-0038-1657647

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Schattauer GmbH Stuttgart

Sympathoadrenal Activation and Muscarinic Receptor Stimulation Induce Acute Release of Tissue-Type Plasminogen Activator but not von Willebrand Factor across the Human Forearm

Christina Jern

¹The Clinical Experimental Research Laboratory, Heart-Lung Institute, Sahlgrenska University Hospital/Östra, Sahlgrenska University Hospital, Göteborg University, Gotebörg, Sweden

²Department of Neurology, Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Gotebörg University, Gotebörg, Sweden

,

Lena Selin

¹The Clinical Experimental Research Laboratory, Heart-Lung Institute, Sahlgrenska University Hospital/Östra, Sahlgrenska University Hospital, Göteborg University, Gotebörg, Sweden

,

Lilian Tengborn

³Coagulation Center, Institute of Internal Medicine, Sahlgrenska University Hospital, Göteborg University, Gotebörg, Sweden

,

Sverker Jern

¹The Clinical Experimental Research Laboratory, Heart-Lung Institute, Sahlgrenska University Hospital/Östra, Sahlgrenska University Hospital, Göteborg University, Gotebörg, Sweden

› Author Affiliations

Abstract

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Summary

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 from the endothelium is closely interrelated with release of von Willebrand factor (vWF). The aim of the present study was to simultaneously determine 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 |xg/min). Forearm blood flow was determined by venous occlusion plethysmography and interconverted to forearm plasma flow (FPF) using individual hematocrits. Net release/uptake rates 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 both t-PA antigen and activity. In contrast, there was no significant local net release of vWF antigen across the forearm. Net release rates of t-PA roughly doubled in response to the stress test (0.4 to 0.8 and 0.2 to 0.5 ng X min^-1X 100 ml^-1for t-PA antigen and activity, respectively, p <0.05 for both). Local administration of methacholine induced 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^-1X 100 ml^-1at the highest dose step for antigen and activity respectively, p <0.01 for both). In contrast, neither mental stress nor local administration of methacholine induced a significant net release of vWF antigen across the forearm. The results demonstrate that the processes of acute release of t-PA and vWF are not necessarily linked in vivo in man.

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References

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