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Key Event: 2230

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased, afferent artery vasoconstriction

Short name

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Biological Context

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Level of Biological Organization
Tissue

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term
kidney

Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
vasoconstriction	kidney afferent arteriole smooth muscle cell	increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Activation of PKC leads to Kidney Failure	KeyEvent	Arthur Author (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
human	Homo sapiens	High	NCBI
mouse	Mus musculus	High	NCBI
mammals	mammals	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
All life stages

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

As blood travels from the aorta into the renal arteries, it divides into smaller vessels known as the afferent arteries, which are intricately involved in kidney-specific blood flow regulation. These arteries play an essential role in governing the amount of blood that enters the kidneys (Eaton, 2009). Further branching of the afferent arteries leads to the Bowman's capsule, specifically the glomerulus, where blood filtration occurs (Terasaki, 2020). This filtration process is essential for removing waste products and regulating electrolyte balance (Dalal, 2024).

The biological significance of afferent arteries extends beyond blood flow regulation. They actively influence vital physiological processes such as blood pressure and the glomerular filtration rate (GFR) (Dalal, 2023). By adjusting their diameter, these arteries modulate the pressure within the glomeruli, thus impacting the rate at which blood is filtered in the kidneys (Gohar, 2019).

Vasoconstriction, a phenomenon characterized by the narrowing of blood vessels, profoundly influencing vascular function (NIH, 2023). This physiological process, governed by small muscles within the vessel walls, is subject to various factors including medications, medical conditions, stress, and smoking (Cleveland Clinic Medical, 2024). Hormones such as angiotensin II, and norepinephrine intricately regulate vasoconstriction (Wilson, 1896).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Vasoconstriction of the afferent arteries, a crucial aspect of renal hemodynamics, can be indirectly assessed through the measurement of renal blood flow (RBF) or the glomerular filtration rate (GFR) (Feher, 2017).

Renal blood flow can be noninvasively evaluated using various techniques, including contrast-enhanced ultrasound, positron emission tomography (PET), magnetic resonance imaging (MRI), and computerized tomography (CT) (Thurman & Gueler, 2018). Traditional methods utilize radioisotopes or clearance methods with substances like para-aminohippurate (Moraitis, 2024). Enhanced vasoconstriction typically results in a decrease in RBF (Dalal, 2023).

Similarly, GFR, a key indicator of renal function, can be directly measured using exogenous filtration markers like inulin and iohexol, or indirectly estimated through endogenous markers such as serum creatinine and cystatin C (Thompson, 2022). Indirect measurement, often via urine sample collection over time, is more common due to its non-invasiveness. Radioisotope techniques are also available for GFR assessment (LaFrance, 1988). Increased vasoconstriction generally leads to a reduction in GFR (Dalal, 2023).

These methods collectively provide valuable insights into the impact of afferent artery vasoconstriction on renal function, aiding in the diagnosis and management of renal disorders.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Taxonomic Applicability: The key event applies to vertebrates. Afferent arterioles are a kidney specific biological structure, and therefore specific to vertebrates since kidneys are vertebrate specific.

Life Stage Applicability: The key event is not life stage specific. Vasoconstriction of the afferent arterioles can happen at any age; therefore, the KE is not life stage specific. Age may have an influence on the integrity of the arterioles however, the KE can occur regardless.

Sex Applicability: The key event is not sex specific. Afferent arterioles are not a sex specific biological structure in the kidneys. There is no significant influence on vasoconstriction reactivity to endothelin receptor activation between the sexes (Gohar, 2019).

References

List of the literature that was cited for this KE description. More help

Cleveland Clinic Medical. (2024). Vasoconstriction: What is it, symptoms, causes & treatment. Cleveland Clinic. https://my.clevelandclinic.org/health/symptoms/21697-vasoconstriction

Dalal, R., Bruss, Z.S, Sehdev, J.S. Physiology, Renal Blood Flow and Filtration. [Updated 2023 Jul 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482248/

Eaton, D. C., & Pooler, J. (2009). Vander’s Renal Physiology. McGraw-Hill Education.

Feher, J. J. (2017). Quantitative human physiology: An introduction. Academic Press.

Gohar, E. Y., Cook, A. K., Pollock, D. M., & Inscho, E. W. (2019). Afferent arteriole responsiveness to endothelin receptor activation: does sex matter?. Biology of sex differences, 10(1), 1. https://doi.org/10.1186/s13293-018-0218-2

LaFrance, N. D., Drew, H. H., & Walser, M. (1988). Radioisotopic measurement of glomerular filtration rate in severe chronic renal failure. Journal of nuclear medicine: official publication, Society of Nuclear Medicine, 29(12), 1927–1930.

Moraitis, A., Jentzen, W., Fragoso Costa, P., Kersting, D., Himmen, S., Coelho, M., Meckel, M., van Echteld, C. J. A., Fendler, W. P., Herrmann, K., & Sraieb, M. (2024). Safety and Efficacy of Para-Aminohippurate Coinfusion for Renal Protection During Peptide Receptor Radiotherapy in Patients with Neuroendocrine Tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 65(6), 931–937. https://doi.org/10.2967/jnumed.123.266619

NIH (2023). Vasoconstriction: MedlinePlus medical encyclopedia. MedlinePlus. https://medlineplus.gov/ency/article/002338.htm#:~:text=Vasoconstriction%20is%20the%20narrowing%20(constriction,%2C%20medicines%2C%20or%20psychological%20conditions

Terasaki, M., Brunson, J. C., & Sardi, J. (2020). Analysis of the three-dimensional structure of the kidney glomerulus capillary network. Scientific reports, 10(1), 20334. https://doi.org/10.1038/s41598-020-77211-x

Thompson, L. E., & Joy, M. S. (2022). Endogenous markers of kidney function and renal drug clearance processes of filtration, secretion, and reabsorption. Current opinion in toxicology, 31, 100344. https://doi.org/10.1016/j.cotox.2022.03.005

Thurman, J., & Gueler, F. (2018). Recent advances in renal imaging. F1000Research, 7, F1000 Faculty Rev-1867. https://doi.org/10.12688/f1000research.16188.1

Wilson S. K. (1986). The effects of angiotensin II and norepinephrine on afferent arterioles in the rat. Kidney international, 30(6), 895–905. https://doi.org/10.1038/ki.1986.270