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(Hypertension. 2001;37:40.)
© 2001 American Heart Association, Inc.

Scientific Contributions

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

A Randomized, Double-Blind, Crossover Trial

Jacobine M. A. van Ampting; Michel L. Hijmering; Jaap J. Beutler; Ronald E. van Etten; Hein A. Koomans; Ton J. Rabelink; Erik S. G. Stroes

From the Department of Nephrology and Hypertension (J.M.A. van A., J.J.B., H.A.K.), University Medical Center Utrecht, Utrecht, the Netherlands; and Department of Vascular Medicine (J.M.A. van A., M.L.H., R.E. van E., T.J.R., E.S.G.S.), University Medical Center Utrecht, Utrecht, the Netherlands.

Correspondence to Dr E.S.G. Stroes, Department of Vascular Medicine, F03.226, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. E-mail E.Stroes{at}digd.azu.nl

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 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.

Key Words: endothelium • angiotensin-converting enzyme inhibitors • angiotensin • receptors, angiotensin • nitric oxide • hypertension, renovascular