Vascular effects of ACE inhibition independent of the renin-angiotensin system in hypertensive renovascular disease - A randomized, double-blind, crossover trial

To evaluate whether ACE inhibition and angiotensin II type 1 blockade exert beneficial effects on NO availability independent of their blood pressure- lowering effect, we used a double-blind crossover design to study vascular function in 18 patients with hypertensive renovascular disease during 6 wee ks of therapy with enalapril (Ena) and valsartan (Val) compared with non-re nin-angiotensin system-mediated treatment with the alpha (1)-blocker doxazo sin (Dox). Control measurements were performed in 13 age-matched volunteers . Forearm blood flow was assessed with venous occlusion plethysmography, an d serotonin and nitroprusside were used as endothelium-dependent and -indep endent vasodilators, respectively. Blood pressure was similar during all tr eatment periods. Serotonin-induced vasodilation was decreased in patients d uring Dox treatment (n=12) compared with control subjects (n=13) (increase 42+/-20% versus 107+/-65%, P<0.05). Crossover from Dox to Val (n=6) had no effect on serotonin response (increase 50+/-14%), but crossover to Ena (n=6 ) caused a significant improvement (increase 79+/-39%, P<0.05 versus Dox). In an assessment of all patients, serotonin-induced vasodilation during Ena (n=12, increase 75+/-31%) was increased compared with both Val and Dox (43 +/-14% and 42+/-20%, respectively; both P<0.05 versus Ena). The nitroprussi de response remained unaltered during all treatment periods. In conclusion, ACE inhibition improves the impaired endothelium-dependent vascular functi on in patients with hypertensive renovascular disease. This effect is unrel ated to blood pressure-lowering or angiotensin II-mediated effects.