Cannabinoid modulation of perivascular sympathetic and sensory neurotransmission.
Abstract
Cannabinoids are signalling molecules which elicit their vascular effects mainly via G protein-coupled CB(1) receptors and transient receptor potential (TRP) channels (chiefly vanilloid TRPV1 receptors). Cannabinoids can act at prejunctional CB(1) receptors to inhibit perivascular sympathetic neurotransmission. The effects of cannabinoids on perivascular capsaicin-sensitive sensory nerves are more complex. Certain cannabinoids can activate sensory nerves through actions on TRPV1 receptors and other TRP channels, which leads to sensory neurotransmitter release (mainly calcitonin gene-related peptide) and vasorelaxation. However, activation of TRP/TRPV1 channels can also lead to desensitization and loss of sensory nerve activity. Concentration and time of exposure may be critical in determining which of these opposite effects of cannabinoids prevails. In addition, there is evidence for the expression of CB(1) receptors on perivascular capsaicin-sensitive sensory nerves, coupled to inhibition of neurotransmitter release. There is evidence that the archetypal cannabinoid anandamide is released as a neurotransmitter in the central nervous system, and from sensory ganglia, but a release of cannabinoids from perivascular nerves has yet to be clearly demonstrated. Hence, with regard to perivascular nerves, cannabinoids appear to act principally as prejunctional modulators of neurotransmission. The diverse prejunctional effects of cannabinoids may be novel targets for therapies designed to treat vascular disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The endocannabinoid system is involved in neurovascular coordination.
“Investment of the sprouted fibers with CB1 receptors supports the suggestion that the endocannabinoid system is involved in this neurovascular coordination [43]”
From Endocannabinoid involvement in endometriosis. (2010) · cites this paper as [43]
Cited by
Sorted by citations
CB1 Cannabinoid Receptors and their Associated Proteins
Howlett, A. C., Blume, L. C., & Dalton, G. D. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710790980023 · Cited by 296 · see citing works
“The interest in metabolic syndrome led to the expansion of studies of CB1 receptors on vascular as well as cardiac tissue [28] [29,30].”
BackgroundWhy do cannabinoid receptors have more than one endogenous ligand?
Di Marzo, V., & De Petrocellis, L. (2012) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2011.0382 · Cited by 290 · see citing works
Adverse Effects of Cigarette and Noncigarette Smoke Exposure on the Autonomic Nervous System
Middlekauff, H. R., Park, J., & Moheimani, R. S. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.06.1201 · Cited by 240 · see citing works
Endocannabinoid signalling: has it got rhythm?
Vaughn, L. K., Denning, G., Stuhr, K. L., de Wit, H., Hill, M. N., & Hillard, C. J. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00790.x · Cited by 176 · see citing works
“In addition to very prominent expression within the brain, ECS has been identified in the spinal cord (Hohmann, 2002), sympathetic nervous system (Ralevic and Kendall, 2009), enteric nervous system (Massa and Monory, 2006), liver (Mallat and Lotersztajn, 2008), adipose tissue (Nogueiras et al.”
BackgroundEndocannabinoids in cerebrovascular regulation
Benyó, Z., Ruisanchez, É., Leszl-Ishiguro, M., Sándor, P., & Pacher, P. (2016) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00571.2015 · Cited by 87 · see citing works
Endocannabinoid involvement in endometriosis.
Dmitrieva, N., Nagabukuro, H., Resuehr, D., Zhang, G., McAllister, S. L., McGinty, K. A., Mackie, K., & Berkley, K. J. (2010) · Pain · doi:10.1016/j.pain.2010.08.037 · Cited by 64 · see citing works
“Investment of the sprouted fibers with CB1 receptors supports the suggestion that the endocannabinoid system is involved in this neurovascular coordination [43], which has implications for conditions other than endometriosis.”
BackgroundSympathetic and sensory-motor nerves in peripheral small arteries
Aalkjær, C., Nilsson, H., & Mey, J. G. R. D. (2020) · Physiological Reviews · doi:10.1152/physrev.00007.2020 · Cited by 62 · see citing works
Anandamide and its metabolites what are their roles in the kidney
Ritter, J. K. (2016) · Frontiers in Bioscience-Scholar · doi:10.2741/s461 · Cited by 44 · see citing works
Richards, J. R. (2020) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248420935743 · Cited by 39 · see citing works
“However, this response is not universal, as TRP-mediated vasoconstriction also may occur in coronary, cerebral, and peripheral arterial systems.(87,88) It is possible exogenous cannabinoids at supratherapeutic doses may cause acute coronary or cerebral vasoconstriction, leading to ACS and stroke.”
BackgroundOn the Sympathetic Innervation of the Human Greater Saphenous Vein: Relevance to Clinical Practice
Loesch, A., & Dashwood, M. R. (2009) · Current Vascular Pharmacology · doi:10.2174/157016109787354150 · Cited by 34 · see citing works
Cannabis in liver disorders: a friend or a foe?
