Angiotensin II Relaxations of Bovine Adrenal Cortical Arteries

Gauthier, Kathryn M.; Zhang, David X.; Cui, Lijie; Nithipatikom, Kasem; Campbell, William B.

doi:10.1161/hypertensionaha.107.104158

Cited by 13 publications

(10 citation statements)

References 31 publications

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“…Ang (1-7) was a 1000-fold less potent than Ang II in relaxing adrenal arteries. Ang (1-7)-induced relaxations are mediated by stimulation of endothelial Mas receptors and the release of NO (37). In the current study, the ACE2 inhibitor DX-600 enhanced the relaxation response to Ang II in adrenal arteries.…”

Section: Discussionsupporting

confidence: 52%

“…In preconstricted adrenal cortical arteries, Ang II has biphasic vascular effects (36,37). In picomolar concentrations, Ang II causes vasorelaxation through activation of endothelial AT2 receptors and release of NO (36).…”

Section: Discussionmentioning

confidence: 99%

“…LC-MS and LC-MS/MS were performed using a modification of a previously described method (37,40). LC-MS/MS was used to identify the peptides, and LC-MS was used to quantify the Ang peptides.…”

Section: Lc-ms Analysismentioning

confidence: 99%

“…Isolated adrenal arterial segments were threaded on 2 stainless steel wires (40 m in diameter) and mounted on a 4-chamber wire myograph (model 610M; Danish Myo Technology) in physiological saline solution containing 119mM NaCl, 4.7mM KCl, 2.5mM CaCl 2 , 1.17mM MgSO 4 , 24mM NaHCO 3 , 1.18mM KH 2 PO 4 , 26M EDTA, and 5.5mM glucose, bubbled with 95% O 2 -5% CO 2 , at 37°C for 30 minutes, as previously described (37). Arteries were gradually stretched to a resting tension of 1mN and stimulated with KCl (60mM) plus U-46619 (100nM) 3 times for 10 minutes at 10-minute intervals to determine the maximal contraction.…”

Section: Vascular Reactivitymentioning

confidence: 99%

“…This primary vasodilation in adrenal arteries is unique to the adrenal circulation and has potentially important implications in the regulation of adrenal blood flow and steroidogenesis after stimulation of Ang II. Our initial studies demonstrated that this Ang II dilation response is mediated by activation of endothelial cell AT2 receptors and subsequent nitric oxide (NO) production (36), with Ang (1-7) having an insignificant role in this dilation response (37). With growing evidence of the importance of Ang metabolites, we examined a potential role of other Ang II metabolites (eg, Ang III and Ang IV) in the dilation response to Ang II in adrenal arteries.…”

mentioning

confidence: 99%

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Endothelial Metabolism of Angiotensin II to Angiotensin III, not Angiotensin (1–7), Augments the Vasorelaxation Response in Adrenal Cortical Arteries

Kopf

Campbell

2013

Endocrinology

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Hyperaldosteronism is linked to the development and progression of several different cardiovascular diseases. Angiotensin (Ang) II increases aldosterone secretion and adrenal blood flow. Ang II peptide fragments are produced by various peptidases, and these Angs have diverse and vital physiologic roles. Due to the uncharacteristic vasorelaxation of adrenal arteries by Ang II, we tested the hypothesis that Ang II metabolism contributes to its relaxant activity in adrenal arteries. Metabolism of Angs by bovine adrenal cortical arteries and isolated bovine adrenal vascular cells was measured by liquid chromatography-mass spectrometry. The primary Ang metabolites of adrenal arteries are Ang III and Ang (1-7), with Ang IV produced to a lesser extent. Bovine microvascular endothelial cells produced a similar metabolic profile to adrenal arteries, whereas bovine adrenal artery smooth muscle cells exhibited less metabolism. In preconstricted adrenal arteries, Ang II caused relaxation in picomolar concentrations and constrictions at 10nM. Ang-converting enzyme 2 inhibition augmented this relaxation response, whereas aminopeptidase inhibition did not. Ang III was equipotent to Ang II in relaxing adrenal arteries. Ang IV did not cause relaxation. Nitric oxide synthase inhibition enhanced Ang II-induced constriction of adrenal arteries. Aminopeptidase inhibition increased the concentration range for Ang II-induced constriction of adrenal arteries. Ang III and Ang IV did not change the basal tone but caused constriction of adrenal arteries with nitric oxide synthase inhibition. These data indicate that Ang II metabolism modulates the vascular effects of Ang II in the adrenal vasculature.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Lc-ms Analysismentioning

confidence: 99%

Section: Vascular Reactivitymentioning

confidence: 99%

mentioning

confidence: 99%

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Endothelial Metabolism of Angiotensin II to Angiotensin III, not Angiotensin (1–7), Augments the Vasorelaxation Response in Adrenal Cortical Arteries

