Distinct and combined vascular effects of ACE blockade and HMG-CoA reductase inhibition in hypertensive subjects

Hypercholesterolemia and hypertension are frequently associated with elevat ed sympathetic activity. Both are independent cardiovascular risk factors a nd both affect endothelium-mediated vasodilation. To identify the effects o f cholesterol-lowering and antihypertensive treatments on vascular reactivi ty and vasodilative capacity, we studied 30 hypercholesterolemic hypertensi ve subjects. They received placebo for 4 weeks, either enalapril or simvast atin for 14 weeks, and, finally, both medications for an additional 14 week s. Postischemic forearm blood flow (MFBF) and minimal vascular resistance ( mFVR) were used as indices of vasodilative capacity and structural vascular damage, respectively. Total (resting-stress-recovery phases) cardiovascula r (blood pressure [BP] and heart rate [HR]) and regional hemodynamic (FBF a nd FVR) reactivity to stressful stimuli were calculated as area-under-the-c urve (auc) (value X time). Compared with baseline levels, simvastatin reduc ed total (TOT-C) and LDL cholesterol (LDL-C) (1.27 mmol/L, P<0.001 and 1.33 mmol/L, P < 0.001, respectively). Enalapril also reduced TOT-C and LDL-C ( 0.6 mmol/L, P<0.001 and 0.58 mmol/L, P<0.05, respectively). MFBF was increa sed substantially by both treatments (P<0.001). Enalapril had a greater eff ect (-1.7 arbitrary units (AU), P<0.001) than simvastatin (-0.6 AU, P<0.05) on mFVR. During stress, FBF increased more with enalapril (4.4 FBF X minut es, P<0.001) than with simvastatin (1.8 FBF X minutes, P<0.01). Conversely, FVR stress response was reduced more with enalapril (9.1 FVR X minutes, P< 0.001) than with simvastatin (2.9 FVR X minutes, P<0.01). During combinatio n treatment, a significant (0.001 > P<0.05) additive effect on hypercholest erolemia, structural vascular damage, BP, and FVR was shown. The findings s uggest that angiotensin-converting enzyme (ACE) inhibition induces a larger reduction than HMG-CoA reductase blockade in vascular reactivity and struc tural damage in hypercholesterolemic hypertensive subjects.