Goyal, H., Rahman, M. R., Perisetti, A., Shah, N., & Chhabra, R. (2018) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000001256 · Cited by 33 · see citing works
Wang, H., Wang, D. H., & Galligan, J. J. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00235.2009 · Cited by 28 · see citing works
Henkin, R. I., Potolicchio, S. J., & Lucien Levy, C. (2013) · Brain Sciences · doi:10.3390/brainsci3041483 · Cited by 28 · see citing works
“Cannabinoids act at prejunctional CB1 receptors to inhibit sympathetic neurotransmission [408].”
BackgroundRole of Endocannabinoids and Cannabinoid-1 Receptors in Cerebrocortical Blood Flow Regulation
Iring, A., Ruisanchez, É., Leszl-Ishiguro, M., Horváth, B., Benkő, R., Lacza, Z., Járai, Z., Sándor, P., Marzo, V. D., Pacher, P., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053390 · Cited by 26 · see citing works
“For this purpose we applied a drug, AM-251, which acts both as an inverse agonist, thereby inhibiting the well-documented constitutive activity of CB1receptors [45,46], and also as an antagonist, thereby blocking the potential effects of resting EC release.”
InfluentialMarchetti, B., Bilel, S., Tirri, M., Arfè, R., Corli, G., Roda, E., Locatelli, C., Cavarretta, E., De‐Giorgio, F., & Marti, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021631 · Cited by 18 · see citing works
“Moreover, the activation of the CB1 receptor in the perivascular sympathetic nerve leads to neurotransmitters modulation, such as γ-aminobutyric acid or glutamate and other monoamines, which causes a vasoconstrictor effect and hypertension [35,77,78].”
BackgroundModulation of Noradrenergic Neurotransmission in Isolated Rat Radial Artery
Martı́nez, A. C., Pagán, R. M., Prieto, D., et al. (2009) · Journal of Pharmacological Sciences · doi:10.1254/jphs.09135fp · Cited by 18 · see citing works
López‐Gómez, L., Szymaszkiewicz, A., Zielińska, M., & Abalo, R. (2022) · Molecules · doi:10.3390/molecules27196773 · Cited by 16 · see citing works
Pintori, N., Serra, M. P., Carai, A., Lobina, C., Isola, R., Noli, R., Piras, G., Spano, E., Baumann, M. H., Quartu, M., et al. (2024) · Toxicology · doi:10.1016/j.tox.2024.153878 · Cited by 8 · see citing works
Marchetti, B., Bilel, S., Tirri, M., Corli, G., Roda, E., Locatelli, C., Cavarretta, E., De‐Giorgio, F., & Marti, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087515 · Cited by 8 · see citing works
“This evidence could suggest that hypertension induced by JWH-018 was probably caused by a peripheral action that involves calcium channel [92] during the first hour, while during the following hours of the experiment the central action on dorsal periaqueductal gray (dPAG) could prevail [93].”
BackgroundKansui, Y., Gotō, K., Ohtsubo, T., et al. (2012) · Hypertension Research · doi:10.1038/hr.2012.61 · Cited by 3 · see citing works
Endocannabinoids: the lipid effectors of metabolic regulation in health and disease
Jourdan, T., Degrace, P., González‐Mariscal, I., Szanda, G., & Tam, J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819404-1.00015-4 · Cited by 2 · see citing works
Fakhoury, B., Jahagirdar, V., Rama, K., Hudson, D., Wang, W., Díaz, L. A., & Arab, J. P. (2025) · Liver International · doi:10.1111/liv.70401 · Cited by 1 · see citing works
“Both AEA and 2-AG are key endocan-nabinoids that modulate CB1 and CB2, influencing sensory and autonomic signalling, energy homeostasis and immune responses [4, 6, 7].”
Central regulation of Blood Brain Barrier integrity during hyperalgesia
Campos, C. R. (2009) · UA Campus Repository (The University of Arizona)
Studies investigating the mechanisms of the cardioprotective effects of cannabidiol
Hepburn, C. Y. (2014) · Open Access Institutional Repository at Robert Gordon University (Robert Gordon University)
- Authors
- Ralevic, V., & Kendall, D.
- Affiliations
- University of Nottingham (GB)
- ORCID
- Ralevic, Vera
- Venue
- Current Vascular Pharmacology
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2009-01-01
- Volume
- 7
- Issue
- 1
- Pages
- 15-25
- ISSN
- 1570-1611 (ISSN-L)
- OpenAlex
- W2048924952
- Cited by
- 24
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2020: 3 · 2018: 1 · 2016: 2 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Vascular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Heart Foundation
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- cannabinoids, CB1 receptor, TRPV1 receptor, TRP channels, sensory nerves, calcitonin gene-related peptide, vasorelaxation, anandamide, vascular disease therapy
- MeSH terms
- Animals, Cannabinoids, Humans, Synaptic Transmission, Sympathetic Nervous System, Signal Transduction, Receptors, Cannabinoid, TRPV Cation Channels
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
