Angiotensin II Attenuates Vasodilatation Induced by No-Donor, Glyceryl Trinitrate: Role of Super Oxide and Angiotensin Type 1 Receptor

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 696-697
Author(s):  
Atsushi Wada ◽  
Shinichiro Ueda ◽  
Satoko Masumori-Maemoto ◽  
Naomitsu Kuji ◽  
Satoshi Umemura
Keyword(s):  
Angiotensin Ii ◽  
Vitamin C ◽  
Glyceryl Trinitrate ◽  
Ang Ii ◽  
Arterial Infusion ◽  
No Donor ◽  
Vasodilating Effect ◽  
Angiotensin Type

P25 We investigated effects of subpressor dose of angiotensin II (ANG II) on the vasodilating effect of Glyceryl trinitrate (GTN)in 9 normotensive healthy males. GTN at 100, 250, 1000 ng/min was intra-arterially infused with ANG II at 1, 5 pmol/min or placebo (protocol 1) with noradrenaline (NA) at 50 pmol/min or placebo (protocol 2). Effect of intra-arterial infusion of vitamin C at 25 mg/min on the interaction between GTN and ANG II was also tested (protocol 3).Protocol 1 was repeated after single oral dose of angiotensin type 1 receptor blocker, Candesartan (8mg) or matched placebo (protocol 4). Forearm blood flow (FBF) was measured by strain gauge plethymograph. ANG II significantly and dose-dependently attenuated the vasodilating effect of GTN (means±S.D. of % changes of FBF: 28±8, 79±22, 208±28 % at 100, 250, 1000 pmol/min of GTN with placebo, 8±6, 47±13, 173±31 with ANG II 1 pmol/min, 2±10, 39±13, 132±23 with ANG II 5 pmol/min. P=0.0057 vs placebo by ANOVA).NA did not affect the vasodilating effect of GTN. Co-infusion of vitamin C (25 mg/min)completely abolished the the interaction between ANG II and GTN. Attenuation of the effect of GTN by ANG II disappeared after the single dose of Candesartan. In summary, subpressor dose of ANG II attenuated the effect of GTN. There was a lack of effect of ANG II in the presence of either vitamin C or Candesartan. Our results suggest that ANG II may stimulate superoxide production through AT1 receptor which inactivates NO by forming peroxynitrite.

Reactive Oxygen Species-Mediated Homologous Downregulation of Angiotensin II Type 1 Receptor Mrna by Angiotensin II

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 688-688
Author(s):  
Toshihiro Ichiki ◽  
Kotaro Takeda ◽  
Akira Takeshita
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Crucial Role ◽  
Oxygen Species ◽  
Ang Ii ◽  
Stimulation Of

58 Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of Angiotensin II (Ang II) through type 1 Ang II receptor (AT1-R). However, the role of ROS in the regulation of AT1-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT1-R by Ang II. Ang II (10 -6 mol/L) decreased AT1-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells (VSMC). Ang II dose-dependently (10 -8 -10 -6 ) suppressed AT1-R mRNA at 6 hours of stimulation. Preincubation of VSMC with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II-induced downregulation of AT1-R mRNA. The effect of NAC was due to stabilization of the AT1-R mRNA that was destabilized by Ang II. Ang II did not affect the promoter activity of AT1-R gene. Diphenylene iodonium (DPI), an inhibitor of NADH/NADPH oxidase failed to inhibit the Ang II-induced AT1-R mRNA downregulation. The Ang II-induced AT1-R mRNA downregulation was also blocked by PD98059, an extracellular signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK activation was inhibited by NAC as well as PD98059 whereas DPI did not inhibit it. To confirm the role of ROS in the regulation of AT1-R mRNA expression, VSMC were stimulated with H 2 O 2 . H 2 O 2 suppressed the AT1-R mRNA expression and activated ERK. These results suggest that production of ROS and activation of ERK are critical for downregulation of AT1-R mRNA. The differential effect of NAC and DPI on the downregulation of AT1-R mRNA may suggest the presence of other sources than NADH/NADPH oxidase pathway for ROS in Ang II signaling. Generation of ROS through stimulation of AT1-R not only mediates signaling of Ang II but may play a crucial role in the adaptation process of AT1-R to the sustained stimulation of Ang II.

