Angiotensin II Type 1 (AT
            <sub>1</sub>
            ) Receptor–Mediated Accumulation of Angiotensin II in Tissues and Its Intracellular Half-life In Vivo

Kats, Jorge P. van; Lannoy, Larissa M. de; Danser, A.H. Jan; Meegen, Jan R. van; Verdouw, Pieter D.; Schalekamp, M. A. D. H.

doi:10.1161/01.hyp.30.1.42

Cited by 161 publications

(140 citation statements)

References 33 publications

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“…The ex vivo half life of 125 I-Ang II in cardiac tissue at 37°C is 30 to 40 minutes. 16 Thus, the 125 I-Ang II level we measured in cardiac tissue that was frozen within 15 seconds after the 125 I-Ang I and II infusions had been stopped and the heart had been removed from the body is probably also close to the 125 I-Ang II level in vivo. Ex vivo production of Ang II may explain why endogenous cardiac Ang II, as opposed to radiolabeled Ang II, remained constant when cardiac tissue was kept at 37°C.…”

Section: Discussionmentioning

confidence: 89%

“…An earlier study 16 in which we infused 125 IAng I and 125 I-Ang II into the left cardiac ventricle of pigs provided evidence that most of the 125 I-Ang II in cardiac tissue had been accumulated by the cells via an angiotensin AT 1 type receptor-mediated process.…”

Section: Discussionmentioning

confidence: 98%

“…These losses were Ͻ10% in plasma and maximally 20% to 30% in tissue extracts. 16 In some plasma samples, the angiotensin levels were below the limit of detection. These were taken to be equal to the lower limit of detection (1.0 fmol/mL for Ang I and 0.5 fmol/mL for Ang II) to allow calculation of mean values.…”

Section: Measurements Of 125 I-labeled and Endogenous Angiotensins Inmentioning

confidence: 99%

“…3, 16 The homogenate was centrifuged at 20 000g for 25 minutes at 4°C. Ethanol in the supernatant was evaporated under constant air flow, and the remainder of the supernatant was diluted in 20 mL 1% ortho-phosphoric acid and centrifuged again at 20 000g.…”

Section: Measurements Of 125 I-labeled and Endogenous Angiotensins Inmentioning

confidence: 99%

“…16 The concentrations of intact 125 I-Ang I and 125 I-Ang II and the concentrations of intact Ang I and Ang II in the HPLC eluate fractions were measured by gamma counting and radioimmunoassay, respectively. 17 Data were not corrected for losses that occurred during extraction and separation.…”

Section: Measurements Of 125 I-labeled and Endogenous Angiotensins Inmentioning

confidence: 99%

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Angiotensin Production by the Heart

et al. 1998

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Background —Beneficial effects of ACE inhibitors on the heart may be mediated by decreased cardiac angiotensin II (Ang II) production. Methods and Results —To determine whether cardiac Ang I and Ang II are produced in situ or derived from the circulation, we infused 125 I-labeled Ang I or II into pigs (25 to 30 kg) and measured 125 I-Ang I and II as well as endogenous Ang I and II in cardiac tissue and blood plasma. In untreated pigs, the tissue Ang II concentration (per gram wet weight) in different parts of the heart was 5 times the concentration (per milliliter) in plasma, and the tissue Ang I concentration was 75% of the plasma Ang I concentration. Tissue 125 I-Ang II during 125 I-Ang II infusion was 75% of 125 I-Ang II in arterial plasma, whereas tissue 125 I-Ang I during 125 I-Ang I infusion was <4% of 125 I-Ang I in arterial plasma. After treatment with the ACE inhibitor captopril (25 mg twice daily), Ang II fell in plasma but not in tissue, and Ang I and renin rose both in plasma and tissue, whereas angiotensinogen did not change in plasma and fell in tissue. Tissue 125 I-Ang II derived by conversion from arterially delivered 125 I-Ang I fell from 23% to <2% of 125 I-Ang I in arterial plasma. Conclusions —Most of the cardiac Ang II appears to be produced at tissue sites by conversion of in situ–synthesized rather than blood-derived Ang I. Our study also indicates that under certain experimental conditions, the heart can maintain its Ang II production, whereas the production of circulating Ang II is effectively suppressed.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 98%

Section: Measurements Of 125 I-labeled and Endogenous Angiotensins Inmentioning

confidence: 99%

Section: Measurements Of 125 I-labeled and Endogenous Angiotensins Inmentioning

confidence: 99%

Section: Measurements Of 125 I-labeled and Endogenous Angiotensins Inmentioning

confidence: 99%

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Angiotensin Production by the Heart

et al. 1998

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High glucose increases extracellular matrix production in pancreatic stellate cells by activating the renin–angiotensin system

