ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2020
Aging Alters Cerebrovascular Endothelial GPCR and K+ Channel Function: Divergent Role of Biological Sex.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Estrogen Enhances SK Channel Activity to Limit Hippocampal Arteriole Constriction.Circulation research · 2025Article
- Age-Related Choroidal Involution Is Associated with the Senescence of Endothelial Progenitor Cells in the Choroid.Biomedicines · 2024Article
- Impairment of microvascular endothelial Kir2.1 channels contributes to endothelial dysfunction in human hypertension.American journal of physiology. Heart and circulatory physiology · 2024Article
- Advancements in the study of inward rectifying potassium channels on vascular cells.Channels (Austin, Tex.) · 2023Review
- Cracking the Endothelial Calcium (CaInternational journal of molecular sciences · 2023Review
- Impact of aging on vascular ion channels: perspectives and knowledge gaps across major organ systems.American journal of physiology. Heart and circulatory physiology · 2023Review
- Endothelial KAmerican journal of physiology. Heart and circulatory physiology · 2023Article
- Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer's Disease.Biomedicines · 2022Article
- Alzheimer's disease and cerebrovascular pathology alter inward rectifier potassium (KBritish journal of pharmacology · 2022Article
- Isolation and Functional Analysis of Arteriolar Endothelium of Mouse Brain Parenchyma.Journal of visualized experiments : JoVE · 2022Article
- Biological determinants impact the neurovascular toxicity of nicotine and tobacco smoke: A pharmacokinetic and pharmacodynamics perspective.Neurotoxicology · 2022Review
- Vascular calcium signalling and ageing.The Journal of physiology · 2021Review
- Sex differences in the blood-brain barrier and neurodegenerative diseases.APL bioengineering · 2021Review
- Aging-Related Structural and Functional Changes in Cerebral Arteries: Caloric Restriction (CR) Intervention.Journal of vascular medicine & surgery · 2021Article
- Methyl-Beta-Cyclodextrin Restores KJournal of Alzheimer's disease reports · 2021Article
- Development of Alzheimer's Disease Progressively Alters Sex-Dependent KCa and Sex-Independent KIR Channel Function in Cerebrovascular Endothelium.Journal of Alzheimer's disease : JAD · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Age-related dementia entails impaired blood flow to and throughout the brain due, in part, to reduced endothelial nitric oxide signaling. However, it is unknown whether sex affects cerebrovascular Gq-protein-coupled receptors (GPCRs) and K+ channels underlying endothelium-derived hyperpolarization (EDH) during progressive aging. Thus, we simultaneously evaluated intracellular Ca2+ ([Ca2+]i) and membrane potential (Vm) of intact endothelial tubes freshly isolated from posterior cerebral arteries of young (4-6 mo), middle-aged (12-16 mo), and old (24-28 mo) male and female C57BL/6 mice. Purinergic receptor function (vs. muscarinic) was dominant and enhanced for [Ca2+]i increases in old females versus old males. However, Ca2+-sensitive K+ channel function as defined by NS309-evoked Vm hyperpolarization was mildly impaired in females versus males during old age. This sex-based contrast in declined function of GPCRs and K+ channels to produce EDH may support a greater ability for physiological endothelial GPCR function to maintain optimal cerebral blood flow in females versus males during old age. As reflective of the pattern of cerebral blood flow decline in human subjects, inward-rectifying K+ (KIR) channel function decreased with progressive age regardless of sex. Combined age-related analyses masked male versus female aging and, contrary to expectation, hydrogen peroxide played a minimal role. Altogether, we conclude a sex-based divergence in cerebrovascular endothelial GPCR and K+ channel function while highlighting a previously unidentified form of age-related endothelial dysfunction as reduced KIR channel function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.