Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production.
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 microM THC for 24 h prevented hypoxia-induced lactate dehydrogenase (LDH) leakage and preserved the morphological distribution of alpha-sarcomeric actin. The antagonist for the CB2 (10 microM), but not CB1 receptor antagonist (10 microM) 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 microM) 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.
Shmist
Yelena A
YA
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Goncharov
Igor
I
Eichler
Maor
M
Shneyvays
Vladimir
V
Isaac
Ahuva
A
Vogel
Zvi
Z
Shainberg
Asher
A
D000199:Actins / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D013759:Dronabinol / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000199:Actins; D018712:Analgesics, Non-Narcotic; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D009569:Nitric Oxide; D013759:Dronabinol; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester