title: Role of angiotensin II in plasma PAI-1 changes induced by imidapril or candesartan in hypertensive patients with metabolic syndrome.
abstract: To evaluate the relationship between plasma plasminogen activator inhibitor-1 (PAI-1) and angiotensin II (Ang II) changes during treatment with imidapril and candesartan in hypertensive patients with metabolic syndrome. A total of 84 hypertensive patients with metabolic syndrome were randomized to imidapril 10 mg or candesartan 16 mg for 16 weeks. At weeks 4 and 8, there was a dose titration to imidapril 20 mg and candesartan 32 mg in nonresponders (systolic blood pressure (SBP) >140 and/or diastolic blood pressure (DBP) >90 mm Hg). We evaluated, at baseline and after 2, 4, 8, 12 and 16 weeks, clinic blood pressure, Ang II and PAI-1 antigen. Both imidapril and candesartan induced a similar SBP/DBP reduction (-19.4/16.8 and -19.5/16.3 mm Hg, respectively, P<0.001 vs. baseline). Both drugs decreased PAI-1 antigen after 4 weeks of treatment, but only the PAI-1 lowering effect of imidapril was sustained throughout the 16 weeks (-9.3 ng ml(-1), P<0.01 vs. baseline), whereas candesartan increased PAI-1 (+6.5 ng ml(-1), P<0.05 vs. baseline and P<0.01 vs. imidapril). Imidapril significantly decreased Ang II levels (-14.6 pg ml(-1) at week 16, P<0.05 vs. baseline), whereas candesartan increased them (+24.2 pg ml(-1), P<0.01 vs. baseline and vs. imidapril). In both groups there was a positive correlation between Ang II and PAI-1 changes (r=0.61, P<0.001 at week 16 for imidapril, and r=0.37, P<0.005 at week 16 for candesartan). Imidapril reduced plasma PAI-1 and Ang II levels, whereas candesartan increased them. This suggests that the different effect of angiotensin-converting enzyme inhibitors and Ang II blockers on Ang II production has a role in their different influence on fibrinolysis.
authors.affiliation: Department of Internal Medicine and Therapeutics, Centro Ipertensione e Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy. r.fogari@unipv.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Fogari
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zoppi
authors.forename: Amedeo
authors.initials: A
authors.lastname: Mugellini
authors.forename: Pamela
authors.initials: P
authors.lastname: Maffioli
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Lazzari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Derosa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D048289:Imidazolidines / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D013777:Tetrazoles / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D001786:Blood Glucose; D008076:Cholesterol, HDL; D048289:Imidazolidines; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D013777:Tetrazoles; D014280:Triglycerides; D000804:Angiotensin II; D002784:Cholesterol; C065166:imidapril; C081643:candesartan