Anandamide Inhibits Endothelin-1 Production by Human Cultured Endothelial Cells: A New Vascular Action of This Endocannabinoid

Ronco, Ana María; Llanos, Miguel; Tamayo, Daniela; Hirsch, Sandra

doi:10.1159/000097072

Cited by 18 publications

(17 citation statements)

References 52 publications

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“…As stated previously, it has been shown that activation of cannabinoid CB 1 receptors leads to vasorelaxation and a decrease in vascular resistance . This vasorelaxation seems to be mediated via the nitric oxide as well as the endothelin system, both of which are known to also play an important role in the regulation of vascular tone in the eye . To what extend the latter findings can be translated to the ocular vasculature needs to be further investigated.…”

Section: Discussionmentioning

confidence: 85%

The Effect of Orally Administered Dronabinol on Optic Nerve Head Blood Flow in Healthy Subjects—A Randomized Clinical Trial

Hommer

Kallab

Szegedi

et al. 2020

Clin Pharma and Therapeutics

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It has been hypothesized that besides its intraocular pressure (IOP) lowering potential, tetrahydrocannabinol (THC) may also improve ocular hemodynamics. The aim of the present study was to investigate whether single oral administration of dronabinol, a synthetic THC, alters optic nerve head blood flow (ONHBF) and its regulation in healthy subjects. The study was carried out in a randomized, placebo‐controlled, double‐masked, two‐way crossover design in 24 healthy subjects. For each study participant, 2 study days were scheduled, on which they either received capsules containing 5 mg dronabinol or placebo. ONHBF was measured with laser Doppler flowmetry at rest and while the study participants performed isometric exercise for 6 minutes to increase mean arterial blood pressure (MAP). This was repeated 1 hour after drug intake. Ocular perfusion pressure (OPP) was calculated as 2/3MAP–IOP. Dronabinol was well tolerated and no cannabinoid‐related psychoactive effects were reported. Neither administration of dronabinol nor placebo had an effect on IOP, MAP, or OPP. In contrast, dronabinol significantly increased ONHBF at rest by 9.5 ± 8.1%, whereas placebo did not show a change in ONHBF (0.3 ± 7.4% vs. baseline, P < 0.001 between study days). Dronabinol did not alter the autoregulatory response of ONHBF to isometric exercise. In conclusion, the present data indicate that low‐dose dronabinol increases ONHBF in healthy subjects without affecting IOP, OPP, or inducing psychoactive side effects. In addition, dronabinol does not alter the autoregulatory response of ONHBF to an experimental increase in OPP. Further studies are needed to investigate whether this effect can also be observed in patients with glaucoma.

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Section: Discussionmentioning

confidence: 85%

The Effect of Orally Administered Dronabinol on Optic Nerve Head Blood Flow in Healthy Subjects—A Randomized Clinical Trial

Hommer

Kallab

Szegedi

et al. 2020

Clin Pharma and Therapeutics

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“…1) The activation of presynaptic CB1R is known to reduce neurotransmitter release and excitotoxicity in postsynaptic neurons (Marsicano et al,2003). 2) CB1R is involved in the regulation of vasodilation, both directly through vascular CB1R and indirectly through the inhibition of the vasoconstrictor endothelin‐1 (Ronco et al,2007). 3) CB1R regulates the release of proinflammatory factors such as nitric oxide (NO), IL‐1β, IL‐6, and TNF‐α (Fernandez‐Lopez et al,2006; Panikashvili et al,2006).…”

Section: Discussionmentioning

confidence: 99%

Immunoregulation of experimental autoimmune encephalomyelitis by the selective CB1 receptor antagonist

Lou

Zhao

Xiao

2011

J of Neuroscience Research

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During immune-mediated demyelinating lesions, the endocannabinoid system is involved in the pathogenesis of both neuroinflammation and neurodegeneration through different mechanisms. Here we explored the cellular distribution of the CB1 receptor (CB1R) in the central nervous system (CNS) and detected the level of CB1R expression during experimental autoimmune encephalomyelitis (EAE) by RT-qPCR, Western blotting, and immunostaining. Expression of CB1R was observed in neurons and microglia/macrophages but was barely detected in astrocytes. During EAE, the expression of CB1R in spinal cords was reduced at days 9, 17, and 28 postimmunization (p.i.), but the level of CB1R expression in spleens did not show a significant difference compared with complete Freund's adjuvant (CFA)-immunized mice. A selective CB1R antagonist (SR141716A) increased EAE clinical score, accompanied by weight loss. Unexpectedly, SR141716A inhibited the expression of CB1R but increased the expression of CB2R in brains, spinal cords, and spleens simultaneously. The administration of SR141716A increased interferon-γ, interleukin-17 (IL-17), and inflammatory cytokines such as IL-1β, IL-6, and tumor necrosis factor-α in brains and/or spinal cords. A similar increase was observed in spontaneous and specific antigen-stimulated splenic mononuclear cells compared with vehicle controls. Interestingly, the expression of CX3CL1 was increased in brains and spinal cords but declined in spleens of EAE mice treated with SR141716A. These results indicate that manipulation of the CB1R may have therapeutic value in MS, but its complexity remains to be carefully considered and studied in further clinical application.

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“…A cannabinoid derivative attenuated LPS-mediated microglial activation by inhibiting NF-jB signaling pathway (More et al 2013). Besides their anti-neuroinflammatory mechanisms, cannabinoids possess neuroprotective properties via diminishing excitotoxicity in postsynaptic neurons (Marsicano et al 2003), enhancing vasodilation through CB 1 in vascular smooth muscle, and the inhibition of endothelin-1 (Ronco et al 2007).…”

Section: Cannabinoidsmentioning

confidence: 99%

Involvement of inflammation in Alzheimer’s disease pathogenesis and therapeutic potential of anti-inflammatory agents

et al. 2015

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Alzheimer's disease (AD) is the most common form of dementia. It is characterized by beta-amyloid (Aβ) peptide fibrils, which are extracellular depositions of a specific protein, and is accompanied by extensive neuroinflammation. Various studies have demonstrated risk factors that can affect AD pathogenesis, and they include accumulation of Aβ, hyperphosphorylation of tau protein, and neuroinflammation. Among these detrimental factors, neuroinflammation has been highlighted by epidemiologic studies suggesting that use of anti-inflammatory drugs could significantly reduce the incidence of AD. Evidence suggests that astrocytes, microglia, and infiltrating immune cells from periphery might contribute to or modify the process of neuroinflammation and neurodegeneration in AD brains. In addition, recent data indicate that microRNAs may affect neuroinflammatory responses in the brain. This article focuses on supportive evidence that neuroinflammation plays a critical role in AD development. In addition, we depict putative therapeutic capacity of anti-inflammatory drugs for AD prevention or treatment. We also discuss pathogenic mechanisms by which astrocytes, microglia, T cells and microRNA participate in AD and the neuroprotective mechanisms of anti-inflammatory drugs.

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Anandamide Inhibits Endothelin-1 Production by Human Cultured Endothelial Cells: A New Vascular Action of This Endocannabinoid

Cited by 18 publications

References 52 publications

The Effect of Orally Administered Dronabinol on Optic Nerve Head Blood Flow in Healthy Subjects—A Randomized Clinical Trial

The Effect of Orally Administered Dronabinol on Optic Nerve Head Blood Flow in Healthy Subjects—A Randomized Clinical Trial

Immunoregulation of experimental autoimmune encephalomyelitis by the selective CB1 receptor antagonist

Involvement of inflammation in Alzheimer’s disease pathogenesis and therapeutic potential of anti-inflammatory agents

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