Angiotensin II infusion in man is proinflammatory but has no short-term effects on thrombin generation in vivo.
BACKGROUND
Angiotensin (Ang) II may be involved in the development of cardiovascular disease. We examined the potential proinflammatory and prothrombotic effects of Ang II in 16 healthy subjects and in 16 subjects with familial combined hyperlipidemia (FCHL), a condition associated with an increased risk of cardiovascular complications.


METHODS
We studied the effects of a three hour intravenous infusion of Ang II (10 ng/kg/min) on plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), circulating leukocyte count, tissue plasminogen activator/plasminogen activator inhibitor-1 (t-PA/PAI-1) complexes, prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin (TAT) complexes. Blood was collected before, during and 1 h after Ang II infusion.


RESULTS
IL-6 was higher in subjects with FCHL at rest (P < 0.05) and increased (P < 0.001) similarly in both groups by Ang II infusion. Also leukocyte count was higher in subjects with FCHL at rest (P < 0.001) and increased (P < 0.001) similarly in both groups by Ang II infusion. T-PA/PAI-1 complexes were higher in subjects with FCHL at rest (P < 0.001) and decreased (P < 0.001) similarly in both groups during Ang II infusion. TNF-alpha, F1+2 and TAT complexes were similar in the two groups at rest and did not change during or after the Ang II infusion.


CONCLUSIONS
A three hour Ang II infusion increases inflammation and may enhance fibrinolysis but does not affect short term thrombin generation. Subjects with FCHL have signs of increased inflammation and impaired fibrinolysis.
Ekholm
M
M
Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden. mikael.ekholm@ki.se
Kahan
T
T
Jörneskog
G
G
Bröijersen
A
A
Wallén
N H
NH
D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000991:Antithrombins / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced*; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011516:Prothrombin; D013917:Thrombin / Q000096:biosynthesis* / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000991:Antithrombins; D015850:Interleukin-6; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; C045879:prothrombin fragment 1.2; D000804:Angiotensin II; D011516:Prothrombin; D013917:Thrombin; D010959:Tissue Plasminogen Activator