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Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery.
Pharmacol Res 2012; 66(3):251-9PR

Abstract

Endocannabinoids exhibit vasodilatory properties and reduce blood pressure in vivo. However, the influence and mechanism of action of the prominent endocannabinoid, anandamide (AEA), in pulmonary arteries are not known. The present study determined the vascular response to AEA in isolated rat pulmonary arteries. AEA relaxed rat pulmonary arteries that were pre-constricted with U-46619. This relaxation was reduced by the following conditions:removal of the endothelium; in KCl pre-constricted preparations; in the presence of the potassium channel (K(Ca)) blockers, tetraethylammonium and the combination of charybdotoxin and apamin, and the prostacyclin receptor antagonist, RO1138452. Inhibitors of cyclooxygenase (indomethacin), nitric oxide (NO) synthase (N(G)-nitro-l-arginine methyl ester) and fatty acid amide hydrolase (URB597) alone or in combination diminished AEA-induced relaxation in endothelium-intact vessels. The remaining experiments were performed in the presence of URB597 to eliminate the influence of AEA metabolites. Antagonists of the endothelial cannabinoid receptor (CB(x)), O-1918 and cannabidiol, attenuated the AEA-induced response. Antagonists of CB(1), CB(2) and TRPV1 receptors, AM251, AM630 and capsazepine, respectively, did not modify the AEA-induced response. A reference activator of CB(x) receptors, abnormal cannabidiol, mimicked the receptor-mediated AEA effects. The present study demonstrated that AEA relaxed rat pulmonary arteries in an endothelium-dependent fashion via the activation of the O-1918-sensitive CB(x) receptor and/or prostacyclin-like vasoactive products of AEA. One or both of these mechanisms may involve K(Ca) or the NO pathway.

Authors+Show Affiliations

Zakład Fizjologii i Patofizjologii Doświadczalnej, Uniwersytet Medyczny w Białymstoku, ul. Mickiewicza 2A, 15-222 Białystok, Poland. mabar@umb.edu.plNo 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

22627170

Citation

Baranowska-Kuczko, Marta, et al. "Endothelium-dependent Mechanisms of the Vasodilatory Effect of the Endocannabinoid, Anandamide, in the Rat Pulmonary Artery." Pharmacological Research, vol. 66, no. 3, 2012, pp. 251-9.
Baranowska-Kuczko M, MacLean MR, Kozłowska H, et al. Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery. Pharmacol Res. 2012;66(3):251-9.
Baranowska-Kuczko, M., MacLean, M. R., Kozłowska, H., & Malinowska, B. (2012). Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery. Pharmacological Research, 66(3), pp. 251-9. doi:10.1016/j.phrs.2012.05.004.
Baranowska-Kuczko M, et al. Endothelium-dependent Mechanisms of the Vasodilatory Effect of the Endocannabinoid, Anandamide, in the Rat Pulmonary Artery. Pharmacol Res. 2012;66(3):251-9. PubMed PMID: 22627170.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelium-dependent mechanisms of the vasodilatory effect of the endocannabinoid, anandamide, in the rat pulmonary artery. AU - Baranowska-Kuczko,Marta, AU - MacLean,Margaret R, AU - Kozłowska,Hanna, AU - Malinowska,Barbara, Y1 - 2012/05/22/ PY - 2012/01/26/received PY - 2012/04/25/revised PY - 2012/05/14/accepted PY - 2012/5/26/entrez PY - 2012/5/26/pubmed PY - 2012/12/12/medline SP - 251 EP - 9 JF - Pharmacological research JO - Pharmacol. Res. VL - 66 IS - 3 N2 - Endocannabinoids exhibit vasodilatory properties and reduce blood pressure in vivo. However, the influence and mechanism of action of the prominent endocannabinoid, anandamide (AEA), in pulmonary arteries are not known. The present study determined the vascular response to AEA in isolated rat pulmonary arteries. AEA relaxed rat pulmonary arteries that were pre-constricted with U-46619. This relaxation was reduced by the following conditions:removal of the endothelium; in KCl pre-constricted preparations; in the presence of the potassium channel (K(Ca)) blockers, tetraethylammonium and the combination of charybdotoxin and apamin, and the prostacyclin receptor antagonist, RO1138452. Inhibitors of cyclooxygenase (indomethacin), nitric oxide (NO) synthase (N(G)-nitro-l-arginine methyl ester) and fatty acid amide hydrolase (URB597) alone or in combination diminished AEA-induced relaxation in endothelium-intact vessels. The remaining experiments were performed in the presence of URB597 to eliminate the influence of AEA metabolites. Antagonists of the endothelial cannabinoid receptor (CB(x)), O-1918 and cannabidiol, attenuated the AEA-induced response. Antagonists of CB(1), CB(2) and TRPV1 receptors, AM251, AM630 and capsazepine, respectively, did not modify the AEA-induced response. A reference activator of CB(x) receptors, abnormal cannabidiol, mimicked the receptor-mediated AEA effects. The present study demonstrated that AEA relaxed rat pulmonary arteries in an endothelium-dependent fashion via the activation of the O-1918-sensitive CB(x) receptor and/or prostacyclin-like vasoactive products of AEA. One or both of these mechanisms may involve K(Ca) or the NO pathway. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/22627170/Endothelium_dependent_mechanisms_of_the_vasodilatory_effect_of_the_endocannabinoid_anandamide_in_the_rat_pulmonary_artery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(12)00112-0 DB - PRIME DP - Unbound Medicine ER -