AT2 receptors in cardiovascular and renal diseases

Abstract

The renin-angiotensin system (RAS) plays an important role in the initiation and progression of cardiovascular and renal diseases. These actions mediated by AT1 receptor (AT1R) are well established and led to development of selective AT1R blockers (ARBs). In contrast, there is scientific evidence that AT2 receptor (AT2R) mediates effects different from and often opposing those of the AT1R. Meagrely expressed in healthy tissue the AT2R is upregulated in injuries providing an endogenous protection to inflammatory, oxidative and apoptotic processes. Interestingly the beneficial effects mediated by AT2R can be further enhanced by pharmacological intervention using the recently developed AT2R agonists. This review article summarizes our current knowledge about regulation, signalling and effects mediated by AT2R in health and disease, with emphasis on cardiac and renal systems. At the end a novel concept of natural protective systems will be introduced and discussed as an attractive target in drug development.

Angiotensin receptor signaling in sickle cell anemia has a reno‐protective effect on urine concentrating ability but results in sickle glomerulopathy

“…In a diabetic rat model, C21 treatment has been shown to be effective in reducing tubulointerstitial fibrosis. 4 Our data of improved UCA in SCA with C21 highlights another important reno-protective role of increased AT 2 R signaling. Taken together, our data shows that in SCA, AT signaling via both AT 1 R and AT 2 R compensates for the sickling-mediated loss of UCA..…”

“…4 However, we found that AT signaling via AT 2 R did not cause sickle glomerulopathy since SS/AT 2 R-deficient mice developed albuminuria and FSGS similar to SS/WT chimeras (Fig. 1d, Supplemental Fig.…”

“…AT 2 R stimulation causes natriuresis and blood pressure regulation, and its deficiency is associated with severe experimentally-induced acute tubular necrosis. 4 We hypothesized that increased AT 2 R signaling probably compensates for loss of UCA with losartan, which may explain the captopril effect.…”

Vasoprotective Effect of Physalis Angulata L. Leaf Water Extract on Kidney of Nω-Nitro-L-Arginine Methyl Ester-Induced Endothelial Dysfunction Rat Model

“…AT2-receptor stimulation can increase NO levels [45], possibly through direct stimulation of NOS and bradykinin pathway [46]. The AT2-receptor stimulation reduces inflammatory response through JAK/STAT inhibition, NF-κB inhibition, and COX2 synthesis inhibition [47]. Therefore, in this study, we assumed that the reduction of NO levels induced by L-NAME still can be compensated by AT2 stimulation to AT2-receptor.…”

Renin-Angiotensin-Aldosterone System in Heart Failure: Focus on Nonclassical Angiotensin Pathways as Novel Upstream Targets Regulating Aldosterone

“…Indeed, overactivation of AT 1 R contributes to the pathophysiology of heart failure inducing cardiac fibrosis, inflammation, cell proliferation, coronary vasoconstriction, and cardiomyocyte hypertrophy, as well as apoptosis [25], cardiac remodeling [25,26], vascular stiffness and atherosclerosis [27], endothelial dysfunction, oxidative stress, or insulin resistance [28]. Ang II may also stimulate AT 2 R that has a vasoprotective profile-anti-inflammatory, antifibrotic, and anti-apoptotic-involving the activation of bradykinin/NO/cGMP system [29]. AT 2 R is linked also to the regulation of vascular and cardiac growth responses [30].…”