AT2 receptors: Functional relevance in cardiovascular disease

Abstract

The renin angiotensin system (RAS) is intricately involved in normal cardiovascular homeostasis. Excessive stimulation by the octapeptide angiotensin II contributes to a range of cardiovascular pathologies and diseases via angiotensin type 1 receptor (AT1R) activation. On the other hand, tElsevier Inc.he angiotensin type 2 receptor (AT2R) is thought to counter-regulate AT1R function. In this review, we describe the enhanced expression and function of AT2R in various cardiovascular disease settings. In addition, we illustrate that the RAS consists of a family of angiotensin peptides that exert cardiovascular effects that are often distinct from those of Ang II. During cardiovascular disease, there is likely to be an increased functional importance of AT2R, stimulated by Ang II, or even shorter angiotensin peptide fragments, to limit AT1R-mediated overactivity and cardiovascular pathologies.

Both AT1and AT2receptors mediate proliferation and migration of porcine vascular smooth muscle cells

“…Distinct contributions by both AT 1 and AT 2 receptor subtypes have been demonstrated in hypertensive rats that exhibited AT 1 -mediated changes in blood pressure but AT 2 -mediated SMC hypertrophy (9). Similar observations have been made in normotensive Sprague-Dawley rats, leading to speculation that the activation of both AT 1 and AT 2 receptors is necessary for the trophic and proliferative effects of ANG II (2).…”

“…As a consequence, many studies of SMCs have not included an analysis of the AT 2 receptor and fewer details of its biological functions have thus been elucidated (25). Although adult aorta express a small but significant population of AT 2 receptors (5), AT 2 receptor expression is also influenced by cardiovascular disease states such as diabetes (1), hypertension (25), and heart failure (9).…”

Aliskiren Reduces Myocardial Ischemia–Reperfusion Injury by a Bradykinin B 2 Receptor– and Angiotensin AT 2 Receptor–Mediated Mechanism

“…Other mechanisms that contribute to the therapeutic effects of ACE inhibitors and ARBs include increased bradykinin, angiotensin II, and angiotensin-(1-7) levels and increased activation of B 2 , AT 2 , and Mas receptors. [46][47][48][49] However, when given in combination with ACE inhibitors and ARBs, the renin inhibitor aliskiren may attenuate angiotensin II and angiotensin-(1-7) levels and thus Valsartan blocks the AT 1 receptor, PD123319 blocks the AT 2 receptor, and icatibant blocks the B 2 receptor. By blocking the tonic Ang II-mediated inhibition of renin secretion, valsartan increases renin, Ang I, and Ang II levels.…”

Stimulation of angiotensin AT2 receptors by the non‐peptide agonist, Compound 21, evokes vasodepressor effects in conscious spontaneously hypertensive rats

“…This in vitro effect was not dependent on background AT1 receptor blockade, as it was in vivo, and was also inhibited by L-NAME. Thus, Compound 21 elicited classical AT2 receptor-mediated NO signalling, a hallmark of AT 2 receptors in vascular tissue (Widdop et al, 2003;Jones et al, 2008). This compound was also tested using rat isolated mesenteric arteries, a preparation well recognized as exhibiting AT2 receptor-mediated vasorelaxation (Matrougui et al, 1999;Henrion et al, 2001;Widdop et al, 2002).…”

“…The octapeptide angiotensin II (Ang II) is the main biologically active mediator of the renin-angiotensin system and plays an important role in cardiovascular function by influencing vascular tone, structure, fluid and electrolyte balance via direct effects on endothelial and smooth muscle cells (Widdop et al, 2003;Jones et al, 2008). Two main receptor subtypes have been identified as binding sites for Ang II: angiotensin type 1 receptor (AT1 recepter) and type 2 receptor (AT2 receptor) (de Gasparo et al, 2000); nomenclature follows Alexander et al, 2008).…”