Effect of AT1 receptor blockade on endothelial function in essential hypertension

Klingbeil, A.U., John, S., Schneider, M.P., Jacobi, J., Handrock, R. and Schmieder, R.E. (2003) Effect of AT1 receptor blockade on endothelial function in essential hypertension. American Journal of Hypertension, 16(2), pp. 123-8. (doi: 10.1016/S0895-7061(02)03154-0)

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Abstract

Background: Angiotensin II adversely affects endothelial function and NO availability. We analyzed the effect of AT1 receptor blockade on endothelium-dependent vasodilation and basal nitric oxide (NO) production and release in hypertensive patients. <p></p> Methods and results: Sixty patients (53 ± 10 years) with essential hypertension were randomized to 6 weeks of double-blind therapy with either valsartan (80 mg), hydrochlorothiazide (HCTZ) (25 mg), or placebo once daily. Basal NO production and release was assessed by measuring forearm blood flow (FBF) in response to intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA), and endothelium-dependent vasodilation by measuring FBF in response to intra-arterial administration of acetylcholine, respectively. Intra-arterial infusion of noradrenaline and sodium nitroprusside was used to assess endothelium-independent changes in FBF. Blood pressure (BP) similarly decreased with active treatments (P < .001). After valsartan treatment, the decrease of FBF in response to L-NMMA was augmented (4 μmol/min L-NMMA, −1.3 ± 1.2 after v −0.5 ± 1.1 mL/min/100 mL before therapy, P < .02; 8 μmol/min L-NMMA: −1.7 ± 1.3 after v −1.1 ± 1.2 mL/min 100 mL before therapy, P < .05). No improvement was found after placebo or HCTZ treatment. Changes in L-NMMA-induced decrease of FBF with valsartan treatment were not related to BP changes. Neither drug substantially modified the response of FBF induced by intra-arterial infusion of acetylcholine, noradrenaline, and sodium nitroprusside. <p></p> Conclusions: The AT1 receptor blockade with valsartan improved basal NO production and release. The effect seems to be BP independent, as BP reduction with HCTZ failed to increase NO availability.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Schneider, Dr Markus
Authors: Klingbeil, A.U., John, S., Schneider, M.P., Jacobi, J., Handrock, R., and Schmieder, R.E.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:American Journal of Hypertension
ISSN:0895-7061

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