Angiotensin II Type 1 Receptor Antagonism Prevented the Effects of Hypercholesterolemia on Plasma Fibrinolytic Balance in Rabbits.
We have studied the effect of valsartan treatment (3 and 10 mg/kg/day) on plasma fibrinolytic balance in normo- and hypercholesterolemic rabbits. Animals were fed a normal chow or an experimental diet containing 1% cholesterol for 10 weeks. Systolic blood pressure, as well as plasma cholesterol, dimer D, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) were measured. Plasma cholesterol concentrations were higher in rabbits fed the experimental diet compared with control ones. None of the doses of valsartan were able to affect either plasma cholesterol or blood pressure levels in any group.As compared with control animals hypercholesterolemic rabbits presented lower dimer D (0.37±0.07 mg/ml vs 0.96±0.13, p<0.05) and tPA levels (0.27±0.003 ng/ml vs 0.31±0.007, p<0.05) but higher PAI-1 levels (11.1±0.9 ng/ml vs 8.84±0.04, p<0.05). In cholesterol-fed rabbits, valsartan treatment (3 or 10 mg/kg/day) significantly increased both dimer D (0.73±0.1 mg/ml and, 1.3±0.2, respectively, p<0.05) and tPA (0.29±0.007 ng/ml and 0.3±0.01, respectively, p<0.05) levels. Likewise, both doses of valsartan reduced PAI-1 concentrations (9.4±0.1 ng/ml and 9.2±=.1, respectively, p<0.05). By contrast, valsartan treatment was unable to modify these parameters in control rabbits. All these data suggest that, in rabbits, hypercholesterolemia is associated with an impaired plasma fibrinolytic balance. In addition, prolonged treatment with valsartan prevented all these changes without modifying either plasma cholesterol or bllod pressure levels.This supports that angiotensin II may play a role in the thrombotic complications of athrosclerosis.