Angiotensin-2 Infusion induced Hypertension Modeling & Pharmacodynamics Service

Introduction

Hypertension, a pervasive global health challenge, significantly elevates the risk of severe cardiovascular and renal complications. Effective therapeutic development hinges on the availability of robust and physiologically relevant preclinical models that accurately mimic human disease conditions.

At Creative Biolabs, we are dedicated to advancing hypertension research by providing a comprehensive suite of well-established rodent models, enabling precise evaluation of novel antihypertensive agents and mechanistic insights.

Angiotensin-2 Infusion Induced Hypertension Model

The Angiotensin-2 (Ang II) infusion model offers a direct and highly reproducible method to induce chronic hypertension. This model precisely mimics the sustained activation of the renin-angiotensin system (RAS), a key driver in various forms of human hypertension, including essential and renovascular hypertension. By continuously delivering supraphysiological levels of Ang II, the model facilitates the study of its profound effects on blood pressure regulation, vascular function, and the development of critical end-organ damage, such as cardiac hypertrophy, renal fibrosis, and vascular remodeling. It is frequently referred to as an "Ang II slow-pressor model" due to its characteristic gradual and sustained elevation in blood pressure, mirroring clinical progression.

Ang II and its mechanisms to reduce baroreflex sensitivity. (OA Literature)Fig.1 Mechanisms of Ang II-induced hypertension.1

Model Construction Steps

The Ang II infusion model is typically established through the surgical implantation of osmotic mini-pumps in small animal models, most commonly mice or rats. These specialized pumps are designed to deliver Ang II at a constant, controlled rate over an extended period, usually spanning several weeks.

01Species and Strain Selection

Appropriate rodent species and specific strains are chosen based on research objectives and known sensitivities to Ang II.

02Ang II Dosage Determination

The precise Ang II infusion rate (e.g., 0.7-2.0 μg/kg/min for mice) is carefully titrated to achieve a consistent and desired level of hypertension.

03Osmotic Mini-Pump Preparation

Osmotic mini-pumps are loaded with the prepared Ang II solution according to guidelines, ensuring sterile conditions.

04Surgical Implantation

Under aseptic surgical conditions and appropriate anesthesia, the Ang II-filled osmotic mini-pump is subcutaneously implanted, typically in the dorsal region of the animal.

05Post-Operative Care

Animals receive diligent post-operative care, including analgesia and monitoring for recovery.

06Blood Pressure Monitoring

Blood pressure is routinely monitored throughout the infusion period using either non-invasive tail-cuff plethysmography or, for higher precision and continuous data, invasive telemetry via implanted catheters.

Strengths and Limitations

Strengths:

  • High Reproducibility: Consistently generates predictable and stable hypertension.
  • Translational Relevance: Closely mirrors Ang II-dependent human hypertension, including neurogenic, oxidative stress, and intracellular signaling components.
  • Robust End-Organ Damage: Reliably induces hallmark cardiac, renal, and vascular pathologies.
  • Controlled Stimulus: Allows for precise control over the hypertensive insult via Ang II dosage.

Limitations:

  • Surgical Requirement: Involves a minor surgical procedure for pump implantation.
  • Cost and Time Investment: Osmotic mini-pumps and Ang II peptide can represent a significant investment.
  • Systemic Effects: The supraphysiological Ang II levels can induce widespread systemic effects, requiring careful interpretation of results.

Evaluation Platform

Creative Biolabs' state-of-the-art evaluation platform integrates diverse techniques for comprehensive analysis:

  • Physiological Assessments: Cardiac function (e.g., echocardiography), renal function (e.g., serum creatinine, BUN, albuminuria), and vascular reactivity.
  • Biomarker Analysis: Inflammatory markers, oxidative stress indicators, and sympathetic nervous system activity.
  • Molecular & Cellular Insights: Analysis of crucial signaling molecules like Ras, MAP kinase, CYP450 activity, and intrarenal Ang II content.
  • Histopathological & Imaging: Detailed tissue analysis and advanced imaging techniques for structural changes.

Applications

  • Simulated Diseases: Effectively simulates various forms of hypertension, including RAS-mediated hypertension, essential hypertension, renovascular hypertension, and hypertension associated with metabolic syndrome.
  • Drug Evaluation: Ideal for assessing the antihypertensive efficacy of novel compounds, including direct RAS inhibitors (e.g., AT1 receptor blockers, ACE inhibitors, renin inhibitors), and agents targeting sympathetic activity, oxidative stress pathways, Ras/MAP kinase, and Cytochrome P450 metabolites.
  • Mechanistic Elucidation: Facilitates deep dives into the molecular and cellular mechanisms underlying Ang II-mediated hypertension, inflammation, fibrosis, and the interplay with endogenous RAS components.
  • Therapeutic Strategies: Supports the evaluation of monotherapies, combination therapies, and the impact of lifestyle interventions on blood pressure and end-organ protection.

Related Hypertension Models

Our Advantages

  • Customized Study Design: Protocols are meticulously tailored to align with your specific research objectives.
  • Precise Model Induction: We ensure consistent and reliable model establishment through expert surgical techniques.
  • Gold-Standard Monitoring: Utilize advanced blood pressure monitoring, including highly accurate telemetry.
  • Comprehensive Characterization: Access in-depth phenotypic, histopathological, and molecular analyses.
  • Insightful Data Interpretation: Receive clear, actionable insights from our seasoned scientists.