Angiotensin II type 2 receptor (AT2R) in renal and cardiovascular disease

2016 ◽  
Vol 130 (15) ◽  
pp. 1307-1326 ◽  
Author(s):  
Bryna S.M. Chow ◽  
Terri J. Allen
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Cellular Growth ◽  
Receptor Subtype ◽  
Electrolyte Balance ◽  
Ang Ii ◽  
Biological Responses

Angiotensin II (Ang II) is well-considered to be the principal effector of the renin–angiotensin system (RAS), which binds with strong affinity to the angiotensin II type 1 (AT1R) and type 2 (AT2R) receptor subtype. However, activation of both receptors is likely to stimulate different signalling mechanisms/pathways and produce distinct biological responses. The haemodynamic and non-haemodynamic effects of Ang II, including its ability to regulate blood pressure, maintain water–electrolyte balance and promote vasoconstriction and cellular growth are well-documented to be mediated primarily by the AT1R. However, its biological and functional effects mediated through the AT2R subtype are still poorly understood. Recent studies have emphasized that activation of the AT2R regulates tissue and organ development and provides in certain context a potential counter-regulatory mechanism against AT1R-mediated actions. Thus, this review will focus on providing insights into the biological role of the AT2R, in particular its actions within the renal and cardiovascular system.

scholarly journals Functional role of sodium glucose transporter in high glucose-mediated angiotensin type 1 receptor downregulation in human proximal tubule cells

2012 ◽  
Vol 303 (5) ◽  
pp. F766-F774 ◽  
Author(s):  
Rekha Yesudas ◽  
Russell Snyder ◽  
Thomas Abbruscato ◽  
Thomas Thekkumkara
Keyword(s):  
Proximal Tubule ◽  
Glucose Uptake ◽  
High Glucose ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Ang Ii ◽  
Angiotensin Type ◽  
Human Proximal Tubule

Previously, we have demonstrated human angiotensin type 1 receptor (hAT1R) promoter architecture with regard to the effect of high glucose (25 mM)-mediated transcriptional repression in human proximal tubule epithelial cells (hPTEC; Thomas BE, Thekkumkara TJ. Mol Biol Cell 15: 4347–4355, 2004). In the present study, we investigated the role of glucose transporters in high glucose-mediated hAT1R repression in primary hPTEC. Cells were exposed to normal glucose (5.5 mM) and high glucose (25 mM), followed by determination of hyperglycemia-mediated changes in receptor expression and glucose transporter activity. Exposure of cells to high glucose resulted in downregulation of ANG II binding (4,034 ± 163.3 to 1,360 ± 154.3 dpm/mg protein) and hAT1R mRNA expression (reduced 60.6 ± 4.643%) at 48 h. Under similar conditions, we observed a significant increase in glucose uptake (influx) in cells exposed to hyperglycemia. Our data indicated that the magnitude of glucose influx is concentration and time dependent. In euglycemic cells, inhibiting sodium-glucose cotransporters (SGLTs) with phlorizin and facilitative glucose transporters (GLUTs) with phloretin decreased glucose influx by 28.57 ± 0.9123 and 54.33 ± 1.202%, respectively. However, inhibiting SGLTs in cells under hyperglycemic conditions decreased glucose influx by 53.67 ± 2.906%, while GLUT-mediated glucose uptake remained unaltered (57.67 ± 3.180%). Furthermore, pretreating cells with an SGLT inhibitor reversed high glucose-mediated downregulation of the hAT1R, suggesting an involvement of SGLT in high glucose-mediated hAT1R repression. Our results suggest that in hPTEC, hyperglycemia-induced hAT1R downregulation is largely mediated through SGLT-dependent glucose influx. As ANG II is an important modulator of hPTEC transcellular sodium reabsorption and function, glucose-mediated changes in hAT1R gene expression may participate in the pathogenesis of diabetic renal disease.

scholarly journals Intrarenal angiotensin II and angiotensinogen augmentation in chronic angiotensin II-infused mice

