Differential effects of ACE-inhibition and angiotensin II antagonism on fibrinolysis and insulin sensitivity in hypertensive postmenopausal women.
The aim of this study was to compare the effects of trandolapril and losartan on plasminogen activator inhibitor type 1 (PAI-1) levels and insulin sensitivity in hypertensive postmenopausal women. We studied 89 hypertensive (diastolic blood pressure >90 and <110 mm Hg) postmenopausal women, aged 51 to 60 years not taking any hormone replacement therapy. Diabetic, obese, and smoking patients were excluded. After a 4-week placebo period, they were randomized to receive 2 mg of oral trandolapril (n=45) or 50 mg of oral losartan (n=44) for 12 weeks according to a double-blind, parallel group design. At the end of the placebo and active treatment periods, blood pressure (BP) was measured, plasma samples were drawn to evaluate PAI-1 antigen levels, and insulin sensitivity was assessed. Both trandolapril and losartan reduced systolic BP (by a mean of 16.9 mm Hg and 15.2 mm Hg, respectively, P < .01 v placebo) and diastolic BP (by a mean of 13.1 mm Hg and 11.9 mm Hg, respectively, P < .01 v placebo) with no difference between the two treatments. The PAI-1 antigen levels were significantly decreased by trandolapril (from 36.9+/-21 ng/dL to 27.2+/-17 ng/dL, P < .05), but not by losartan (from 35.3+/-22 ng/dL to 37.1+/-23 ng/dL, P=not significant). Glucose infusion rate was significantly increased by trandolapril (from 6.67+/-0.56 mg/min/kg to 7.9+/-0.65 mg/min/kg, P < .05), but was not significantly modified by losartan (from 6.7+/-0.47 mg/min/kg to 6.9+/-0.50 mg/min/kg, P= not significant). In the trandolapril group the PAI-1 decrease correlated with glucose infusion rate increase (r=0.36, P=.045) These results provide evidence of different effects of angiotensin converting enzyme inhibitors and AT1 antagonists on fibrinolysis and suggest that the PAI-1 decrease induced by angiotensin converting enzyme inhibitors is related to their action on insulin sensitivity and is not dependent on angiotensin II antagonism but rather on other mechanisms. It remains to be seen whether these findings apply to other patient populations than postmenopausal women.
Fogari
R
R
Department of Internal Medicine and Therapeutics, University of Pavia, Clinica Medica I, IRCCS, Policlinico S. Matteo, Italy.
Zoppi
A
A
Preti
P
P
Fogari
E
E
Malamani
G
G
Mugellini
A
A
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D019808:Losartan / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017698:Postmenopause / Q000097:blood* / Q000187:drug effects*; D012680:Sensitivity and Specificity; D016387:Women's Health
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001786:Blood Glucose; D007211:Indoles; D007328:Insulin; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; D000804:Angiotensin II; C052035:trandolapril; D019808:Losartan