Dimerization of AT2 and Mas Receptors in Control of Blood Pressure

Curr Hypertens Rep. 2018 May 1;20(5):41. doi: 10.1007/s11906-018-0845-3.

Abstract

Purpose of review: Angiotensin type 2 receptor (AT2R) and receptor Mas (MasR) are part of the "protective arm" of the renin angiotensin system. Gene and pharmacological manipulation studies reveal that AT2R and MasR are involved in natriuretic, vasodilatory, and anti-inflammatory responses and in lowering blood pressure in various animal models under normal and pathological conditions such as salt-sensitive hypertension, obesity, and diabetes. The scope of this review is to discuss co-localization and heterodimerization as potential molecular mechanisms of AT2R- and MasR-mediated functions including antihypertensive activities.

Recent findings: Accumulating evidences show that AT2R and MasR are co-localized, make a heterodimer, and are functionally interdependent in producing their physiological responses. Moreover, ang-(1-7) preferably may be an AT1R-biased agonist while acting as a MasR agonist. The physical interactions of AT2R and MasR appear to be an important mechanism by which these receptors are involved in blood pressure regulation and antihypertensive activity. Whether heteromers of these receptors influence affinity or efficacy of endogenous or synthetic agonists remains a question to be considered.

Keywords: Angiotensin II type 1 receptor; Angiotensin II type 2 receptor; Blood pressure; Dimerization; Functional interdependence; Mas receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Blood Pressure / physiology*
  • Dimerization
  • Humans
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 1 / physiology
  • Receptor, Angiotensin, Type 2 / metabolism*
  • Receptor, Angiotensin, Type 2 / physiology
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, G-Protein-Coupled / physiology
  • Renin-Angiotensin System / physiology*

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, G-Protein-Coupled