ArticleThe Journal of clinical investigation2021
Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- [Efficacy of β-Blockers in Older Adults With Hypertension Combined With Vascular Dementia].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Trial
- Endothelial Piezo1 Hyperactivity Drives Neurovascular Dysfunction in Hypertension.Circulation research · 2026Article
- Tau protein differentially affects Piezo1 and Kir2.1 channels in brain capillary endothelial cells.Biophysical journal · 2026Article
- Emerging roles for endothelial mineralocorticoid receptor in disease pathogenesis: potential new indications for mineralocorticoid receptor antagonism.Current opinion in physiology · 2026Article
- The stroke risk gene Foxf2 maintains brain endothelial cell function via Tie2 signaling.Nature neuroscience · 2026Article
- Diabetes and its complications: molecular mechanisms, prevention and treatment.Signal transduction and targeted therapy · 2026Review
- Brain Capillary Ion Channels: Physiology and Channelopathies.Physiology (Bethesda, Md.) · 2026Review
- Article
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- Examining the therapeutic potential and side effects of calcium channel blockers in mortality and morbidity of patients with stroke: A systematic review of pre-clinical and clinical studies.IBRO neuroscience reports · 2025Review
- Blood pressure and the brain: the conundrum of hypertension and dementia.Cardiovascular research · 2025Review
- Combining In Vivo Two-Photon and Laser Speckle Microscopy With the Ex Vivo Capillary-Parenchymal Arteriole Preparation as a Novel Approach to Study Neurovascular Coupling.Microcirculation (New York, N.Y. : 1994) · 2025Article
- CaInflammation and regeneration · 2024Review
- Ebbs and tides of endothelial KAmerican journal of physiology. Heart and circulatory physiology · 2024Article
- Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow.Nature communications · 2024Article
- Pathophysiology of cerebral small vessel disease: a journey through recent discoveries.The Journal of clinical investigation · 2024Review
- Assessment of Small Vessel Function Using 7T MRI in Patients With Sporadic Cerebral Small Vessel Disease: The ZOOM@SVDs Study.Neurology · 2024Observational
- Mechanosensing by Vascular Endothelium.Annual review of physiology · 2024Review
- Basic Mechanisms of Brain Injury and Cognitive Decline in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Mechanosensory entities and functionality of endothelial cells.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
- Commented on by
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.1. Despite similar efficacy in reducing blood pressure, amlodipine, a voltage-dependent calcium-channel blocker, prevented hypertension-related damage to functional hyperemia whereas losartan, an angiotensin II type 1 receptor blocker, did not. We attribute this drug class effect to losartan-induced aldosterone breakthrough, a phenomenon triggered by pharmacological interruption of the renin-angiotensin pathway leading to elevated plasma aldosterone levels. This hypothesis is supported by the finding that combining losartan with the aldosterone receptor antagonist eplerenone prevented the hypertension-related decline in functional hyperemia. Collectively, these data suggest Kir2.1 as a possible therapeutic target in vascular dementia and indicate that concurrent mineralocorticoid aldosterone receptor blockade may aid in protecting against late-life cognitive decline in hypertensive patients treated with angiotensin II type 1 receptor blockers.
Indexed as
Identifiers
What OpenQuestion holds
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.