title: Fibrinolysis and insulin sensitivity in imidapril and candesartan (FISIC study) recipients with hypertension.
abstract: The aim of this study was to evaluate the effects of imidapril and candesartan on fibrinolysis and insulin sensitivity in normoweight hypertensive patients. After a 2-week wash-out period, 61 patients with mild-to-moderate hypertension were randomized to imidapril or candesartan for 12 weeks. Blood pressure (BP), plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen activities were evaluated at baseline and during treatment. The patients underwent a euglycemic-hyperinsulinemic clamp (insulin sensitivity was evaluated as glucose infusion rate during the last 30 min) and a desmopressin test (with desmopressin infusion in the brachial artery) to evaluate endothelial ability to release t-PA. Imidapril and candesartan induced similar systolic/diastolic BP reductions (-16/12.6 and -16.1/12.2 mm Hg, respectively, P<0.001 vs. baseline). Imidapril increased glucose infusion rate (+1.1 mg min(-1) per kg, P<0.02), whereas candesartan did not change it. Both drugs decreased PAI-1 antigen activity after 4 weeks of treatment; subsequently, only the decreasing effect of imidapril was sustained throughout the 12 weeks, whereas candesartan increased PAI-1 activity at week 12 (P<0.05 vs. baseline, P<0.01 vs. imidapril). Activity of t-PA decreased with candesartan (from 0.48±0.16 to 0.43±0.14 IU ml(-1), P<0.05) but not with imidapril. Activity of t-PA in response to desmopressin was increased more by imidapril (+4.45 IU ml(-1)) than by candesartan (+2.73 IU ml(-1), P<0.01 vs. imidapril). These results indicate that in normoweight hypertensive patients, despite similar BP reduction, imidapril but not candesartan improved the fibrinolytic balance, suggesting that mechanisms other than Ang II inhibition, possibly including bradykinin-mediated effects on insulin sensitivity and endothelial function, may be responsible for these different effects.
authors.affiliation: Department of Internal Medicine and Therapeutics, Clinica Medica II, 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: Sibilla A T
authors.initials: SA
authors.lastname: Salvadeo
authors.forename: Amedeo
authors.initials: A
authors.lastname: Mugellini
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Lazzari
authors.forename: Tara
authors.initials: T
authors.lastname: Santoro
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 / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D048289:Imidazolidines / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D015398:Signal Transduction / Q000502:physiology; D016037:Single-Blind Method; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000097:blood; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D048289:Imidazolidines; D017395:Plasminogen Activator Inhibitor 1; D013777:Tetrazoles; D000804:Angiotensin II; C065166:imidapril; D010959:Tissue Plasminogen Activator; C081643:candesartan