Local tissue factor pathway inhibitor release in the human forearm.
Nineteen healthy men received unilateral brachial artery infusions of either unfractioned heparin (0.3-100 IU/min), saline or the endothelium-dependent vasodilators substance P (2-8 pmol/min) and bradykinin (100-1000 pmol/min), and the endothelium-independent vasodilator sodium nitroprusside (2-8 micro g/min). Heparin caused a dose-dependent increase in plasma TFPI concentrations in both arms (ANOVA, p <0.0001). Estimated net forearm TFPI release was 7 +/- 16, 29 +/- 20 and 138 +/- 72 ng/100 mL tissue/min during 10, 30 and 100 IU/min of heparin respectively (ANOVA, p <0.0001). Compared to the systemic circulation, the forearm sensitivity to heparin induced TFPI release was 3.6-fold lower (166 +/- 67 ng/IU vs. 596 +/- 252 ng/IU: t-test, p = 0.004). Substance P, bradykinin and sodium nitroprusside all caused substantial dose-dependent increases in blood flow (ANOVA, p <0.001 for all) without affecting plasma TFPI concentrations. There are important regional differences in endothelial TFPI release, with the forearm circulation being relatively insensitive to heparin.
Kemme
Michiel J B
MJ
Centre for Human Drug Research, Zernikedreef 10, 2333 CL Leiden, The Netherlands. mk@CHDR.nl
Burggraaf
Jacobus
J
Schoemaker
Rik C
RC
Cohen
Adam F
AF
Kluft
Cornelis
C
Chia
Stanley
S
Webb
David J
DJ
Newby
David E
DE
D000328:Adult; D001920:Bradykinin / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005542:Forearm; D006439:Hemodynamics / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007261:Infusions, Intra-Arterial; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D009599:Nitroprusside / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage
D008074:Lipoproteins; D014665:Vasodilator Agents; C051928:lipoprotein-associated coagulation inhibitor; D009599:Nitroprusside; D013373:Substance P; D006493:Heparin; D001920:Bradykinin