Vascular Effects of ACE Inhibition Independent of the Renin-Angiotensin System in Hypertensive Renovascular Disease

Abstract

Abstract —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 weeks of therapy with enalapril (Ena) and valsartan (Val) compared with non–renin-angiotensin system–mediated treatment with the α 1 -blocker doxazosin (Dox). Control measurements were performed in 13 age-matched volunteers. Forearm blood flow was assessed with venous occlusion plethysmography, and serotonin and nitroprusside were used as endothelium-dependent and -independent vasodilators, respectively. Blood pressure was similar during all treatment periods. Serotonin-induced vasodilation was decreased in patients during 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 nitroprusside response remained unaltered during all treatment periods. In conclusion, ACE inhibition improves the impaired endothelium-dependent vascular function in patients with hypertensive renovascular disease. This effect is unrelated to blood pressure–lowering or angiotensin II–mediated effects.