title: Arterial stiffness and angiotensinogen gene in hypertensive patients and mutant mice.
abstract: OBJECTIVE
  To determine whether carotid artery stiffness was increased in patients with untreated essential hypertension who are homozygous for the T allele of the M235T polymorphism of the angiotensinogen (AGT) gene and in mutant mice carrying three copies of the angiotensinogen (Agt) gene.
  
  
  METHODS
  Using echotracking systems, we studied carotid mechanical properties in 98 never-treated hypertensive patients according to their AGT genotype, and in Agt mutant mice.
  
  
  RESULTS
  Patients homozygous for the T allele had a reduced carotid distensibility and an increased stiffness of the carotid wall material (Young's elastic modulus), independent of blood pressure, compared with patients homozygous for the M allele. In Agt1/2 mice, carotid distensibility was not significantly different from that of Agt1/1 (wild-type). Moreover, the stiffness of the arterial wall material was lower in Agt1/2 mice than in wild-type mice. In Agt1/2 mice, the greater blood pressure was not associated with arterial hypertrophy, resulting in a greater circumferential wall stress. The in-vivo and in-vitro pressor responses to angiotensin II were reduced in Agt1/2 mice, whereas the contractile response to phenylephrine was not significantly different between Agt1/1 and Agt1/2 mice, indicating the integrity of the contractile apparatus and suggesting a dysfunction of the angiotensin II type 1 receptor signalling pathways in Agt1/2 mice.
  
  
  CONCLUSIONS
  These data suggest that the angiotensinogen TT genotype at position 235 could be a genetic marker for arterial stiffness in patients with never-treated hypertension, whereas in Agt1/2 mice the dysfunction of the angiotensin II type 1 receptor signalling pathways could explain the lack of arterial wall hypertrophy and stiffness.
authors.affiliation: Department of Pharmacology, Hôpital Européen Georges Pompidou and Institut National de la Santé et de la Recherche Médicale EMI 0107, Paris, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bozec
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacolley
authors.forename: Sonia
authors.initials: S
authors.lastname: Bergaya
authors.forename: Pierre
authors.initials: P
authors.lastname: Boutouyrie
authors.forename: Pierre
authors.initials: P
authors.lastname: Meneton
authors.forename: Monique
authors.initials: M
authors.lastname: Herissé-Legrand
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Boulanger
authors.forename: François
authors.initials: F
authors.lastname: Alhenc-Gelas
authors.forename: Hyung-Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Stéphane
authors.initials: S
authors.lastname: Laurent
authors.forename: Hubert
authors.initials: H
authors.lastname: Dabiré
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen