title: The upregulation of angiotensin-converting enzyme during neointima formation does not have functional consequences.
abstract: The aim of this study was to analyze if the upregulation of angiotensin-converting enzyme and AT1 receptors observed in a model of neointima formation results in increased contractions to angiotensin I (AI) and AII. Endothelial denudation was performed in left common carotid arteries of 3-month-old male Sprague-Dawley rats. Rats were killed at days 0, 4, 8 and 14 after injury and vascular reactivity was assessed in an organ bath. Responses were always compared with their contralateral vessels as a control. Contractile responses to 75 mM KCl were similar between groups. Noradrenaline (0.1 microM) induced significantly higher contractions at days 0 and 4. Relaxation to acetylcholine (Ach) (1 nM to 0.1 mM) was suppressed at day 0 and increased with time after injury. Relaxations to sodium nitroprusside (0.1 nM to 0.1 mM) were similar at all time points studied. Responses to AI and AII were increased at early steps of neointima formation and decreased with time after injury correlating with increased responses to Ach. Concentration-response curves to AI and AII had similar EC50 or Emax values at the same time points. These results indicate that in the rat i) neointima formation does not impair contractile responses to KCl nor relaxation to SNP, ii) a functional endothelium seems to regenerate with time after injury, and iii) the increase in ACE activity and AT1 receptor number does not have functional consequences.
authors.affiliation: Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: González
authors.forename: C
authors.initials: C
authors.lastname: Gómez
authors.forename: F
authors.initials: F
authors.lastname: Molero
authors.forename: M S
authors.initials: MS
authors.lastname: Fernández-Alfonso
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D017536:Carotid Artery, Common / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017539:Tunica Intima / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D015854:Up-Regulation
chemical_list: D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D009599:Nitroprusside; D011189:Potassium Chloride; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D000109:Acetylcholine; D009638:Norepinephrine