Work with Us

1
Inquiry Stage
  • Summarize the project requirements and fill in the information collection form.
  • Sign a CDA from both parties to further communicate information, such as targets.
  • Select an animal model, discuss experimental design, and determine assay parameters.
  • Project costing and project schedule forecasting.
2
Project Start
  • We provide a detailed project plan, including the required sample quantities, methods, and protocols.
  • Both parties confirm the project details and start the project.
  • Confirm the timeline of the project.
3
Project Progress
  • We provide periodic results and information on the animal's condition.
  • We will work together to make project adjustments as necessary.
4
Project Completion
  • We provide a comprehensive project report promptly.
  • We arrange transportation for the produced samples.
  • We provide a discussion of the project results and help to arrange the next steps.
5
After-Sales Support
  • Data storage and archiving.

Contact Us

Creative Biolabs is your dedicated partner in hypertension research, offering unparalleled scientific rigor and technical excellence. We provide comprehensive services from model establishment to data analysis. Contact us today to discuss how our expertise can accelerate your drug discovery and development efforts.

FAQs

  1. Q1: Why should I consider the Ang II infusion model over other hypertension models?

    A: The Ang II infusion model is highly relevant for hypertension research, directly targeting the RAS, a key human blood pressure driver. It offers controlled, reproducible blood pressure elevation, enabling precise mechanistic investigation and therapeutic efficacy assessment. Its consistent induction of end-organ damage is also invaluable for evaluating protective strategies.

  2. Q2: How is blood pressure accurately measured in animals subjected to Ang II infusion?

    A: Blood pressure monitoring can be performed via non-invasive tail-cuff plethysmography for routine measurements. For precise, continuous data in conscious animals, invasive telemetry with implanted catheters is the gold standard, providing real-time readings and minimizing stress-induced variability.

  3. Q3: Is this model suitable for long-term studies, or is it primarily for acute investigations?

    A: This model is highly versatile, suitable for both acute and chronic investigations. While initial blood pressure elevation occurs within days, sustained Ang II infusion over several weeks (typically 2-4 weeks or longer) enables progressive end-organ damage development, making it ideal for evaluating long-term therapeutic efficacy and disease progression.

  4. Q4: How does Creative Biolabs ensure the reproducibility and consistency of the Ang II infusion model?

    A: Creative Biolabs ensures reproducibility through stringent protocols and experienced scientific personnel. This involves precise Ang II dosage control, meticulous osmotic mini-pump implantation, standardized animal husbandry, and rigorous blood pressure monitoring. Our quality control and detailed data analysis further guarantee reliable, consistent outcomes.

  5. Q5: How do you handle data analysis and reporting for studies using this model?

    A: Our seasoned scientists provide expert data analysis and interpretation, transforming raw data into clear, insightful reports. We employ advanced statistical methods to ensure data integrity, offering comprehensive summaries, graphical representations, and detailed discussions of findings. Our goal is to empower your decision-making.

  6. Q6: Is it possible to evaluate combination therapies or lifestyle interventions using this model?

    A: Yes, the Ang II infusion model is exceptionally well-suited for evaluating combination therapies, where multiple antihypertensive agents are administered concurrently. It can also assess the impact of various lifestyle interventions, such as dietary modifications or exercise regimens, on the development and progression of Ang II-induced hypertension and associated pathologies.

Published Data

Change in MAP, SBP, DBP, heart rate, body temperature, and activity levels during Ang II infusion. (OA Literature)Fig.2 Establishment of the Ang II-induced hypertension model.2

ChAT protein decreases blood pressure in Ang II-induced hypertension. (OA Literature)Fig.3 ChAT administration decreases blood pressure.2

In a compelling study, researchers investigated the novel therapeutic potential of choline acetyltransferase (ChAT) in murine Ang II-induced hypertension. Their research demonstrated that systemic administration of recombinant ChAT significantly and dose-dependently reduced mean arterial pressure (MAP) in hypertensive mice. This blood pressure-lowering effect was shown to be nitric oxide-dependent, indicating a mechanism of endothelium-dependent vasodilation. Furthermore, PEGylated ChAT (PEG-ChAT) exhibited a longer-lasting antihypertensive effect, particularly when administered during the active cycle when blood pressure was highest. This work highlights the Ang II infusion model's utility in uncovering new therapeutic avenues and validating novel biological interventions for hypertension.

References

  1. de Queiroz, Thyago M et al. "Angiotensin-II-derived reactive oxygen species on baroreflex sensitivity during hypertension: new perspectives." Frontiers in physiology vol. 4 105. 13 May. 2013. Distributed under Open Access license CC BY 3.0, without modification. https://doi.org/10.3389/fphys.2013.00105
  2. Stiegler, Andrew et al. "Systemic administration of choline acetyltransferase decreases blood pressure in murine hypertension." Molecular medicine (Cambridge, Mass.) vol. 27,1 133. 21 Oct. 2021. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.1186/s10020-021-00380-6

For Research Use Only.


Related Services:
Renal Artery Stenosis induced Hypertension Model
5/6 Nephrectomy induced Hypertension Model
SHR Model
L-NAME induced Hypertension Model
Hypoxia induced Pulmonary Hypertension Model
hRN/hANG Transgentic Mouse Hypertension Model
Salt induced Hypertentison Model
Abdominal Aorta Constriction induced Hypertension Model
Monocrotaline induced Pulmonary Hypertension Model
DOCA-Salt induced Hypertension Model
Primate Hypertension Model
Online Inquiry
Name:
Phone:
*E-mail Address:
*Service & Products Interested:
Project Description: