Renal effects of angiotensin II in the newborn period: role of type 1 and type 2 receptors

Abstract

BackgroundEvidence suggests a critical role for the renin-angiotensin system in regulating renal function during postnatal development. However, the physiological relevance of a highly elevated renin-angiotensin system early in life is not well understood, nor which angiotensin receptors might be involved. This study was designed to investigate the roles of angiotensin receptors type 1 (AT1R) and type 2 (AT2R) in regulating glomerular and tubular function during postnatal development.MethodsThe renal effects of the selective antagonist to AT1R, ZD 7155 and to AT2R, PD 1233319 were evaluated in two groups of conscious chronically instrumented lambs aged ~ one week (N = 8) and ~ six weeks (N = 10). Two experiments were carried out in each animal and consisted of the assessment of renal variables including glomerular and tubular function, for 30 min before (Control) and 60 min after infusion of ZD 7155 and PD 123319, respectively. Statistical significance was determined using parametric testing (Student t-test, analysis of variance ANOVA) as appropriate.ResultsZD 7155 infusion was associated with a significant decrease in glomerular filtration rate and filtration fraction at one but not six weeks; urinary flow rate decreased significantly in older animals, whereas sodium excretion and free water clearance were not altered. There was an age-dependent effect on potassium handling along the nephron, potassium excretion decreasing after ZD 7155 infusion in younger but not in older lambs. PD 123319 had no significant effects on glomerular filtration rate and tubular function in either age group.ConclusionsThese results provide evidence to support an important role for AT1Rs in mediating the renal effects of angiotensin II during postnatal maturation in conscious developing animals. In contrast to a role for AT2Rs later in life, there appears to be no role for AT2Rs in influencing the renal effects of Angiotensin II in the postnatal period.Electronic supplementary materialThe online version of this article (doi:10.1186/s12899-016-0022-3) contains supplementary material, which is available to authorized users.

ANG II facilitated CD11+Ly6Chi cells reprogramming into M1-like macrophage through Erk1/2 or p38-Stat3 pathway and involved in EAM

“…However, our data at least indicated that ANG II‐AT 1 R axis played important roles in EAM development and CD11b + Ly6C + cells reprogramming. And our data also were in line with published reports that most actions of ANG II were primarily carried out by AT 1 R signaling . Additionally, inhibition of Erk1/2, p38, or Stat3 could also obviously ameliorate the cardiac injury, which cannot completely owe to prevent M1 polarization; as all these inhibitors are not specific for macrophage polarization, more and more data indicated that macrophage polarization was associated with Erk1/2, p38, or Stat3; therefore, our data suggested that to prevent the macrophage polarization, the EAM development could be ameliorated.…”

“…ANG II plays pivotal physiological or pathological roles through ligation with its specific G protein‐coupled receptors, type 1/2 receptor (AT 1 R or AT 2 R). However, most roles were carried out by AT 1 R signaling . Recently, ANG II can serve as a powerful proinflammatory mediator and involve in autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune nephritis, and experimental autoimmune encephalomyelitis as well as monocyte and macrophage recruitment .…”

Physiology and Pathophysiology of Compensatory Adaptations of a Solitary Functioning Kidney

“…Additionally, we have also demonstrated that regulation of glomerular hemodynamics by the RAS is impaired in sheep with SFK, suggesting that this may potentially be a system that can be targeted to improve renal outcomes in SFK ( Singh et al, 2011 ). Postnatal adaptive maturation of both blood pressure and glomerular filtration rate (GFR) is associated with the RAS ( Robillard et al, 1983 ; Prevot et al, 2002 ; Vinturache and Smith, 2016 ). In conscious lambs, blood pressure is low at birth and plasma renin activity is elevated but during the first 3 months of post-natal maturation, plasma renin activity decreases as blood pressure increases ( Monument and Smith, 2003 ; Velaphi et al, 2007 ).…”

“…In conscious lambs, blood pressure is low at birth and plasma renin activity is elevated but during the first 3 months of post-natal maturation, plasma renin activity decreases as blood pressure increases ( Monument and Smith, 2003 ; Velaphi et al, 2007 ). Additionally, in the early postnatal period in conscious lambs angiotensin II activation of AT1R regulates GFR and kidney injury associated with glomerular hyperfiltration and hypertrophy may be underpinned by RAS activation ( Babić et al, 2007 ; Vinturache and Smith, 2016 ).…”

The Other Angiotensin II Receptor: AT2R as a Therapeutic Target

“…These receptors selectively and specifically but differently regulate many of the cardiovascular, hemodynamic, renal, neurological, and endothelial functions, cell proliferation and survival, inflammation, and cell-matrix interactions of the RAS. For example, a more important role for AT 2 R than AT 1 R has been shown in fetal development, while AT 1 R is more involved than AT 2 R in mediating Ang II effects for renal function in the postnatal development, maturation, and adaptation. , Ang receptors are classified by their gene sequences, structures of the proteins, ligand-binding affinities, agonist and antagonist efficacies, and signal transduction mechanisms. Pharmacologically, AT 1 R is sensitive to biphenylimidazole, such as the members of the “sartan” family of ARBs, and insensitive to AT 2 R ligands such as tetrahydroimidazopyridines.…”