Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production

Yelena A. Shmist, Igor Goncharov, Maor Eichler, Vladimir Shneyvays, Ahuva Isaac, Zvi Vogel, Asher Shainberg

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59 Scopus citations


Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has a beneficial effect on the cardiovascular system during stress conditions, but the defence mechanism is still unclear. The present study was designed to investigate the central (CB1) and the peripheral (CB2) cannabinoid receptor expression in neonatal cardiomyoctes and possible function in the cardioprotection of THC from hypoxia. Pre-treatment of cardiomyocytes that were grown in vitro with 0.1-10 μM THC for 24 h prevented hypoxia-induced lactate dehydrogenase (LDH) leakage and preserved the morphological distribution of α-sarcomeric actin. The antagonist for the CB2 (10 μM), but not CB1 receptor antagonist (10 μM) abolished the protective effect of THC. In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express CB2, but not CB1 receptors. Involvement of NO in the signal transduction pathway activated by THC through CB2 was examined. It was found that THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via CB2 receptors. L-NAME (NOS inhibitor, 100 μM) prevented the cardioprotection provided by THC. Taken together, our findings suggest that THC protects cardiac cells against hypoxia via CB2 receptor activation by induction of NO production. An NO mechanism occurs also in the classical pre-conditioning process; therefore, THC probably pre-trains the cardiomyocytes to hypoxic conditions.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalMolecular and Cellular Biochemistry
Issue number1-2
StatePublished - Feb 2006

Bibliographical note

Funding Information:
We would like to thank T. Zinman for valuable technical assistance. This research was partially supported by a grant from the Israeli Ministry of Health and by the Yeshaya Horowitz Association at Bar-Ilan University.


  • Hypoxia
  • Nitric oxide
  • Pre-conditioning
  • Receptors
  • Signal transduction


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