The angiotensin II receptor type 2 polymorphism influences haemodynamic function and circulating RAS mediators in normotensive humans.
BACKGROUND
The haemodynamic responses to angiotensin II type 1 (AT1) receptor blockade may be mediated in part by interactions between angiotensin II and the angiotensin II type 2 receptor (AT2R). An AT2R G1675A gene polymorphism has been described, but the functional effects of this polymorphism are unknown.


METHODS
Haemodynamic function, circulating renin-angiotensin system mediators and norepinephrine were measured in young healthy subjects at baseline and at 2 and 4 weeks after treatment with irbesartan. Subjects were divided into two groups on the basis of the AT2R G1675A gene polymorphism: GG subjects (n = 12) and AA/GA subjects (n = 22).


RESULTS
AA/AG subjects exhibited hypotensive and renal vasodilatory responses to irbesartan at 4 weeks, but GG subjects did not. In accord with haemodynamic effects, circulating aldosterone levels were suppressed in AA/AG, while circulating norepinephrine levels were augmented only in GG subjects. In contrast, increases in circulating renin, angiotensin II and plasma renin activity after irbesartan were exaggerated in AA/AG subjects.


CONCLUSIONS
The AT2R G1675A polymorphism is a determinant of haemodynamic responses to AT1 receptor blockade, an effect that may be due to influences on aldosterone escape.
Cherney
David Z I
DZ
Division of Nephrology, Toronto General Hospital, University of Toronto ON, Canada. david.cherney@uhn.on.ca
Lai
Vesta
V
Miller
Judith A
JA
Scholey
James W
JW
Reich
Heather N
HN
D000328:Adult; D000804:Angiotensin II / Q000097:blood*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000077405:Irbesartan; D007668:Kidney / Q000098:blood supply; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000235:genetics*; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; D012083:Renin; D000077405:Irbesartan