Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle.
Cannabinoids elicit hypotension mainly via activated CB(1) receptors and show complex cardiovascular actions. Effects on human heart muscle have not been studied yet. Isolated human atrial heart muscle preparations were stimulated by electrical field with 1 Hz to contract isometrically at optimal length and were challenged with the endogenous cannabinoid arachidonyl ethanolamide (anandamide), the metabolically stable analogue R-methanandamide, and the potent synthetic CB(1) receptor agonist HU-210. Anandamide dose-dependently decreased systolic force (82.2 +/- 4.8% and 60.8 +/- 6.8% of maximal systolic force for 0.1 and 1 microM, respectively, P < 0.05). The selective CB(1) receptor antagonist AM-251 (1 microM, P < 0.05), but not the CB(2) receptor antagonist, AM-630 (1 microM), the nitric oxide synthase inhibitor N omega-nitro-l-arginine methyl ester (l-NAME) (500 microM), or the cyclooxygenase inhibitor indomethacin (100 microM), prevented the effect. