Parameters of Blood Flow in Great Arteries in Hypertensive ISIAH Rats with Stress-Dependent Arterial Hypertension

Seryapina, A. A.; Shevelev, Oleg B.; Мошкин, М. П.; Al, Markel'

doi:10.1007/s10517-016-3440-0

Cited by 4 publications

(5 citation statements)

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“…The reduced level of eNOS and NO production in the renal medulla is associated with a reduction in medullary blood flow and have considerable importance in sodium and water homeostasis and the long-term control of arterial pressure [27–29]. Recently, the reduced renal blood flow measured by magnetic resonance angiography was reported in ISIAH rats as compared to normotensive Wistar rats [30]. So, the reduced transcription of the Nos3 in the renal medulla of ISIAH rats may be considered as a key feature possibly leading to the medullary blood flow reduction.…”

Section: Discussionmentioning

confidence: 99%

The gene-expression profile of renal medulla in ISIAH rats with inherited stress-induced arterial hypertension

et al. 2016

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BackgroundThe changes in the renal function leading to a reduction of medullary blood flow can have a great impact on sodium and water homeostasis and on the long-term control of arterial blood pressure. The RNA-Seq approach was used for transcriptome profiling of the renal medulla from hypertensive ISIAH and normotensive WAG rats to uncover the genetic basis of the changes underlying the renal medulla function in the ISIAH rats being a model of the stress-sensitive arterial hypertension and to reveal the genes which possibly may contribute to the alterations in medullary blood flow.ResultsMultiple DEGs specifying the function of renal medulla in ISIAH rats were revealed. The group of DEGs described by Gene Ontology term ‘oxidation reduction’ was the most significantly enriched one. The other groups of DEGs related to response to external stimulus, response to hormone (endogenous) stimulus, response to stress, and homeostatic process provide the molecular basis for integrated responses to homeostasis disturbances in the renal medulla of the ISIAH rats. Several DEGs, which may modulate the renal medulla blood flow, were detected. The reduced transcription of Nos3 pointed to the possible reduction of the blood flow in the renal medulla of ISIAH rats.ConclusionsThe generated data may be useful for comparison with those from different models of hypertension and for identifying the common molecular determinants contributing to disease manifestation, which may be potentially used as new pharmacological targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0462-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The gene-expression profile of renal medulla in ISIAH rats with inherited stress-induced arterial hypertension

et al. 2016

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“…Via blood sampling at short intervals and LC−MS analysis, it was found 3 min postinjection was sufficient for the SIL-mAb to be distributed homogenously in blood (Figure S3), consistent with the high cardiac output of rodents. 16,28 To ensure even distribution of SIL-mAb in circulation while minimizing its distribution into tissue (c.f. Figure 1b and Figure S3), perfusion was started 3 min after injection of SIL-mAb.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Then, an incision was made to the animal’s inferior vena cava to create an outlet. Heparinized saline was used to simulate physiological condition …”

Section: Methodsmentioning

confidence: 99%

“…Heparinized saline was used to simulate physiological condition. 16 To identify the optimal perfusion conditions, animals (n = 3 per group) were injected with 10 mg/kg of nonlabeled mAb AB095, and after 5 h, SIL-AB095 at 2 mg/kg. After 3 min, the animals were perfused using different volumes of saline containing 5 U/mL heparin (0.5−10 times of blood volumes).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Toward Accurate and Robust Liquid Chromatography–Mass Spectrometry-Based Quantification of Antibody Biotherapeutics in Tissues

Zhang

et al. 2020

Anal. Chem.