Kopf

Campbell

2013

Endocrinology

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Impurity identification and determination for the peptide hormone angiotensin I by liquid chromatography–high-resolution tandem mass spectrometry and the metrological impact on value assignments by amino acid analysis

et al. 2013

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It is common practice to quantify the mass concentration of a peptide solution through quantitative determination of selected chemically stable amino acids produced following complete hydrolysis of the parent peptide. This is because there is generally an insufficient quantity of material available to allow for the obvious alternative of a direct purity analysis characterization of the parent peptide, and the subsequent constitution of a calibration solution. However, selected accurately characterized pure peptide reference materials are required to establish reference points for the dissemination of metrologically traceable measurements and to develop reference measurement systems for laboratory medicine. In principle, purity assignment of a peptide can be performed by using the so-called mass balance approach, by employing a range of analytical techniques to obtain an estimate of the mass fraction content of all impurities present in the intact peptide, and by utilizing the difference from the theoretical limit value to assign the mass fraction content of the main peptide. Liquid chromatography-high-resolution tandem mass spectrometry (LC-hrMS/MS) is a key technique for the detection, identification, and determination of structurally related impurities present in a peptide material, and experiments characterizing the model peptide hormone angiotensin I (ANG I) are described in the present work. Degradation products that were generated from ANG I after storage at elevated temperatures were screened. The formation of peptide fragments such as ANG II or ANG III was determined by comparison of measured mass values with calculated mass values. The use of a data-dependent acquisition technique enabled the detection and structural characterization of ANG II and other peptide fragments as major impurities in the same LC-hrMS/MS analysis run. Subsequent quantification using external calibration allowed the mass fraction of the major impurities in a candidate reference material to be estimated as 10.4 mg/g. Failure to correct for these impurities would lead to a 1% error in the determination of the concentration of the peptide in solution by amino acid analysis techniques.

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Detecting low-abundance vasoactive peptides in plasma: Progress toward absolute quantitation using nano liquid chromatography–mass spectrometry

Lortie

Bark

Blantz

et al. 2009

Analytical Biochemistry

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Profiling changes in the concentration of functionally related peptide hormones is critical to understanding the etiology of many diseases and therapies. We present novel data utilizing nano LC-MS to simultaneously measure a select group of vasoactive peptides (angiotensin, bradykinin and related hormones) in 50 μl plasma samples enabling repeated sampling in rodent models. By chromatographically resolving target peptides and using “multiple reaction monitoring” to enhance MS sensitivity, linear responses down to 10−17 mol were achieved. Purification of plasma peptides by either methanol precipitation or offline HPLC fractionation enabled the detection of endogenous peptides and revealed approaches for enhancing recovery. As proof of principle, seven vasoactive peptides were profiled before, during and after acute angiotensin converting enzyme (ACE) inhibition in an anesthetized rat. Of note was an apparent 10 fold increase in vasodilatory bradykinin that reversed after drug infusion but relatively minor changes in angiotensin II levels. Targeted MS analysis used to profile functionally related peptides or other analytes will greatly enhance our ability to define the sequence of events regulating complex and dynamic physiological processes.

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Angiotensin II Relaxations of Bovine Adrenal Cortical Arteries

Cited by 13 publications

References 31 publications

Endothelial Metabolism of Angiotensin II to Angiotensin III, not Angiotensin (1–7), Augments the Vasorelaxation Response in Adrenal Cortical Arteries

Endothelial Metabolism of Angiotensin II to Angiotensin III, not Angiotensin (1–7), Augments the Vasorelaxation Response in Adrenal Cortical Arteries

Impurity identification and determination for the peptide hormone angiotensin I by liquid chromatography–high-resolution tandem mass spectrometry and the metrological impact on value assignments by amino acid analysis

Detecting low-abundance vasoactive peptides in plasma: Progress toward absolute quantitation using nano liquid chromatography–mass spectrometry

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