title: Transient involvement of endothelin in hypertrophic remodeling of small arteries.
abstract: OBJECTIVE
  This study was designed to evaluate the capacity of norepinephrine (NE) to induce hypertrophic remodeling of small arteries in rats, and to determine the involvement of endothelin (ET) to initiate and maintain it.
  
  
  RESULTS
  Treatment with NE (2.5 microg/kg per min) for 14 or 28 days produced a similar inward hypertrophic remodeling, characterized by a smaller lumen, but increased media thickness and cross-sectional area. Arterial stiffness was reduced. Histological evaluation confirmed the hypertrophic nature of remodeling. Concomitant administration of LU135252 (ET-receptor antagonist) for the first 14 days of NE administration prevented the development of hypertrophy, without altering arterial mechanics. Treatment with the same antagonist from day 14 to day 28 of NE or angiotensin II (Ang II) treatment failed to regress established vascular hypertrophy. In contrast, normalization of arterial structure was observed with prazosin, an alpha-adrenergic blocker. Endothelin content in small mesenteric arteries showed a transient elevation following chronic NE administration.
  
  
  CONCLUSIONS
  Increased circulating NE levels are associated with hypertrophic remodeling of small arteries, in which ET plays an initiating role. However, the maintenance of vascular hypertrophy is ET-independent, either in the presence of augmented circulating levels of NE or Ang II. Thus, early rather than late treatment with ET-receptor antagonists may be a preferable approach to limit small artery-mediated end-organ damage in cardiovascular diseases.
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montréal, Québec, Canada.
authors.forename: H H
authors.initials: HH
authors.lastname: Dao
authors.forename: F M
authors.initials: FM
authors.lastname: Martens
authors.forename: R
authors.initials: R
authors.lastname: Larivière
authors.forename: N
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: P
authors.initials: P
authors.lastname: Cernacek
authors.forename: J
authors.initials: J
authors.lastname: de Champlain
authors.forename: P
authors.initials: P
authors.lastname: Moreau
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D016232:Endothelins / Q000502:physiology*; D006984:Hypertrophy; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D010666:Phenylpropionates / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014655:Vascular Resistance
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D010666:Phenylpropionates; D011743:Pyrimidines; D000804:Angiotensin II; C107831:darusentan; D009638:Norepinephrine