Abstract P284: Angiotensin II Upregulates Cytochrome-450 4A Expression in Rat Kidney Through Type 1 Receptor

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Wanting Wang ◽  
Rong Rong ◽  
Osamu Ito ◽  
Yoshiko Ogawa ◽  
Yoshikazu Muroya ◽  
...  
Keyword(s):  
Renal Cortex ◽  
Urinary Albumin Excretion ◽  
Rat Kidney ◽  
At1 Receptor ◽  
Urinary Albumin ◽  
High Dose ◽  
At2 Receptor ◽  
Ang Ii ◽  
Outer Medulla

20-hydroxyeicosatetraenoic acids (20-HETE) is a cytochrome P-450 (CYP) 4A-dependent metabolite of arachidonic acid and regulates vascular tone and renal tubular function. Previous studies showed that angiotensin II (Ang II) stimulated the renal CYP activity and 20-HETE production through the Ang II type 1 (AT1) receptor and that the Ang II-increased the 20-HETE was linked to the Ang II type 2(AT2) receptor. Thus, the study was designed to clarify the role of Ang II in CYP4A isoforms expression in the rat kidney. Male Sprague-Dawley rats were infused Ang II at low dose (AL, 0.17mg/kg/min, sc) and high dose (AH, 0.70mg/kg/day, sc) by using osmotic mini pump, with or without AT1 receptor blocker candesartan (1 and 3mg/kg/day, po) for 1 week. The protein expression of CYP4A isoforms, AT1 receptor and AT2 receptor in the renal cortex, outer medulla, and inner medulla was examined by immunoblot analysis. The mRNA expression of CYP4A isoforms was examined by reverse transcription and polymerase chain reaction (RT-PCR). Ang II at high dose increased systolic blood pressure (control, 109±2; AH, 164±8 mmHg, p<0.01), creatinine (control, 0.24±0.00; AH, 0.29±0.01 mg/dl, p<0.01) and urinary albumin excretion (control, 20.3±5.9; AH, 2398.6±303.6 μg/mg creatinine, p<0.01). In the control group, the CYP4A1, 4A2, and 4A8 proteins were highly expressed in the renal cortex, lowly expressed in the outer medulla, barely detected in the inner medulla. The AT1 receptor was expressed in kidney sections; highly in the outer and inner medulla, the AT2 receptor was only detected in the outer medulla. Ang II dose-dependently increased all CYP4A isoform proteins in the renal cortex and outer medulla (CYP4A1, 24% and 222%; CYP4A2, by 51% and 258%; CYP4A8, by 52% and 550%, p<0.05). Ang II also increased all CYP4A isoform mRNAs in the renal cortex and outer medulla. The candesartan treatment dose-dependently inhibited the Ang II-increased blood pressure, creatinine, urinary albumin excretion and CYP4A isoform expressions. These results indicated that Ang II increases CYP4A isoform expressions in the kidney through AT1 receptor. The Ang II-upregulated CYP4A expressions may play an important role in hypertension and renal function.

Localization of angiotensin II type 1 receptor subtype mRNA in rat kidney

1995 ◽  
Vol 268 (2) ◽  
pp. F220-F226 ◽  
Author(s):  
D. P. Healy ◽  
M. Q. Ye ◽  
M. Troyanovskaya
Keyword(s):  
In Situ Hybridization ◽  
Rat Kidney ◽  
At1 Receptor ◽  
Receptor Subtypes ◽  
Mrna Levels ◽  
Ang Ii ◽  
Outer Medulla ◽  
Vasa Recta

The physiological effects of angiotensin II (ANG II) on the kidney are mediated primarily by the ANG II type 1 (AT1) receptor. Two highly similar AT1 receptor subtypes have been identified in the rat by molecular cloning techniques, namely AT1A and AT1B. The intrarenal localization of the AT1A and AT1B receptor subtypes has not been studied by hybridization methods with subtype-specific receptor probes. Using radiolabeled probes from the 3' noncoding region of the AT1A and AT1B cDNAs, we localized AT1 mRNA in rat kidney by in situ hybridization. Specificity of the 3' noncoding region probes was tested by Northern blot and solution hybridization methods. AT1A mRNA levels were highest in the liver, kidney, and adrenal. In contrast, AT1B mRNA levels were highest in the adrenal and pituitary and low in kidney. Autoradiographic localization of 125I-[Sar1,Ile8]ANG II binding indicated that the highest levels of AT1 receptors were found in glomeruli and vascular elements. In situ hybridization with a nonselective AT1 receptor riboprobe indicated that the highest levels of AT1 mRNA were in the outer medullary vasa recta and cortical glomeruli with additional diffuse labeling of the cortex and outer medulla, consistent with labeling of tubular elements. In contrast, in situ hybridization with the AT1 subtype selective probes revealed that AT1A receptor mRNA was primarily localized to the vasa recta and diffusely to the outer stripe of the outer medulla and the renal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Receptor AT1 Appears to Be Important for the Maintenance of Bone Mass and AT2 Receptor Function in Periodontal Bone Loss Appears to Be Regulated by AT1 Receptor

2021 ◽  
Vol 22 (23) ◽  
pp. 12849
Author(s):  
Maria Laura de Souza Lima ◽  
Agnes Andrade Martins ◽  
Caroline Addison Carvalho Xavier de Medeiros ◽  
Gerlane Coelho Bernardo Guerra ◽  
Robson Santos ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Alveolar Bone ◽  
Experimental Studies ◽  
At1 Receptor ◽  
At2 Receptor ◽  
Ang Ii ◽  
Key Events

A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.