2008 ◽  
Vol 295 (3) ◽  
pp. F772-F779 ◽  
Author(s):  
Romer A. Gonzalez-Villalobos ◽  
Dale M. Seth ◽  
Ryousuke Satou ◽  
Heather Horton ◽  
Naro Ohashi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Low Dose ◽  
Mouse Kidney ◽  
High Dose ◽  
Ang Ii ◽  
Rt Pcr ◽  
Expression Studies ◽  
Tail Cuff

The objectives of this study were to determine the effects of chronic angiotensin II (ANG II) infusions on ANG II content and angiotensinogen expression in the mouse kidney and the role of the angiotensin II type 1 receptor (AT1R) in mediating these changes. C57BL/6J male mice were subjected to ANG II infusions at doses of 400 or 1,000 ng·kg−1·min−1 either alone or with an AT1R blocker (olmesartan; 3 mg·kg−1·day−1) for 12 days. Systolic and mean arterial pressures were determined by tail-cuff plethysmography and radiotelemetry. On day 13, blood and kidneys were collected for ANG II determinations by radioimmunoanalysis and intrarenal angiotensinogen expression studies by quantitative RT-PCR, Western blotting, and immunohistochemistry. ANG II infusions at the low dose elicited progressive increases in systolic blood pressure (135 ± 2.5 mmHg). In contrast, the high dose induced a rapid increase (152 ± 2.5, P < 0.05 vs. controls, 109 ± 2.8). Renal ANG II content was increased by ANG II infusions at the low dose (1,203 ± 253 fmol/g) and the high dose (1,258 ± 173) vs. controls (499 ± 40, P < 0.05). Kidney angiotensinogen mRNA and protein were increased only by the low dose to 1.13 ± 0.02 and 1.26 ± 0.10, respectively, over controls (1.00, P < 0.05). These effects were not observed in mice infused at the high dose and those receiving olmesartan. The results indicate that chronic ANG II infusions augment mouse intrarenal ANG II content with AT1R-dependent uptake occurring at both doses, but only the low dose of infusion, which elicited a slow progressive response, causes an AT1R-dependent increase in intrarenal angiotensinogen expression.

Angiotensin II attenuates the vasodilating effect of a nitric oxide donor, glyceryl trinitrate: Roles of superoxide and angiotensin II type 1 receptors*

2002 ◽  
Vol 71 (6) ◽  
pp. 440-447 ◽  
Author(s):  
Atsushi Wada ◽  
Shinichiro Ueda ◽  
Satoko Masumori-Maemoto ◽  
Naomitsu Kuji ◽  
Koh-ichi Sugimoto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Glyceryl Trinitrate ◽  
Nitric Oxide Donor ◽  
Vasodilating Effect

Intracellular angiotensin II induces cell proliferation independent of AT1 receptor

2006 ◽  
Vol 291 (5) ◽  
pp. C995-C1001 ◽  
Author(s):  
Kenneth M. Baker ◽  
Rajesh Kumar
Keyword(s):  
Cell Proliferation ◽  
Angiotensin Ii ◽  
Cho Cells ◽  
Cardiac Myocyte ◽  
Chinese Hamster ◽  
Cell Types ◽  
Growth Effect ◽  
Ang Ii

We recently reported intracrine effects of angiotensin II (ANG II) on cardiac myocyte growth and hypertrophy that were not inhibited by the ANG II type 1 receptor (AT1) antagonist, losartan. To further determine the role of AT1 in intracrine effects, we studied the effect of intracellular ANG II (iANG II) on cell proliferation in native Chinese hamster ovary (CHO) cells and those stably transfected with AT1 receptor (CHO-AT1). CHO-AT1, but not CHO cells, showed enhanced proliferation following exposure to extracellular ANG II (eANG II). However, when transiently transfected with an iANG II expression vector, both cell types showed significantly enhanced proliferation, compared with those transfected with a scrambled peptide. Losartan blocked eANG II-induced cell proliferation, but not that induced by iANG II. To further confirm these findings, CHO and CHO-AT1 cells were stably transfected for iANG II expression (CHO-iA and CHO-AT1-iA, respectively). Cells grown in serum-free medium were counted every 24 h, up to 72 h. CHO-iA and CHO-AT1-iA cells showed a steeper growth curve compared with CHO and CHO-AT1, respectively. These observations were confirmed by Wst-1 assay. The AT1 receptor antagonists losartan, valsartan, telmisartan, and candesartan did not attenuate the faster growth rate of CHO-iA and CHO-AT1-iA cells. eANG II showed an additional growth effect in CHO-AT1-iA cells, which could be selectively blocked by losartan. These data demonstrate that intracrine ANG II can act independent of AT1 receptors and suggest novel intracellular mechanisms of action for ANG II.