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Liquid chromatography–mass spectrometry (LC–MS) affords a highly promising solution for absolute quantification of biotherapeutics/targets in tissues, which is critical for drug development. Nonetheless, accurate/robust tissue quantification remains challenging largely owing to the lack of optimal approaches to address the following fundamental prerequisites: (i) efficient removal of residual blood without losing tissue-associated biotherapeutics; (ii) an optimal method to exhaustively/quantitatively recover target proteins from tissues; and (iii) an appropriate strategy to prepare calibration/quality-control samples to ensure accurate tissue analysis. Here, we devised novel analytical procedures enabling extensive and systematic investigation of the above issues and thereby development of optimal strategies for accurate tissue analysis. Key discoveries include: first, using a novel procedure of sequential administration of nonlabeled and then stable-isotope-labeled monoclonal antibody (mAb); it was determined that perfusion with three blood volumes of heparinized saline is optimal, achieving efficient blood removal (95–99%) and low quantitative bias (0.5–13%); second, a reference sample set established by mass-balanced, exhaustive extraction, permitted accurate measurement of absolute protein recovery from tissues of dosed animals; with this method, we found mAb biotherapeutics present in free-(49.3–75.4%) and bound-forms (24.6–50.7%) in tissues, even without a target; therefore, a denaturing detergent buffer is necessary for exhaustive extraction (recovery>90%); third, overnight-incubation of calibration samples after spiking mAb to tissue was found to improve quantitative accuracy, especially for nondenaturing buffer extraction. These investigations established the critical parameters and optimal protocols that can be universally applied to achieve accurate and robust quantification of biotherapeutics/targets in tissues. As a proof of concept, we conducted the first-ever extensive pharmacokinetics measurement of mAb in major tissues with a LC–MS-based method, where interesting features of mAb tissue disposition were observed.

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“…A peristaltic pump (1) set at a flow rate of 10 mL min −1 functioned as an artificial heart [38], and a PTFE tube acted as an artificial vein. Fresh anticoagulated pig blood (8 g) was placed in a matrix reservoir (2) and the temperature was controlled at 37 °C in a water bath.…”

Section: Simulation Of In Vivo Spme Samplingmentioning

confidence: 99%

Matrix compatibility of typical sol–gel solid-phase microextraction coatings in undiluted plasma and whole blood for the analysis of phthalic acid esters

Zhang

Chu

et al. 2022

Anal Bioanal Chem

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Sol-gel materials have been widely used for solid-phase microextraction (SPME) coatings due to their outstanding performance; in contrast, sol-gel SPME coatings have seldom been used for in vivo sampling. The main reason is that their matrix compatibility is unclear. In order to promote the application of this type of coating and accelerate the development of in vivo SPME, in this study, the matrix compatibility of several typical sol-gel coatings was assessed in plasma and whole blood using phthalic acid esters as analytes. The service life of five kinds of sol-gel coatings was among 20-35 times in undiluted plasma, while it was 27 times for a homemade commercial polydimethylsiloxane coating, which indicates good matrix compatibility of sol-gel coatings in untreated plasma. The sol-gel hydroxy-terminated silicone oil/methacrylic acid fiber achieved the highest extraction ability among all of the fibers, and it was tested in pig whole blood. It could be continuously used for at least 22 times, demonstrating good potential for in vivo sampling. Subsequently, a direct-immersion SPME/gas chromatography-flame ionization detection method was established for the determination of 5 phthalic acid esters in blood. Compared with other methods reported in the literature, this method is rapid, simple, sensitive, and accurate, and does not need expensive instruments or tedious procedures. A simulation system of animal blood circulation was constructed to verify the practicability of sol-gel SPME coatings in animal vein sampling. The result illustrated the feasibility of that coating for in vivo blood sampling, but a more accurate quantification calibration approach needs to be explored.

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Parameters of Blood Flow in Great Arteries in Hypertensive ISIAH Rats with Stress-Dependent Arterial Hypertension

Cited by 4 publications

References 10 publications

The gene-expression profile of renal medulla in ISIAH rats with inherited stress-induced arterial hypertension

The gene-expression profile of renal medulla in ISIAH rats with inherited stress-induced arterial hypertension

Toward Accurate and Robust Liquid Chromatography–Mass Spectrometry-Based Quantification of Antibody Biotherapeutics in Tissues

Matrix compatibility of typical sol–gel solid-phase microextraction coatings in undiluted plasma and whole blood for the analysis of phthalic acid esters

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