Angiotensin II hypertension is attenuated in interleukin-6 knockout mice

2006 ◽  
Vol 290 (3) ◽  
pp. H935-H940 ◽  
Author(s):  
Dexter L. Lee ◽  
Lashon C. Sturgis ◽  
Hicham Labazi ◽  
James B. Osborne ◽  
Cassandra Fleming ◽  
...  
Keyword(s):  
Urinary Albumin Excretion ◽  
Control Period ◽  
Urinary Albumin ◽  
High Salt ◽  
Sodium Balance ◽  
High Dose ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet ◽  
Albumin Excretion

Plasma levels of IL-6 correlate with high blood pressure under many circumstances, and ANG II has been shown to stimulate IL-6 production from various cell types. This study tested the role of IL-6 in mediating the hypertension caused by high-dose ANG II and a high-salt diet. Male C57BL6 and IL-6 knockout (IL-6 KO) mice were implanted with biotelemetry devices and placed in metabolic cages to measure mean arterial pressure (MAP), heart rate (HR), sodium balance, and urinary albumin excretion. Baseline MAP during the control period averaged 114 ± 1 and 109 ± 1 mmHg for wild-type (WT) and IL-6 KO mice, respectively, and did not change significantly when the mice were placed on a high-salt diet (HS; 4% NaCl). ANG II (90 ng/min sc) caused a rapid increase in MAP in both groups, to 141 ± 9 and 141 ± 4 in WT and KO mice, respectively, on day 2. MAP plateaued at this level in KO mice (134 ± 2 mmHg on day 14 of ANG II) but began to increase further in WT mice by day 4, reaching an average of 160 ± 4 mmHg from days 10 to 14 of ANG II. Urinary albumin excretion on day 4 of ANG II was not different between groups (9.18 ± 4.34 and 8.53 ± 2.85 μg/2 days for WT and KO mice). By day 14, albumin excretion was nearly fourfold greater in WT mice, but MAP dropped rapidly back to control levels in both groups when the ANG II was stopped after 14 days. Thus the ∼30 mmHg greater ANG II hypertension in the WT mice suggests that IL-6 contributes significantly to ANG II-salt hypertension. In addition, the early separation in MAP, the albumin excretion data, and the rapid, post-ANG II recovery of MAP suggest an IL-6-dependent mechanism that is independent of renal injury.

scholarly journals Development of salt-sensitive hypertension in a sensory denervated model: the underlying mechanisms

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S125-S129 ◽  
Author(s):  
Donna H Wang ◽  
Yan Huang
Keyword(s):  
Renal Cortex ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Male Rats ◽  
At2 Receptor ◽  
Ang Ii ◽  
High Sodium ◽  
Sodium Diet ◽  
Salt Sensitive Hypertension ◽  
High Sodium Diet

We use a novel salt-sensitive hypertensive model recently developed in our laboratory. This model shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to a salt load with a significant rise in blood pressure (BP). To test the hypothesis that development of salt-sensitive hypertension in sensory denervated rats is mediated by abnormal regulation of both circulating and tissue renin-angiotensin systems (RAS), neonatal Wistar rats were given capsaicin, 50 mg/kg s.c., on the first and second days of life. Control rats were treated with vehicle solution. After the weaning period, male rats were divided into four groups and subjected to the following treatments for three weeks: control + high sodium diet (4%, CON-HS), capsaicin pretreatment + normal sodium diet (0.5%, CAP-NS), capsaicin pretreatment + high sodium diet (CAP-HS), and capsaicin pretreatment + high sodium diet + candesartan cilexetil (10 mg/kg/per day, CAP-HS-CAN). Radioimmunoassay shows that plasma renin activity (ng/ml/hr, PRA) was higher in CAP-NS (2.58±0.17) than in CON-HS (0.14±0.03) and CAP-HS (0.74±0.15), and it was higher in CAP-HS than in CON-HS (p<0.05). Western blot analysis shows that expression of the angiotensin II (Ang II) type 1 (AT1) receptor in both the renal cortex and outer medulla was higher in CAP-HS than in CON-HS and CAP-NS rats (p<0.05). Expression of the Ang II type 2 (AT2) receptor in the renal cortex was higher in both CAP-HS and CAP-NS than in CON-HS rats (p<0.05), but there was no difference in AT2-receptor expression in the renal medulla between CAP-HS, CAP-NS, and CON-HS rats. Likewise, there was no difference in AT1-receptor expression in mesenteric resistance arteries between CAP-HS, CAP-NS, and CON-HS rats. In contrast, mesenteric AT2-receptor expression was lower in CAP-HS than in CAP-NS and CON-HS rats (p<0.05). Tail-cuff systolic BP (mmHg) shows that blockade of the AT1-receptor with candesartan prevents the development of hypertension in CAP-HS rats (by the end of the experiment, CON-HS, 122±3; CAP-NS, 118±10; CAP-HS, 169±9; CAP-HS-CAN, 129±2, p<0.05). Thus, both circulating and tissue RAS in sensory-denervated rats are abnormally regulated in response to a high-salt intake, which may contribute to increased salt sensitivity and account for the effectiveness of candesartan in lowering BP in this model.

