Regulation of angiotensin II receptors beyond the classical pathway

2012 ◽  
Vol 123 (4) ◽  
pp. 193-203 ◽  
Author(s):  
Masatsugu Horiuchi ◽  
Jun Iwanami ◽  
Masaki Mogi
Keyword(s):  
Angiotensin Ii ◽  
Cross Talk ◽  
Receptor Activation ◽  
At1 Receptor ◽  
Receptor Subtypes ◽  
Peroxisome Proliferator ◽  
Classical Pathway ◽  
At2 Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Metabolic Syndrome

The RAS (renin–angiotensin system) plays a role not only in the cardiovascular system, including blood pressure regulation, but also in the central nervous system. AngII (angiotensin II) binds two major receptors: the AT1 receptor (AngII type 1 receptor) and AT2 receptor (AngII type 2 receptor). It has been recognized that AT2 receptor activation not only opposes AT1 receptor actions, but also has unique effects beyond inhibitory cross-talk with AT1 receptor signalling. Novel pathways beyond the classical actions of RAS, the ACE (angiotensin-converting enzyme)/AngII/AT1 receptor axis, have been highlighted: the ACE2/Ang-(1–7) [angiotensin-(1–7)]/Mas receptor axis as a new opposing axis against the ACE/AngII/AT1 receptor axis, novel AngII-receptor-interacting proteins and various AngII-receptor-activation mechanisms including dimer formation. ATRAP (AT1-receptor-associated protein) and ATIP (AT2-receptor-interacting protein) are well-characterized AngII-receptor-associated proteins. These proteins could regulate the functions of AngII receptors and thereby influence various pathophysiological states. Moreover, the possible cross-talk between PPAR (peroxisome-proliferator-activated receptor)-γ and AngII receptor subtypes is an intriguing issue to be addressed in order to understand the roles of RAS in the metabolic syndrome, and interestingly some ARBs (AT1-receptor blockers) have been reported to have an AT1-receptor-blocking action with a partial PPAR-γ agonistic effect. These emerging concepts concerning the regulation of AngII receptors are discussed in the present review.

scholarly journals Angiotensin II Dilates Bovine Adrenal Cortical Arterioles: Role of Endothelial Nitric Oxide

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3319-3324 ◽  
Author(s):  
Kathryn M. Gauthier ◽  
David X. Zhang ◽  
Erik M. Edwards ◽  
Blythe Holmes ◽  
William B. Campbell
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Receptor Activation ◽  
At1 Receptor ◽  
Internal Diameter ◽  
No Production ◽  
At2 Receptor ◽  
Angiotensin Type

Abstract Adrenal steroidogenesis is modulated by humoral and neuronal factors and blood flow. Angiotensin II (AII) stimulates adrenal cortical aldosterone and cortisol production and medullary catecholamine release. However, AII regulation of adrenal vascular tone has not been characterized. We examined the effect of AII on diameters of cannulated bovine adrenal cortical arteries. Cortical arteries (average internal diameter = 230 μm) were constricted with U46619 and concentration-diameter responses to AII (10−13 to 10−8 mol/liter) were measured. In endothelium-intact arteries, AII induced dilations at low concentrations (maximum dilation = 25 ± 6% at 10−10 mol/liter) and constrictions at high concentrations (maximum constriction = 25 ± 18% at 10−8 mol/liter). AII constrictions were blocked by the angiotensin type 1 (AT1) receptor antagonist, losartan (10−6 mol/liter). AII dilations were enhanced by losartan (maximal dilation = 48 ± 8%), abolished by endothelial cell removal or N-nitro-l-arginine (L-NA, 3 × 10−5 mol/liter) and inhibited by the angiotensin type 2 (AT2) receptor antagonist, PD123319 (10−6 mol/liter, maximal dilation = 18 ± 4%). In a 4,5-diaminofluorescein diacetate nitric oxide (NO) assay of isolated cortical arteries, AII stimulated NO production, which was abolished by PD123319, L-NA, or endothelial cell removal. Western immunoblot of arterial homogenates and endothelial and zona glomerulosa cell lysates revealed 48-kD and 50-kD bands corresponding to AT1 and AT2 receptors, respectively, in all three and a 140-kD band corresponding to endothelial NO synthase in endothelial cells and arteries. Our results demonstrate that AII stimulates adrenal cortical arterial dilation through endothelial cell AT2 receptor activation and NO release and AT1 receptor-dependent constriction.

scholarly journals Characterisation of angiotensin II receptors in isolated human subcutaneous resistance arteries

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S37-S41 ◽  
Author(s):  
Hoa Ytterberg ◽  
Lars Edvinsson
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
At1 Receptor ◽  
Receptor Subtypes ◽  
At2 Receptor ◽  
Ang Ii ◽  
Resistance Arteries ◽  
Receptor Antagonists ◽  
Response Curves ◽  
At1 Receptor Antagonists

Subcutaneous arteries have been used as a model for resistance arteries, which are potentially involved in enhanced blood pressure (BP) regulation in man. Angiotensin II (Ang II) is an important regulator of tone, acting via type 1 (AT1-) and type 2 (AT2-) receptor subtypes. The aim of this study was to characterise the Ang II receptors in isolated human subcutaneous arteries, using pharmacological and molecular methods. Subcutaneous arteries were obtained from patients undergoing elective gut surgery and were carefully dissected from the abdominal wall. Cylindrical segments were mounted on two L-shaped metal prongs, one of which was connected to a force-displacement transducer for continuous recording of isometric tension. Concentration-response curves to Ang II were constructed in the presence and absence of various selective AT1-receptor antagonists, candesartan, EXP3174, irbesartan and losartan, and the AT2-receptor antagonist, PD 123319. Responses to Ang II were measured as increases in force (mN) and expressed as a percentage of the response to 60 mM of KCl. Ang II caused a concentration-dependent contraction (pEC50=9.45±0.48, Emax=120±13%). Candesartan and EXP3174 caused concentration-dependent depression of the Emax of Ang II without any major shift of pEC50. Losartan and irbesartan caused a significant, dose-dependent rightward shift of the Ang II contraction-response curve in human subcutaneous arteries. The results show that contractile responses of human subcutaneous arteries are mediated via the AT1-receptor. The AT1-receptor antagonists, candesartan and EXP3174, acted in an insurmountable manner, while losartan and irbesartan were surmountable AT1-receptor antagonists. The AT2-receptor antagonist, PD 123319, (10, 100 nM) had no effect on Ang II-induced contraction. This is supported by the positive identification of mRNA for the human AT 1-receptor by RT-PCR.

scholarly journals Peroxisome Proliferator-Activated Receptor Activation is Associated with Altered Plasma One-Carbon Metabolites and B-Vitamin Status in Rats

Nutrients ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 26 ◽  
Author(s):  
Vegard Lysne ◽  
Elin Strand ◽  
Gard Svingen ◽  
Bodil Bjørndal ◽  
Eva Pedersen ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Vitamin Status ◽  
B Vitamin
Sign in / Sign up

Export Citation Format

Share Document