Angiotensin II type 1 receptor gene polymorphism is associated with an increased vascular reactivity in the human mammary artery in vitro.
A gene polymorphism of the angiotensin II (AII) type 1 receptor has been described previously (A to C transversion at position 1166). Besides the epidemiological studies needed to determine a possible relationship between the polymorphism and some cardiovascular diseases, no study has been conducted to determine the impact of the polymorphism on vascular functions. At subthreshold concentrations, within the physiological range, AII potentiates alpha-adrenergic-dependent vascular tone. We investigated phenylephrine-induced tone and its amplification by AII (10 pmol/l) in human internal mammary artery rings mounted in organ baths. We performed concentration-response curves to phenylephrine (0.1-100 micromol/l) before and after pretreatment with AII (10 pmol/l). Patients had the genotype AA (n = 20) or the A to C transversion (AC/CC, n = 30). Contractions to phenylephrine (0.1-100 micromol/l) were significantly higher in rings from AC/CC than from AA patients (maximum response: 1.47+/-0.07 vs. 1.22+/-0.06 mN/mg, p < 0.001). AII (10 pmol/l) induced a significant potentiation of phenylephrine-induced contraction (e.g. 58.9% increase in tone with 1 micromol/l phenylephrine, p < 0.001) which was significantly lower in the AC/CC than in the AA group (46+/-9 vs. 66+/-7% with 1 micromol/l phenylephrine, p < 0.01). Contractions to AII (1 or 100 nmol/l) were not significantly affected by the genotype. Although the study was performed in arteries from patients with a coronary artery disease, these changes in vascular reactivity might be of interest in the understanding of the relationship between a possible higher probability of cardiovascular disorder and the genetic polymorphism of the AII type 1 receptor.
Henrion
D
D
Institut National de la Santé et de la Recherche Médicale (INSERM) U 141, IFR Circulation-Lariboisière, Université Paris VII, Hôpital Lariboisière, Paris. daniel.henrion@inserm.1rb.ap-hop-paris.fr
Amant
C
C
Benessiano
J
J
Philip
I
I
Plantefève
G
G
Chatel
D
D
Hwas
U
U
Desmont
J M
JM
Durand
G
G
Amouyel
P
P
Lévy
B I
BI
D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D010656:Phenylephrine / Q000494:pharmacology; D017354:Point Mutation; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D010656:Phenylephrine