Anandamide-Mediated CB<sub>1</sub>/CB<sub>2</sub>Cannabinoid Receptor-Independent Nitric Oxide Production in Rabbit Aortic Endothelial Cells

McCollum, LaTronya; Howlett, Allyn C.; Mukhopadhyay, Somnath

doi:10.1124/jpet.106.117549

Cited by 46 publications

(50 citation statements)

References 39 publications

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“…There are however, a number of potential targets that may be responsible. It has been reported that endogenous cannabinoids such as 2-AG and anandamide may induce vasodilation through a non-cannabinoid receptor (such as vanilloid receptor) present on endothelial cells (Golech et al, 2004, McCollum et al, 2007. It has been shown that cannabidiol, the nonpsychoactive constituent of cannabis, also reduced cerebral infarction due to increases in rCBF during ischemia, through activiation of the serotonergic 5-hydroxytryptamine 1A receptor (Mishima et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The hypothesis that modification of the endocannabinoid system could influence outcome following ischemia was based upon prior reports that this system can have direct effects on neuronal function and can also modify inflammatory responses (Baker et al, 2001, van der Stelt et al, 2001, Muthian et al, 2004, McCollum et al, 2007. Both of these actions could have significant impact on cerebral ischemia/reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

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Modulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Modulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury

et al. 2008

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“…In animal studies, there is a large evidence supporting a role for ECS in improving endothelial function and nitric oxide production 37 as well as THC has been shown to Endothelial dysfunction in erectile dysfunction A Aversa et al improve endothelium-dependent relaxation. [38][39][40] In addition, the EC anandamide, improves neurogenic relaxation of corpus cavernosum in diabetic rats. 41 On the contrary, occasional myocardial infarction after acute assumption of cannabis has been reported in humans.…”

Section: Endothelial Dysfunction In Erectile Dysfunction a Aversa Et Almentioning

confidence: 99%

Early endothelial dysfunction as a marker of vasculogenic erectile dysfunction in young habitual cannabis users

et al. 2008

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Aim of the study was to evaluate whether endothelial dysfunction is a marker of erectile dysfunction (ED) in recreational drug abuse. Sixty-four non-consecutive men complaining of ED from at least 3 months were included. All patients underwent detailed history about recreational drug abuse and were then submitted to dynamic penile duplex ultrasound (PDU). According to pharmaco-stimulated peak systolic velocity (PSV) cutoff at 35 cm s À1 , patients were divided into two groups: organic (O; n ¼ 30) and non-organic (NO; n ¼ 34) ED. All subjects and 7 healthy age-matched subjects as controls, underwent veno-occlusive plethysmography (VOP) for the evaluation of endothelium-dependent dilatation of brachial arteries. Blood pressure, total and free testosterone, prolactin, estradiol, low-density lipoprotein and high-density lipoprotein cholesterol were also evaluated; patients were classified with regard to insulin resistance through the HOMA-IR index. Cannabis smoking was more frequent in O-ED vs NO-ED (78% vs 3%, Po0.001) in the absence of any concomitant risk factor or comorbidity for ED. VOP studies revealed impaired endotheliumdependent vasodilatation in O-ED but not in NO-ED and controls (12±6 vs 32±4 and 34 ± 5 ml min À1 , respectively; P ¼ 0.003). Overall patients showed a direct relationship between HOMA-IR and PSV (r 2 ¼ 0.47, Po0.0001), which was maintained in men with organic ED (r 2 ¼ 0.62, Po0.0001). In cannabis consumers, a direct relationship between HOMA-IR and VOP was also found (r 2 ¼ 0.74, Po0.0001). Receiver-operating characteristic (ROC) curve analysis revealed that VOP values below 17.22 ml min À1 were suggestive for vasculogenic ED. We conclude that early endothelial damage may be induced by chronic cannabis use (and endocannabinoid system activation); insulin resistance may be the hallmark of early endothelial dysfunction and may concur to determine vascular ED in the absence of obesity. Further studies are warranted to establish a direct relationship between cannabis abuse, onset of insulin resistance and development of vascular ED.

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“…This observation indicated the existence of an endothelial non-CB1/non-CB2 receptor, which is now referred to as abn-cbd receptor, or endothelial anandamide receptor. The presence of such receptors was also confirmed in rabbit aortic ring preparations and rat aortic endothelial cells (143,154), as well as in rabbit pulmonary arterial strips (221). In the CNS, microglial abn-cbd receptors mediate neuroprotective effects (119) and regulate cell migration (247).…”

Section: Biosynthesis and Receptors Of Endocannabinoids In Cells Invomentioning

confidence: 74%

Endocannabinoids in cerebrovascular regulation

Benyó

Ruisanchez

Leszl-Ishiguro

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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The cerebral blood flow is tightly regulated by myogenic, endothelial, metabolic, and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain central nervous system disorders, like hemorrhagic and ischemic stroke, traumatic brain injury, and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e., smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia, and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins [i.e., the cannabinoid 1 and 2 (CB1 and CB2) receptors and the transient receptor potential vanilloid type 1 ion channel]. Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g., in conscious restrained animals or during hypoxia and hypercapnia), cannabinoid receptor activation was shown to induce a reduction of the cerebral blood flow, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g., subarachnoid hemorrhage, as well as traumatic and ischemic brain injury), activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation. cerebral circulation; endocannabinoids; cannabinoid receptors; TRPV1 channel; neurovascular unit THE CEREBRAL VASCULATURE HAS two main homeostatic functions: 1) to adjust the local blood supply to the eventually rapidly changing metabolic demands of neurons; and 2) to maintain an optimal extracellular environment in the brain. The former function is realized by the regulation of the local cerebral blood flow (CBF), whereas the latter is achieved by the maintenance of the blood-brain barrier (BBB) and related transport mechanisms. The endocannabinoid system has been implicated as an important regulatory component in both of these cerebrovascular functions. The roles of endocannabinoids and cannabinoid receptors in the BBB have been reviewed recently (237). Here we aim to overview our knowledge on the endocannabinoid-mediated regulation of cerebral circulation.

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Anandamide-Mediated CB₁/CB₂Cannabinoid Receptor-Independent Nitric Oxide Production in Rabbit Aortic Endothelial Cells

Cited by 46 publications

References 39 publications

Modulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury

Modulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury

Early endothelial dysfunction as a marker of vasculogenic erectile dysfunction in young habitual cannabis users

Endocannabinoids in cerebrovascular regulation

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Anandamide-Mediated CB1/CB2Cannabinoid Receptor-Independent Nitric Oxide Production in Rabbit Aortic Endothelial Cells

Cited by 46 publications

References 39 publications

Modulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury

Modulation of the balance between cannabinoid CB1 and CB2 receptor activation during cerebral ischemic/reperfusion injury

Early endothelial dysfunction as a marker of vasculogenic erectile dysfunction in young habitual cannabis users

Endocannabinoids in cerebrovascular regulation

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Anandamide-Mediated CB₁/CB₂Cannabinoid Receptor-Independent Nitric Oxide Production in Rabbit Aortic Endothelial Cells