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Thromb Haemost 1997; 78(02): 887-891
DOI: 10.1055/s-0038-1657647
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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
1   The Clinical Experimental Research Laboratory, Heart-Lung Institute, Sahlgrenska University Hospital/Östra, Sahlgrenska University Hospital, Göteborg University, Gotebörg, Sweden
2   Department of Neurology, Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Gotebörg University, Gotebörg, Sweden
,
Lena Selin
1   The Clinical Experimental Research Laboratory, Heart-Lung Institute, Sahlgrenska University Hospital/Östra, Sahlgrenska University Hospital, Göteborg University, Gotebörg, Sweden
,
Lilian Tengborn
3   Coagulation Center, Institute of Internal Medicine, Sahlgrenska University Hospital, Göteborg University, Gotebörg, Sweden
,
Sverker Jern
1   The Clinical Experimental Research Laboratory, Heart-Lung Institute, Sahlgrenska University Hospital/Östra, Sahlgrenska University Hospital, Göteborg University, Gotebörg, Sweden
› Author Affiliations
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Publication History

Received 03 1997

Accepted after revision 02 April 1997

Publication Date:
12 July 2018 (online)

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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.

 

  • References

  • 1 Emeis JJ. Mechanisms involved in short-term changes in blood levels of tissue-type plasminogen activator. In: Tissue-type Plasminogen Activator (t-PA): Physiological and Clinical Aspects. Kluft C. (ed). Boca Raton FL: CRC Press; 1988. 02. pp. 21-35
    Google Scholar
  • 2 Prowse CV, MacGregor IR. Regulation of the plasminogen activator level in blood. In: Tissue-type Plasminogen Activator (t-PA): Physiological and Clinical Aspects. Kluft C. (ed). Boca Raton FL: CRC Press; 1988. 02. pp. 49-65
    Google Scholar
  • 3 Wun T-C, Capuano A. Spontaneous fibrinolysis in whole human plasma. Identification of tissue activator-related protein as the major plasminogen activator causing spontaneous activity in vitro. J Biol Chem 1985; 260: 5061-5066
    PubMedGoogle Scholar
  • 4 Klöcking H-P. Release of plasminogen activator by acetylcholine from isolated perfused pig ear. Thromb Res 1979; 16: 261-264
    CrossrefPubMedGoogle Scholar
  • 5 Kitaguchi H, Hijikata A, Hirata M. Effect of thrombin on plasminogen activator release from isolated perfused dog leg. Thromb Res 1979; 16: 407-420
    CrossrefPubMedGoogle Scholar
  • 6 Nakajama K. Pharmacological observations of plasminogen activator release caused by vasoactive agents in isolated perfused pig ears. Thromb Res 1983; 29: 163-174
    PubMedGoogle Scholar
  • 7 Emeis JJ. Perfused rat hindlegs. A model to study plasminogen activator release. Thromb Res 1983; 30: 195-203
    CrossrefPubMedGoogle Scholar
  • 8 Tranquille N, Emeis JJ. The simultaneous acute release of tissue-type plasminogen activator and von Willebrand factor in the perfused rat hindleg region. Thromb Haemost 1990; 63: 454-458
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Pruis J, Emeis JJ. Endothelin-1 and -3 induce the release of tissue-plas-minogen activator and von Willebrand factor from endothelial cells. Eur J Pharmacol 1990; 187: 105-112
    CrossrefPubMedGoogle Scholar
  • 10 Tranquille N, Emeis JJ. On the role of calcium in the acute release of tissue-type plasminogen activator and von Willebrand factor from the perfused hindleg region. Thromb Haemost 1991; 66: 479-483
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Zhu GJ, Abbadini M, Donati MB, Mussoni L. Tissue-type plasminogen activator release in response to epinephrine in perfused rat hindlegs. Am J Physiol 1989; 256: H404-H10
    PubMedGoogle Scholar
  • 12 Eijnden-Schrauwen Y, Kooistra T, de VriesREM, Emeis JJ. Studies on the acute release of tissue-type plasminogen activator from human endothelial cells in vitro and in rats in vivo: evidence for a dynamic storage pool. Blood 1995; 85: 3510-3517
    CrossrefPubMedGoogle Scholar
  • 13 Cash JD, Woodfield DG, Allan AGE. Adrenergic mechanisms in the systemic plasminogen activator response to adrenaline in man. Br J Haematol 1970; 18: 487-494
    CrossrefPubMedGoogle Scholar
  • 14 Cash J, Gader AMA, Da CostaJ. The release of plasminogen activator and factor VIII by LVP, AVP, dDAVP, AT IE and OT in man. Br J Haematol 1974; 27: 363-364
    PubMedGoogle Scholar
  • 15 Mannucci PM, Åberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 1974; 30: 81-93
