title: Vascular Effects of ACE Inhibition Independent of the Renin-Angiotensin System in Hypertensive Renovascular Disease : A Randomized, Double-Blind, Crossover Trial.
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 alpha(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.
authors.affiliation: Department of Nephrology and Hypertension (J.M.A. van A., J.J.B., H.A.K.), University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Jacobine M. A.
authors.initials: JM
authors.lastname: van Ampting
authors.forename: Michel L.
authors.initials: ML
authors.lastname: Hijmering
authors.forename: Jaap J.
authors.initials: JJ
authors.lastname: Beutler
authors.forename: Ronald E.
authors.initials: RE
authors.lastname: van Etten
authors.forename: Hein A.
authors.initials: HA
authors.lastname: Koomans
authors.forename: Ton J.
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: Erik S. G.
authors.initials: ES
authors.lastname: Stroes