title: Effect of aliskiren treatment on endothelium-dependent vasodilation and aortic stiffness in essential hypertensive patients.
abstract: OBJECTIVE
  Aliskiren is a new oral non-peptide renin inhibitor. Its effects on vascular function in human hypertension are unknown. We assessed whether aliskiren may improve peripheral endothelial function and arterial stiffness in essential hypertensive patients (EH), when compared with the angiotensin-converting enzyme-inhibitor ramipril.
  
  
  RESULTS
  Fifty EH received treatment with aliskiren (150-300 mg/daily) or ramipril (5-10 mg/daily) for 12 weeks, according to a randomized, open with blind endpoints, parallel group design. We studied the forearm blood flow (straingauge plethysmography) response to intrabrachial acetylcholine, repeated under the nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA) (4 μmol/min), or the antioxidant ascorbic acid (8 mg/100 mL/min). Carotid-to-femoral pulse wave velocity (PWV), central blood pressure and augmentation index (AIx) were obtained by applanation tonometry. Brachial blood pressure was similarly normalized by aliskiren (from 149/94 to 136/86 mmHg) and ramipril (from 148/92 to 135/85 mmHg), as well as central blood pressure. Aliskiren increased (P < 0.001) the vasodilation to acetylcholine and restored the inhibitory effect of l-NMMA on acetylcholine. Ascorbic acid, which at baseline potentiated the response to acetylcholine, no longer improved endothelium-dependent relaxation after aliskiren treatment. In contrast, ramipril failed to affect the response to acetylcholine, the lacking inhibitory effect of l-NMMA, or the potentiating effect of ascorbic acid. Pulse wave velocity was significantly (P < 0.05) and similarly reduced by both drugs. Aliskiren induced a significantly (P < 0.05) greater AIx reduction than ramipril.
  
  
  CONCLUSIONS
  Aliskiren increased nitric oxide availability in the forearm resistance arterioles of EH, an effect probably determined by an antioxidant activity, which can also contribute to improved peripheral wave reflection.
authors.affiliation: Department of Internal Medicine, University of Pisa, Pisa, Italy. agostino.virdis@med.unipi.it
authors.forename: Agostino
authors.initials: A
authors.lastname: Virdis
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: Ahmad Amedeo
authors.initials: AA
authors.lastname: Qasem
authors.forename: Gianni
authors.initials: G
authors.lastname: Lorenzini
authors.forename: Emiliano
authors.initials: E
authors.lastname: Duranti
authors.forename: Giulia
authors.initials: G
authors.lastname: Cartoni
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Bruno
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bernini
authors.forename: Stefano
authors.initials: S
authors.lastname: Taddei
mesh_terms: D000328:Adult; D000577:Amides / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001160:Arterioles / Q000187:drug effects; D001783:Blood Flow Velocity / Q000502:physiology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D005650:Fumarates / Q000008:administration & dosage*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000008:administration & dosage*; D014655:Vascular Resistance / Q000502:physiology; D059289:Vascular Stiffness / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D005650:Fumarates; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; C446481:aliskiren; D017257:Ramipril