EFFECT OF ANGIOTENSIN-II RECEPTOR BLOCKADE ON FIBRINOLYSIS DURING ACUTE HYPERINSULINEMIA IN PATIENTS WITH ESSENTIAL-HYPERTENSION

We performed the present study to investigate indirectly the in vivo e ffects of angiotensin II on fibrinolysis and catecholamines by treatme nt with losartan, a selective angiotensin II type 1 receptor antagonis t. The effects were evaluated in basal conditions as well as in two di fferent models of acute hyperinsulinemia physiologically induced by or al glucose ingestion and by a euglycemic glucose clamp technique. Twen ty subjects with moderate hypertension were included in a randomized, double-blind, placebo-controlled crossover study of 4-week treatment p eriods. Plasma levels of catecholamines, activator activity and antige n, and plasminogen activator inhibitor type 1 activity and antigen wer e unchanged in the basal state after 4 weeks of treatment. During both models of hyperinsulinemia, plasminogen activator inhibitor activity and antigen decreased significantly (both P<.001), and tissue plasmino gen activator activity increased significantly (P<.01). Norepinephrine did not change during any of the procedures, whereas epinephrine incr eased significantly after 3 hours of the oral glucose tolerance test. Changes from baseline did not differ between the treatment and placebo regimens during the hyperinsulinemic procedures with regard to either of the fibrinolytic variables or the catecholamines. In conclusion, w e could not demonstrate any effects of 4 weeks of treatment with losar tan on plasma levels of fibrinolytic variables or catecholamines eithe r in basal conditions or during acute hyperinsulinemia. However, the p resent findings do not preclude more direct effects of angiotensin II or involvement of other receptor subtypes on fibrinolysis.