Arterial stiffness and angiotensinogen gene in hypertensive patients and mutant mice.
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.
Bozec
Erwan
E
Department of Pharmacology, Hôpital Européen Georges Pompidou and Institut National de la Santé et de la Recherche Médicale EMI 0107, Paris, France.
Lacolley
Patrick
P
Bergaya
Sonia
S
Boutouyrie
Pierre
P
Meneton
Pierre
P
Herissé-Legrand
Monique
M
Boulanger
Chantal M
CM
Alhenc-Gelas
François
F
Kim
Hyung-Suk
HS
Laurent
Stéphane
S
Dabiré
Hubert
H
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
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen