Regulator of
G-protein signaling 2 (RGS2) negatively regulates the signaling of
G-protein-coupled receptors, such as the
angiotensin II (AngII) type 1 receptor by accelerating the inactivation of Gαq. Rgs2-deficient mice show increased sensitivity and prolonged responsiveness to
vasoconstrictors, and genetic variations in the RGS2 gene are associated with
hypertension in humans. This study aimed to clarify whether Rgs2 deficiency contributes to the development of
vascular remodeling and therapeutic efficacy of the
angiotensin receptor blocker telmisartan on atherosclerotic vascular damage. We treated Rgs2(+/+), Rgs2(+/-) and Rgs2(-/-) mice with saline (control group), AngII (1000 ng per kg per min, AngII group) or low-dose
telmisartan (0.3 mg per kg per day) with AngII infusion (AngII+Telmi group) for 4 weeks. For all genotypes, the AngII groups exhibited significantly higher blood pressure, a higher mortality rate and a higher incidence of
aortic aneurysm than the respective control group. Interestingly,
aneurysm incidence was decreased in the AngII+Telmi group compared with the AngII group in Rgs2(-/-) mice (6.7 vs. 42.9%, P<0.05), but not in Rgs2(+/+) mice (38.9 vs. 40.0%). Moreover, in Rgs2(-/-) mice, the AngII+Telmi group exhibited significant improvement in survival, reduction of enlarged aortic diameter, inhibition of
superoxide production and suppression of
NAD(P)H oxidase activity compared with the AngII group. Thus, Rgs2 deficiency potentiates the vascular protection effect of low-dose
telmisartan. Our results suggest that
angiotensin receptor blocker may be useful for protection from cardiovascular events in hypertensive subjects with risk alleles in the RGS2 gene.