    PubMedGoogle Scholar
  • 16 Nilsson IM, Vilhardt H, Holmberg L, Åstedt B. Association between factor VIE related antigen and plasminogen activator. Acta Med Scand 1982; 211: 105-112
    PubMedGoogle Scholar
  • 17 Jem C, Eriksson E, Tengbom L, Risberg B, Wadenvik H, Jem S. Changes of plasma coagulation and fibrinolysis in response to mental stress. Thromb Haemost 1989; 62: 767-771
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Hansen J-B, Wilsegård L, Olsen JO, Osterud B. Formation and persistence of procoagulant and fibrinolytic activities in circulation after strenuous exercise. Thromb Haemost 1990; 64: 385-389
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Jem C, Manhem K, Eriksson E, Tengbom L, Risberg B, Jem S. Hemostatic responses to mental stress during the menstrual cycle. Thromb Haemost 1991; 66: 614-618
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Jem C, Selin L, Jem S. In vivo release of tissue-type plasminogen activator across the human forearm during mental stress. Thromb Haemost 1994; 72: 285-291
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Jem S, Selin L, Bergbrant A, Jem C. Release of tissue-type plasminogen activator in response to muscarinic receptor stimulation in human forearm. Thromb Haemost 1994; 72: 588-594
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Jaffe EA, Hoyer LW, Nachman RL. Synthesis of antihemophilic antigen by cultured human endothelial cells. J Clin Invest 1973; 52: 2757-2764
    CrossrefPubMedGoogle Scholar
  • 23 Mayadas T, Wagner DD, Simpson PJ. von Willebrand factor biosynthesis and partitioning between constitutive and regulated pathways of secretion after thrombin stimulation. Blood 1989; 73: 706-711
    CrossrefPubMedGoogle Scholar
  • 24 Wagner DD. The Weibel-Palade Body: the storage granule for von Willebrand factor and P-selectin. Thromb Haemost 1993; 70: 105-110
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Jem S. Effects of insulin on vascular responses to mental stress and norepinephrine in human forearm. Hypertension 1994; 24: 686-694
    CrossrefPubMedGoogle Scholar
  • 26 Rånby M, Nguyen G, Scarabin PY, Samama M. Immunoreactivity of tissue plasminogen activator and of its inhibitor complexes. Thromb Haemost 1989; 61: 409-414
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Petersen LC, Handest P, Brender J, Selmer J, Jørgensen M, Thorsen S. A sensitive solid-phase immunosorbent assay for tissue-type plasminogen activator activity in plasma. Using trinitrobenzoylated poly-D-lysin as a stimulator for plasminogen activation. Thromb Haemost 1987; 57: 205-211
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Ingerslev J. A sensitive ELISA for von Willebrand factor (vWf:Ag). Scand J Clin Lab Invest 1987; 47: 143-149
    CrossrefPubMedGoogle Scholar
  • 29 Vasey MW, Thayer JF. The continuing problem of false positives in repeated measures ANOVA in psychophysiology: A multivariate solution. Psychophysiol 1987; 24: 479-486
    CrossrefPubMedGoogle Scholar
  • 30 Wall RT, Counts RB, Harker LA, Striker GE. Binding and release of Factor VUI/von Willebrand’s factor by human endothelial cells. Br J Haematol 1980; 46: 287-298
    CrossrefPubMedGoogle Scholar
  • 31 Kjaeldgaard A, Kjaeldgaard M. In vitro stimulation of plasminogen activator release from vein walls by adrenaline. J Clin Pathol 1986; 39: 1241-1244
    CrossrefPubMedGoogle Scholar
  • 32 Tranquille N, Emeis JJ. The involvement of products of the phospholipase pathway in the acute release of tissue-type plasminogen activator. Eur J Pharmacol 1992; 213: 285-292
    CrossrefPubMedGoogle Scholar
  • 33 Hashemi S, Tackaberry ES, Palmer DS, Ganz PR. DD A VP-induced release of von Willebrand factor from endothelial cells in vitro: the effect of plasma and blood cells. Biochem Biophys Acta 1990; 1052: 63-70
    CrossrefPubMedGoogle Scholar
  • 34 Smalley DM, Fitzgerald JE, O’Rourke J. Adenosine diphosphate stimulates the endothelial release of tissue-plasminogen activator but not von Willebrand factor from isolated-perfused rat hind limbs. Thromb Haemost 1993; 70: 1043-1046
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Tranquille N, Emeis JJ. The role of cyclic nucleotides in the release of tissue-type plasminogen activator and von Willebrand factor. Thromb Haemost 1993; 69: 259-261
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 van den Eijnden-Schrauwen. gAcute release of tissue-type plasminogen activator from human endothelial cells. Dissertation, Gaubius Laboratory; Leiden: 1996
    Google Scholar