Role of 12-lipoxygenase in decreasing P-cadherin and increasing angiotensin II type 1 receptor expression according to glomerular size in type 2 diabetic rats

2011 ◽  
Vol 300 (4) ◽  
pp. E708-E716 ◽  
Author(s):  
Qiao-Yan Guo ◽  
Li-Ning Miao ◽  
Bing Li ◽  
Fu-Zhe Ma ◽  
Nian Liu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Diabetic Rats ◽  
Ang Ii ◽  
Direct Infusion ◽  
Protein Expressions ◽  
12 Lipoxygenase ◽  
Type 2 Diabetic

12-lipoxygenase (12-LO) was implicated in the development of diabetic nephropathy (DN), in which the proteinuria was thought to be associated with a decreased expression of glomerular P-cadherin. Therefore, we investigated the role of 12-LO in the glomerular P-cadherin expression in type 2 diabetic rats according to the glomerular sizes. Rats fed with high-fat diet for 6 wk were treated with low-dose streptozotocin. Once diabetes onset, diabetic rats were treated with 12-LO inhibitor cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC) for 8 wk. Then glomeruli were isolated from diabetic and control rats with a sieving method. RT-PCR, Western blotting, and immunofluorescent staining were used for mRNA and protein expressions of P-cadherin and angiotensin II (Ang II) type 1 receptor (AT1). We found that CDC did not affect the glucose levels but completely attenuated diabetic increases in glomerular volume and proteinuria. Diabetes significantly decreased the P-cadherin mRNA and protein expressions and increased the AT1 mRNA and protein expressions in the glomeruli. These changes were significantly prevented by CDC and recaptured by direct infusion of 12-LO product [12(S)-HETE] to normal rats for 7 days. The decreased P-cadherin expression was similar between large and small glomeruli, but the increased AT1 expression was significantly higher in the large than in the small glomeruli from diabetic and 12(S)-HETE-treated rats. Direct infusion of normal rats with Ang II for 14 days also significantly decreased the glomerular P-cadherin expression. These results suggest that diabetic proteinuria is mediated by the activation of 12-LO pathway that is partially attributed to the decreased glomerular P-cadherin expression.

The angiotensin II type 2 receptor: an enigma with multiple variations

2000 ◽  
Vol 278 (3) ◽  
pp. E357-E374 ◽  
Author(s):  
Stefan Gallinat ◽  
Silke Busche ◽  
Mohan K. Raizada ◽  
Colin Sumners
Keyword(s):  
Angiotensin Ii ◽  
Singular Function ◽  
Ang Ii ◽  
Experimental Approaches ◽  
Number Of Publications ◽  
Cardiovascular Functions ◽  
Made In

Since it was discovered ten years ago, the angiotensin II (ANG II) type 2 (AT2) receptor has been an enigma. This receptor binds ANG II with a high affinity but is not responsible for mediating any of the classical physiological actions of this peptide, all of which involve the ANG II type 1 (AT1) receptor. Furthermore, the AT2 receptor exhibits dramatic differences in biochemical and functional properties and in patterns of expression compared with the AT1 receptor. During the past decade, much information has been gathered about the AT2 receptor, and the steadily increasing number of publications indicates a growing interest in this new and independent area of research. A number of studies suggest a role of AT2 receptors in brain, renal, and cardiovascular functions and in the processes of apoptosis and tissue regeneration. Despite these advances, nothing stands out as the major singular function of these receptors. The study of AT2 receptors has reached a crossroads, and innovative approaches must be considered so that unifying mechanisms as to the function of these unique receptors can be put forward. In this review we will discuss the advances that have been made in understanding the biology of the AT2receptor. Furthermore, we will consider how these discoveries, along with newer experimental approaches, may eventually lead to the elusive physiological and pathophysiological functions of these receptors.

Sign in / Sign up

Export Citation Format

Share Document