The angiotensin AT2 receptor in left ventricular hypertrophy.
Left ventricular hypertrophy (LVH) is considered a major predictor of cardiovascular morbidity and mortality. While it is unanimously accepted that the angiotensin AT1 receptor is involved in the pathogenesis of hypertension and LVH, the role of the AT2 receptor in LVH is still controversial. Most studies addressing the involvement of the AT2 receptor in LVH have been performed in genetically altered, either AT2 receptor-deficient or AT2 receptor-overexpressing mice. Unfortunately, this experimental approach turned out to yield highly controversial results with an almost equal number of studies supporting prohypertrophic or antihypertrophic or neutral effects of the AT2 receptor in LVH. Interestingly, in-vivo studies in wild-type animals using the AT2 receptor antagonist, PD123319, are less controversial and mainly revealed antigrowth effects of the AT2 receptor provided the study duration was sufficiently long. In the future, the novel non-peptide AT2 receptor agonist, compound 21, will allow the effects of the AT2 receptor in LVH to be studied by direct, selective AT2 receptor stimulation in vivo- a novel approach, which will hopefully help to overcome current controversies.
Steckelings
U Muscha
UM
Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, Hessische Strasse 3-4, Berlin, Germany. ulrike.steckelings@charite.de
Widdop
Robert E
RE
Paulis
Ludovit
L
Unger
Thomas
T
D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D011725:Pyridines / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000502:physiology*
D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; C073402:PD 123319