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2-Arachidonylglycerol acting on CB1 cannabinoid receptors mediates delayed cardioprotection induced by nitric oxide in rat isolated hearts.
J Cardiovasc Pharmacol 2006; 47(5):650-5JC

Abstract

Endocannabinoids have been implicated in protective effects in the heart and brain, but the mechanism of possible infarct-size-reducing effects remains controversial. Using a model of delayed preconditioning (PC), rats received the nitric oxide (NO) donor nitroglycerin (0.15 mg/h/kg) for 24 hours via transdermal application. Two days later, rat isolated perfused hearts were subjected to global, no-flow ischemia (20 min), and reperfusion (120 min). Cannabinoid receptor antagonists were given before no-flow throughout the protocol. Endocannabinoids were detected by liquid chromatography and mass spectrometry. NO-induced PC reduced the left ventricular infarct size from 40.9 +/- 3.9% to 27.5 +/- 3.8% (P < 0.05). Treatment with the specific CB1 cannabinoid receptor antagonist AM-251 (0.3 microM) prevented the protective effect of PC on infarct size (40.2 +/- 4.7%, P > 0.05 vs. controls). On the contrary, the specific CB2 receptor antagonist AM-630 (0.3 microM) did not alter infarct size (31.6 +/- 6.3%, P > 0.05 vs. PC alone). Recovery of left ventricular developed pressure and coronary flow was incomplete in control and NO-pretreated hearts and not consistently altered by cannabinoid receptor antagonists. PC increased the heart tissue content of the endocannabinoid 2-arachidonylglycerol (2-AG) from 4.6 +/- 1.0 nmol/g in controls to 12.0 +/- 2.1 nmol/g (P < 0.05). Tissue levels of the endocannabinoid arachidonylethanolamide (anandamide) remained unchanged (19.8 +/- 3.9 pmol/g vs. 19.5 +/- 4.8 pmol/g). 2-AG (1 microM) or its metabolically stable derivative noladinether (0.1 microM), given 30 minutes before ischemia/reperfusion in unpreconditioned hearts, mimicked the cardioprotective effects of PC and reduced infarct size. We conclude that delayed PC through transdermal nitroglycerin application increases the production of the endocannabinoid 2-AG which elicits protective effects against myocardial infarction via CB1 cannabinoid receptors which represents one new mechanism of NO-mediated PC.

Authors+Show Affiliations

Department of Internal Medicine 1, Center of Cardiovascular Medicine, University of Würzburg, Würzburg, Germany. wagner_j@klinik.uni-wuerzburg.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16775503

Citation

Wagner, Jens A., et al. "2-Arachidonylglycerol Acting On CB1 Cannabinoid Receptors Mediates Delayed Cardioprotection Induced By Nitric Oxide in Rat Isolated Hearts." Journal of Cardiovascular Pharmacology, vol. 47, no. 5, 2006, pp. 650-5.
Wagner JA, Abesser M, Harvey-White J, et al. 2-Arachidonylglycerol acting on CB1 cannabinoid receptors mediates delayed cardioprotection induced by nitric oxide in rat isolated hearts. J Cardiovasc Pharmacol. 2006;47(5):650-5.
Wagner, J. A., Abesser, M., Harvey-White, J., & Ertl, G. (2006). 2-Arachidonylglycerol acting on CB1 cannabinoid receptors mediates delayed cardioprotection induced by nitric oxide in rat isolated hearts. Journal of Cardiovascular Pharmacology, 47(5), pp. 650-5.
Wagner JA, et al. 2-Arachidonylglycerol Acting On CB1 Cannabinoid Receptors Mediates Delayed Cardioprotection Induced By Nitric Oxide in Rat Isolated Hearts. J Cardiovasc Pharmacol. 2006;47(5):650-5. PubMed PMID: 16775503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 2-Arachidonylglycerol acting on CB1 cannabinoid receptors mediates delayed cardioprotection induced by nitric oxide in rat isolated hearts. AU - Wagner,Jens A, AU - Abesser,Marco, AU - Harvey-White,Judith, AU - Ertl,Georg, PY - 2006/6/16/pubmed PY - 2006/11/7/medline PY - 2006/6/16/entrez SP - 650 EP - 5 JF - Journal of cardiovascular pharmacology JO - J. Cardiovasc. Pharmacol. VL - 47 IS - 5 N2 - Endocannabinoids have been implicated in protective effects in the heart and brain, but the mechanism of possible infarct-size-reducing effects remains controversial. Using a model of delayed preconditioning (PC), rats received the nitric oxide (NO) donor nitroglycerin (0.15 mg/h/kg) for 24 hours via transdermal application. Two days later, rat isolated perfused hearts were subjected to global, no-flow ischemia (20 min), and reperfusion (120 min). Cannabinoid receptor antagonists were given before no-flow throughout the protocol. Endocannabinoids were detected by liquid chromatography and mass spectrometry. NO-induced PC reduced the left ventricular infarct size from 40.9 +/- 3.9% to 27.5 +/- 3.8% (P < 0.05). Treatment with the specific CB1 cannabinoid receptor antagonist AM-251 (0.3 microM) prevented the protective effect of PC on infarct size (40.2 +/- 4.7%, P > 0.05 vs. controls). On the contrary, the specific CB2 receptor antagonist AM-630 (0.3 microM) did not alter infarct size (31.6 +/- 6.3%, P > 0.05 vs. PC alone). Recovery of left ventricular developed pressure and coronary flow was incomplete in control and NO-pretreated hearts and not consistently altered by cannabinoid receptor antagonists. PC increased the heart tissue content of the endocannabinoid 2-arachidonylglycerol (2-AG) from 4.6 +/- 1.0 nmol/g in controls to 12.0 +/- 2.1 nmol/g (P < 0.05). Tissue levels of the endocannabinoid arachidonylethanolamide (anandamide) remained unchanged (19.8 +/- 3.9 pmol/g vs. 19.5 +/- 4.8 pmol/g). 2-AG (1 microM) or its metabolically stable derivative noladinether (0.1 microM), given 30 minutes before ischemia/reperfusion in unpreconditioned hearts, mimicked the cardioprotective effects of PC and reduced infarct size. We conclude that delayed PC through transdermal nitroglycerin application increases the production of the endocannabinoid 2-AG which elicits protective effects against myocardial infarction via CB1 cannabinoid receptors which represents one new mechanism of NO-mediated PC. SN - 0160-2446 UR - https://www.unboundmedicine.com/medline/citation/16775503/2_Arachidonylglycerol_acting_on_CB1_cannabinoid_receptors_mediates_delayed_cardioprotection_induced_by_nitric_oxide_in_rat_isolated_hearts_ L2 - http://Insights.ovid.com/pubmed?pmid=16775503 DB - PRIME DP - Unbound Medicine ER -