title: Effect of AT1 receptor blockade on endothelial function in essential hypertension.
abstract: BACKGROUND
  Angiotensin II adversely affects endothelial function and NO availability. We analyzed the effect of AT(1) receptor blockade on endothelium-dependent vasodilation and basal nitric oxide (NO) production and release in hypertensive patients.
  
  
  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 N(G)-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 micromol/min L-NMMA, -1.3 +/- 1.2 after v -0.5 +/- 1.1 mL/min/100 mL before therapy, P < .02; 8 micromol/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.
  
  
  CONCLUSIONS
  The AT(1) 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.
authors.affiliation: Department of Medicine IV, University of Erlangen-Nümberg, Erlangen-Nürnberg, Germany.
authors.forename: Arnfried U
authors.initials: AU
authors.lastname: Klingbeil
authors.forename: Stefan
authors.initials: S
authors.lastname: John
authors.forename: Markus P
authors.initials: MP
authors.lastname: Schneider
authors.forename: Johannes
authors.initials: J
authors.lastname: Jacobi
authors.forename: Renate
authors.initials: R
authors.lastname: Handrock
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
mesh_terms: D000109:Acetylcholine; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D015331:Cohort Studies; D004232:Diuretics; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D004791:Enzyme Inhibitors; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1; D012039:Regional Blood Flow / Q000187:drug effects; D012146:Rest; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000068756:Valsartan; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D004232:Diuretics; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D049993:Sodium Chloride Symporter Inhibitors; D013777:Tetrazoles; D014665:Vasodilator Agents; D006852:Hydrochlorothiazide; D019323:omega-N-Methylarginine; D000068756:Valsartan; D014633:Valine; D000109:Acetylcholine