Short-term effects of exogenous angiotensin II on plasma fibrinolytic balance in normal subjects.
OBJECTIVE
Numerous studies have provided evidence for a direct functional link between the renin-angiotensin-aldosterone system and the fibrinolytic system. Angiotensin II has been suggested to mediate this interrelationship because this peptide was shown to stimulate plasminogen activator inhibitor-1 (PAI-1) in experimental settings. However, evidence from studies in man regarding effects of Angiotensin II on fibrinolytic function remains controversial.


METHODS
In the present study, we have therefore infused Angiotensin II at doses of 1, 3 and 10 ng kg(-1) min(-1), each over 45 min, in 9 healthy volunteer subjects without and with pretreatment with a single dose of the Angiotensin II (type 1) (AT1)-receptor antagonist valsartan (160 mg).


RESULTS
Angiotensin II infusion dose-dependently increased plasma Angiotensin II concentrations and systolic/diastolic arterial blood pressure from 121 +/- 2/70 +/- 2 mmHg to 146 +/- 2/97 +/- 1 mmHg (p < 0.001). The maximum increase in blood pressure was completely abolished (118 +/- 3/72 +/- 1 mmHg) when Angiotensin II was infused in volunteers pretreated with valsartan. In spite of the marked hemodynamic changes seen with the Angiotensin II infusion, no effect could be demonstrated on the activity and antigen concentration of PAI-1. Furthermore, pretreatment of the volunteers with valsartan markedly blunted the increase in arterial blood pressure but was not associated with changes in PAI-1.


CONCLUSIONS
In conclusion, in healthy volunteer subjects, short-term infusion of Angiotensin II without and with concomitant administration of an AT1-receptor antagonist has no effect on PAI-1 activities and plasma concentrations.
Lottermoser
Katja
K
Medizinische Universitäts-Poliklinik, Bonn, Germany.
Hertfelder
Hans-Jög
HJ
Gohlke
Peter
P
Vetter
Hans
H
Düsing
Rainer
R
D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage* / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D003971:Diastole / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000378:metabolism; D005858:Germany; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000008:administration & dosage; D012016:Reference Values; D012083:Renin / Q000187:drug effects / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D013599:Systole / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000378:metabolism; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068756:Valsartan; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000097:blood
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D044140:Receptor, Angiotensin, Type 1; D015842:Serine Proteinase Inhibitors; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000068756:Valsartan; D010959:Tissue Plasminogen Activator; D012083:Renin; D014633:Valine; D006854:Hydrocortisone