title: Chronic reduction of nitric oxide level in adult spontaneously hypertensive rats induces aortic stiffness similar to old spontaneously hypertensive rats.
abstract: BACKGROUND
  Age and hypertension are two major determinants of arterial stiffness, as well as endothelial dysfunction. The present study was designed to test whether a chronic reduction of endogenous nitric oxide (NO) produces arterial stiffening close to that observed in old spontaneously hypertensive rats (SHR), and also to study the effect of an acute or a chronic decrease in blood pressure (BP) on aortic distensibility.
  
  
  METHODS
  BP, aortic stiffness, endothelial dysfunction and remodelling were measured in male adult (20-week-old) SHR, in adult SHR treated with a nonspecific NO synthase inhibitor L-NAME (SHR/L-NAME) for 2 weeks, in adult SHR/L-NAME cotreated with perindopril (1 mg/kg/day) and in old SHR (55-week-old). Age-matched WKY were used as a normotensive group.
  
  
  RESULTS
  Aortic endothelial dysfunction, remodelling and stiffening appeared in old SHR. Reduction of NO production in adult SHR caused similar alterations. Acute decreases in BP in SHR/L-NAME did not improve isobaric aortic distensibility but a chronic reduction of BP prevented endothelial dysfunction, aortic remodelling and aortic wall stiffening.
  
  
  CONCLUSIONS
  NO reduction in adult SHR induces aortic alterations similar to those observed during aging, which supports the major role of NO in the development of arterial stiffening. These aortic alterations can be prevented by angiotensin-converting enzyme inhibitor treatment.
authors.affiliation: Institut de Recherches Servier (IdRS), Suresnes, France. marc.isabelle@fr.netgrs.com
authors.forename: Marc
authors.initials: M
authors.lastname: Isabelle
authors.forename: Serge
authors.initials: S
authors.lastname: Simonet
authors.forename: Christophe
authors.initials: C
authors.lastname: Ragonnet
authors.forename: Patricia
authors.initials: P
authors.lastname: Sansilvestri-Morel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Clavreul
authors.forename: Christine
authors.initials: C
authors.lastname: Vayssettes-Courchay
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Verbeuren
mesh_terms: D000375:Aging / Q000473:pathology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D020913:Perindopril / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester; D020913:Perindopril