Role of endocannabinoids and cannabinoid-1 receptors in cerebrocortical blood flow regulation

Autor: Éva Ruisanchez, András Iring, Rita Benkő, Péter Sándor, Pal Pacher, Béla Horváth, Zoltán Járai, Miriam Leszl-Ishiguro, Zsombor Lacza, Vincenzo Di Marzo, Zoltán Benyó
Rok vydání: 2012
Předmět:
Male
Cannabinoid receptor
Anatomy and Physiology
medicine.medical_treatment
Hemodynamics
lcsh:Medicine
Cardiovascular System
Hypercapnia
Cerebral circulation
Piperidines
Receptor
Cannabinoid
CB1
Heart Rate
Laser-Doppler Flowmetry
lcsh:Science
Hypoxia
Multidisciplinary
Neurochemistry
Endocannabinoid system
Neurology
Cerebrovascular Circulation
Hypertension
Circulatory Physiology
Medicine
lipids (amino acids
peptides
and proteins)
medicine.symptom
Neurochemicals
medicine.drug
Research Article
AM251
medicine.medical_specialty
Cerebrovascular Diseases
Arachidonic Acids
Internal medicine
medicine
Animals
Arterial Pressure
Rats
Wistar
Biology
business.industry
lcsh:R
Hypoxia (medical)
Rats
Blood pressure
Endocrinology
nervous system
Pyrazoles
lcsh:Q
Cannabinoid
business
Endocannabinoids
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 1, p e53390 (2013)
ISSN: 1932-6203
Popis: Background: Endocannabinoids are among the most intensively studied lipid mediators of cardiovascular functions. In the present study the effects of decreased and increased activity of the endocannabinoid system (achieved by cannabinoid-1 (CB1) receptor blockade and inhibition of cannabinoid reuptake, respectively) on the systemic and cerebral circulation were analyzed under steady-state physiological conditions and during hypoxia and hypercapnia (H/H). Methodology/Principal Findings: In anesthetized spontaneously ventilating rats the CB1-receptor antagonist/inverse agonist AM-251 (10 mg/kg, i.v.) failed to influence blood pressure (BP), cerebrocortical blood flow (CoBF, measured by laserDoppler flowmetry) or arterial blood gas levels. In contrast, the putative cannabinoid reuptake inhibitor AM-404 (10 mg/kg, i.v.) induced triphasic responses, some of which could be blocked by AM-251. Hypertension during phase I was resistant to AM-251, whereas the concomitant CoBF-increase was attenuated. In contrast, hypotension during phase III was sensitive to AM-251, whereas the concomitant CoBF-decrease was not. Therefore, CoBF autoregulation appeared to shift towards higher BP levels after CB1-blockade. During phase II H/H developed due to respiratory depression, which could be inhibited by AM251. Interestingly, however, the concomitant rise in CoBF remained unchanged after AM-251, indicating that CB1-blockade potentially enhanced the reactivity of the CoBF to H/H. In accordance with this hypothesis, AM-251 induced a significant enhancement of the CoBF responses during controlled stepwise H/H. Conclusion/Significance: Under resting physiological conditions CB1-receptor mediated mechanisms appear to have limited influence on systemic or cerebral circulation. Enhancement of endocannabinoid levels, however, induces transient CB1-independent hypertension and sustained CB1-mediated hypotension. Furthermore, enhanced endocannabinoid activity results in respiratory depression in a CB1-dependent manner. Finally, our data indicate for the first time the involvement of the endocannabinoid system and CB1-receptors in the regulation of the cerebral circulation during H/H and also raise the possibility of their contribution to the autoregulation of CoBF.
Databáze: OpenAIRE
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