Trial reportCardiovascular research2022
Neuronal nitric oxide synthase regulates regional brain perfusion in healthy humans.
Trial report in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Therapeutic potential of nitric oxide and its donors in hemorrhagic and ischemic stroke: a systematic review.Medical gas research · 2026Pooled it
- The Effect of a Neuronal Nitric Oxide Synthase Inhibitor on Neurovascular Regulation in Humans.Circulation research · 2022Trial
- Substance P regulates Tacr1 neurons, which control nitric oxide-mediated neurovascular coupling in the mouse cortex.Science advances · 2026Article
- Characterization of blood-brain barrier L-arginine uptake using in situ brain perfusions in a female mouse model.Fluids and barriers of the CNS · 2026Article
- Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations.International journal of molecular sciences · 2026Review
- The Emerging Role of Endothelial Ion Channels in the Control of Human Microcirculation.International journal of molecular sciences · 2026Review
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
- Compensatory retinal blood flow enhancement in cognitively normal ApoE ε4 carriers.Scientific reports · 2025Article
- Blockade of AGeroScience · 2025Article
- Acoustic therapy for allergic rhinitis and chronic rhinosinusitis: modulating microbiome, immunity and well-being.Frontiers in allergy · 2025Review
- Transient Receptor Potential Ankyrin 1 (TRPA1) Mediates Hydrogen Sulfide-induced CaCurrent neuropharmacology · 2025Article
- Rejuvenating the failing heart: multidimensional insights into young blood-mediated anti-aging pathways.Frontiers in endocrinology · 2025Review
- The Neural Palette of Heme: Altered Heme Homeostasis Underlies Defective Neurotransmission, Increased Oxidative Stress, and Disease Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- Dystroglycan-HSPG interactions provide synaptic plasticity and specificity.Glycobiology · 2024Review
- The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow.International journal of molecular sciences · 2024Review
- Association between intensity of physical activity and cognitive function in hypertensive patients: a case-control study.Scientific reports · 2024Article
- Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.Biomedicines · 2024Review
- Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2023Review
- Reduced basal macrovascular and microvascular cerebral blood flow in young adults with metabolic syndrome: potential mechanisms.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- The Acute Effects and Mechanism of Ketamine on Nicotine-Induced Neurogenic Relaxation of the Corpus Cavernosum in Mice.International journal of molecular sciences · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
aimsNeuronal nitric oxide synthase (nNOS) is highly expressed within the cardiovascular and nervous systems. Studies in genetically modified mice suggest roles in brain blood flow regulation while dysfunctional nNOS signalling is implicated in cerebrovascular ischaemia and migraine. Previous human studies have investigated the effects of non-selective NOS inhibition but there has been no direct investigation of the role of nNOS in human cerebrovascular regulation. We hypothesized that inhibition of the tonic effects of nNOS would result in global or localized changes in cerebral blood flow (CBF), as well as changes in functional brain connectivity. METHODS AND
resultsWe investigated the acute effects of a selective nNOS inhibitor, S-methyl-L-thiocitrulline (SMTC), on CBF and brain functional connectivity in healthy human volunteers (n = 19). We performed a randomized, placebo-controlled, crossover study with either intravenous SMTC or placebo, using magnetic resonance imaging protocols with arterial spin labelling and functional resting state neuroimaging. SMTC infusion induced an ∼4% decrease in resting global CBF [-2.3 (-0.3, -4.2) mL/100g/min, mean (95% confidence interval, CI), P = 0.02]. In a whole-brain voxel-wise factorial-design comparison of CBF maps, we identified a localized decrease in regional blood flow in the right hippocampus and parahippocampal gyrus following SMTC vs. placebo (2921 voxels; T = 7.0; x = 36; y = -32; z = -12; P < 0.001). This was accompanied by a decrease in functional connectivity to the left superior parietal lobule vs. placebo (484 voxels; T = 5.02; x = -14; y = -56; z = 74; P = 0.009). These analyses adjusted for the modest changes in mean arterial blood pressure induced by SMTC as compared to placebo [+8.7 mmHg (+1.8, +15.6), mean (95% CI), P = 0.009].
conclusionsThese data suggest a fundamental physiological role of nNOS in regulating regional CBF and functional connectivity in the human hippocampus. Our findings have relevance to the role of nNOS in the regulation of cerebral perfusion in health and disease.
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.