scholarly journals INSULIN DEPENDENT DIABETES MELLITUS

2009 ◽  
Vol 16 (02) ◽  
pp. 178-186
Author(s):  
MUHAMMAD USMAN KHURSHID ◽  
MANSOOR-UL-HASSAN ALV I
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Sialic Acid ◽  
Urinary Albumin Excretion ◽  
Microvascular Complications ◽  
Urinary Albumin ◽  
Elevated Plasma ◽  
Albumin Excretion

A i m s & O b j e c t i v e s : To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acutephaseresponse, is related to the presence of diabetic retinopathy in type 1 diabetes mellitus or Insulin Dependant Diabetes Mellitus (IDDM).R e s e a r c h D e s i g n a n d M e t h o d s : We investigated the relationship between plasma sialic acid concentration and diabetic retinopathy in across-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the IDDM Complications Study, which involveddiabetic centers of four different hospitals in Lahore. Results: There was a significantly increasing trend of plasma sialic acid with severityof retinopathy (P < 0.001 in men) and with degree of urinary albumin excretion (P < 0.001 men, P < 0.01 women). Elevated plasma sialicacid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbAlc, plasma triglycerideand cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiplelogistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate inmen. Conclusions: We concluded that an elevated plasma sialic concentration is strongly related to the presence of microvascularcomplications in type 1 diabetes with retinopathy and nephropathy. Further study of acute-phase response markers and mediators asindicators or predictors of diabetic microvascular complications is therefore justified.

Abstract P219: Losartan Prevents The Recruitment Of Renal M1-like Macrophages And Dendritic Cells In Medulla Of Angiotensin Ii Hypertensive Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Patricio A Araos ◽  
Andrés Guzmán ◽  
Stefanny M Figueroa ◽  
Javier Reyes ◽  
Cristián A Amador
Keyword(s):  
Dendritic Cells ◽  
Immune Cells ◽  
Renal Cortex ◽  
Renal Medulla ◽  
Ang Ii ◽  
Mhc Ii ◽  
Treatment Changes ◽  
Antigen Presenting

Immune cells play a major role in the development and progression of hypertension. Previous studies have shown that antigen presenting cells (APCs), such as macrophages (Mø) and dendritic cells (DCs) are particularly abundant in kidney. However, the relevance of these renal APCs on hypertension and whether their distribution change during the anti-hypertensive treatment remain unknow. We evaluated whether losartan (Los) treatment changes the abundance of APCs in the renal cortex and medulla in Angiotensin (Ang) II-infused mice.Male C57BL/6 mice (8-12wo) were treated with AngII (490ng/Kg/min), AngII+Los (20mg/Kg/day) or Vehicle for 14 days (n=4-6). Systolic blood pressure (SBP) was measured by the tail cuff method, and renal cortex/medulla were isolated for the measurements of: APCs (MHC-II + :CD11c + ), DCs (APCs:F4/80 - :CD64 - /CD103 + for type-1 DCs, or APCs:F4/80 - :CD64 - :CD11b + for type-2 DCs), and M1-like Mø (APCs:F4/80 - :CD64 + :CD11b + ), by flow cytometry.Los treatment prevented the increased SBP (AngII+Los=118.8±6.4 mmHg vs. AngII=158.0±21.1 mmHg; p<0.001), and the APCs recruitment in renal cortex (AngII+Los=23.2±2.7 vs. AngII=36.0±5.9%; p<0.01) and in renal medulla (Veh=16.3±7.7; AngII=26.3±4,7; AngII+Los=14.9±3.3%; p<0.05) induced by AngII. In addition, we observed an increase of DC2 and M1-like Mø recruitments in renal medulla of AngII mice (DC2 Veh =29.0±5.0 vs. DC2 AngII =45.5±7.3%; p<0.05; M1 Veh =44.8±7.5 vs. M1 AngII =58.3±5.3%; p<0.05), which were prevented by Los treatment (DC2 AngII+Los =27.1±6.8%; p<0.05; M1 AngII+Los =47.0±3.5%; p<0.05). Interestingly, we did not observe differences between groups on M1-like Mø, and DC2 populations in renal cortex. However, Los treatment prevented the increase of DC1 on renal cortex (Veh=2.1±1.4; AngII=5.2±2.4; AngII+Los=2.1±0.8%; p<0.05), without differences between groups at medullar level.Our results show that Los treatment has a differential effect on the APCs populations in renal cortex and medulla, suggesting that renal APCs have different participations on hypertension according their microenvironment.Supported by Fondecyt #1201251 and #3201016

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