title: Functional remodelling of arterial endothelium during early postnatal development in rats.
abstract: OBJECTIVE
  Functional remodelling takes place permanently in the circulatory system. Whether this process also affects the anti-contractile effect of the endothelium during vasoconstrictor action is unknown. Therefore, the hypothesis was tested that the impact of the anti-contractile effect of the endothelium on agonist-induced contractions changes during early postnatal development.
  
  
  RESULTS
  We studied isometric contractions in saphenous arteries of young (1-2 weeks) and adult (2-3 months) rats. Real-time PCR and western blot were performed to evaluate the levels of mRNA expression and protein phosphorylation, respectively. In young but not in adult rats, methoxamine-induced contractions of endothelium-intact vessels exhibited a lower sensitivity compared with endothelium-denuded vessels. The endothelial influence on methoxamine-induced contractions in arteries of young rats was completely blocked by inhibition of endothelial NO-synthase (eNOS) and guanylate cyclase. NO-donor-induced vessel relaxations were not different in young and adult rats. The expression level of eNOS mRNA was prominently higher in arteries from young compared with adult rats. eNOS inhibition alone induced tonic contractions of endothelium-intact arteries from young but not from adult animals that were associated with corresponding changes in phosphorylation of the myosin regulatory light chains, the regulatory subunit of smooth muscle cell myosin light chain phosphatase, and vasodilator-stimulated phosphoprotein, the latter two being considered to be good markers of NO/sGC/PKG pathway activity.
  
  
  CONCLUSIONS
  We demonstrated that agonist-induced contractions in arteries of young rats are attenuated by the endothelium possessing an active NO-pathway. The active NO-pathway is due to a constitutive eNOS activity that disappears with age.
authors.affiliation: Cardiovascular Physiology, Centre for Biomedicine and Medical Technology Mannheim, Ruprecht-Karls-University Heidelberg, Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Gaynullina
authors.forename: Lubomir T
authors.initials: LT
authors.lastname: Lubomirov
authors.forename: Svetlana I
authors.initials: SI
authors.lastname: Sofronova
authors.forename: Vyacheslav U
authors.initials: VU
authors.lastname: Kalenchuk
authors.forename: Torsten
authors.initials: T
authors.lastname: Gloe
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pfitzer
authors.forename: Olga S
authors.initials: OS
authors.lastname: Tarasova
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schubert
mesh_terms: D000367:Age Factors; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D011150:Popliteal Artery / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001685:Biological Factors; D002867:Chromones; D009025:Morpholines; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D008729:Methoxamine
keywords: Endothelium; Functional remodelling; Nitric oxide; Protein phosphorylation; Saphenous artery