Different effects of losartan and delapril on plasma PAI-1 levels in patients with mild to moderate hypertension.

ACE probably influences the fibrinolytic system at acentral point by converting angiotensin I to angiotensin II,which increases PAI-1 activity. This effect appears to bemediated via the AT1-receptor in humans. The RAAS mayalso contribute to a reduction in t-PA production by degra-dation of bradykinin, since the latter increases the release ofprostacyclin, nitric oxide, and t-PA from endothelial cells.Accordingly, ACE inhibitors not only influence the fibrino-lytic system by a reduction of PAI-1 activity but also byincreasing t-PA activity [1–3]. However, few studies haveanalysed the effects of AT1-R antagonists on t-PA and PAI-1plasma levels and the in vivo effects of AT1-R antagonistson the fibrinolytic system are conflicting [4,5]. We checkedin patients with mild to moderate hypertension the change int-PA and PAI-1 plasma levels after treatment with an AT1-Rantagonist and after treatment with an ACE-in. Thirtypatients, after a 14 day run-in period with placebo, wererandomised (double blind) in two groups: Group 1 (15patients) received an AT1-R antagonist (losartan 50 mgonce a day), Group 2 (15 patients) received an ACE-in(delapril 60 mg/day); 15 healthy subjects were chosen ascontrols. The diagnosis of essential hypertension was estab-lished by history and physical examination and by theabsence of clinical findings suggestive of a secondary formof hypertension. During the recruitment period all thepatients were totally unselected, and preliminary investiga-tions included routine biochemical tests (including clearanceof creatinine and oral glucose tolerance test), chest X-ray,standardand24hECGmonitoring,M-andB-modeechocardiography and fundus oculi examination. Patientswith myocardial infarction (within 3 months of the study),chest pain, heart block, valvular disease and heart failure),renal failure, type 1 or 2 diabetes mellitus, electrolyteimbalances, moderate or severe Keith-Wegener hyperten-sive retinopathy, alcoholism or psychiatric problems, andpatients with concomitant left ventricular hypertrophy(echocardiography criteria) or with other target organ dam-age were excluded. Each patient gave informed consent. Nopatient had to have previously received ACE-in or AT1-Rantagonists. Ten millimetres of blood was withdrawn andcollected into acidified buffered citrate (biopool stabilyte fort-PA assays) and citrate (monovette for PAI-1 assays tubes)and kept on ice before being centrifuged at 2000 g for 30min at 4 jC. Platelet-free plasma was decanted and stored at 80 jC before assay. Plasma PAI-1 and t-PA antigen weredetermined by ELISA and a photometric method. All theassays were performed by blinded independent. PAI-1 and t-PA plasma levels were checked at the end of the run-inperiod and after 6 months of treatment with losartan (group1) or delapril (group 2), as well as the biochemical tests. Allthe data were expressed as mean valuesFS.D. and com-pared by paired t-test and Kruskal–Wallis test. Table 1shows the clinical data of all the groups. After 6 months oflosartan and delapril treatment, a significant blood pressurereduction was observed in both the groups. At baseline thegroups 1 and 2 displayed significantly higher levels of PAI-1 and t-PA antigen than the control group (Table 2). Sixmonths of losartan treatment was associated with no signif-icant changes in PAI-1 and t-PA antigen levels. On the