Hong

Kim

et al. 2006

J of Cellular Biochemistry

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Pancreatic stellate cells (PSCs) are involved in pancreatic inflammation and fibrosis. Recent studies have shown that blocking the renin-angiotensin system (RAS) attenuates pancreatic inflammation and fibrosis. However, there are few data about the direct effects of high glucose on extracellular matrix (ECM) protein synthesis and angiotensin II (Ang II) induction in PSCs. PSCs were isolated from male Sprague-Dawley rats and cultured in medium containing 5.5 mM (LG group) or 27 mM D-glucose (HG group). Levels of Ang II and transforming growth factor-beta (TGF-beta) in culture media were measured and Ang II-positive cells were counted. We used real-time polymerase chain reaction (PCR) to detect Ang II receptor expression and Western blot analysis for the expression of ECM proteins such as connective-tissue growth factor (CTGF) and collagen type IV. Cells were also treated with an Ang II-receptor antagonist (candesartan, 10 microM) or angiotensin-converting enzyme (ACE) inhibitor (ramiprilat, 100 nM). Thymidine uptake by PSCs increased fourfold with high glucose treatment. Ang II levels and the proportion of Ang II-positive PSCs were significantly increased after 6 h under high-glucose conditions. TGF-beta concentrations also increased significantly with high glucose. After 72 h, the expression of CTGF and collagen type IV proteins in high-glucose cultures increased significantly and this increase was effectively attenuated by the candesartan or the ramiprilat. All together, high glucose induced PSCs proliferation and ECM protein synthesis, and these effects were attenuated by an Ang II-receptor antagonist. The data suggest that pancreatic inflammation and fibrosis aggravated by hyperglycemia, and Ang II play an important role in this pathogenesis.

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Expression of endogenous nuclear bradykinin B2 receptors mediating signaling in immediate early gene activation

Savard

Barbaz

Bélanger

et al. 2008

Journal Cellular Physiology

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Bradykinin (BK) represents a pro-inflammatory mediator that partakes in many inflammatory diseases. The mechanism of action of BK is thought to be primarily mediated by specific cell surface membrane B2 receptors (B2Rs). Some evidence has suggested, however, the existence of an intracellular/nuclear B2R population. Whether these receptors are functional and contribute to BK signaling remains to be determined. In this study, by mean of Western blotting, 3D-confocal microscopy, receptor autoradiography and radioligand binding analysis, we showed that plasma membrane and highly purified nuclei from isolated rat hepatocytes contain specific B2R that bind BK. The results depicting B2R nuclear expression in isolated nuclear organelles were reproduced in situ on hepatic sections by immunogold labeling and transmission electron microscopy. Functional tests on single nuclei, by means of confocal microscopy and the calcium-sensitive probe fluo-4AM, showed that BK induces concentration-dependent transitory mobilization of nucleoplasmic calcium; these responses were blocked by B2R antagonist HOE 140, not by the B1R antagonist R954 and, were also found in wild-type C57/Bl6 mice, but not in B2R-KO mice. In isolated nuclei, BK elicited activation/phosphorylation of Akt, acetylation of histone H3 and ensuing pro-inflammatory iNOS gene induction as determined by Western blot and RT-PCR. ChIP assay confirmed binding of acetylated-histone H3 complexes, but not B2R, to promoter region of iNOS gene suggesting that B2R-mediated gene expression is bridged with accessory downstream effectors. This study discloses a previously undescribed mechanism in BK-induced transcriptional events, via intracrine B2R-mediated signaling, occurring in rat autologous hepatic cells.

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Angiotensin II Type 1 (AT ₁ ) Receptor–Mediated Accumulation of Angiotensin II in Tissues and Its Intracellular Half-life In Vivo

Cited by 161 publications

References 33 publications

Angiotensin Production by the Heart

Angiotensin Production by the Heart

High glucose increases extracellular matrix production in pancreatic stellate cells by activating the renin–angiotensin system

Expression of endogenous nuclear bradykinin B2 receptors mediating signaling in immediate early gene activation

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Angiotensin II Type 1 (AT 1 ) Receptor–Mediated Accumulation of Angiotensin II in Tissues and Its Intracellular Half-life In Vivo

Cited by 161 publications

References 33 publications

Angiotensin Production by the Heart

Angiotensin Production by the Heart

High glucose increases extracellular matrix production in pancreatic stellate cells by activating the renin–angiotensin system

Expression of endogenous nuclear bradykinin B2 receptors mediating signaling in immediate early gene activation

Contact Info

Product

Resources

About

Angiotensin II Type 1 (AT ₁ ) Receptor–Mediated Accumulation of Angiotensin II in Tissues and Its Intracellular Half-life In Vivo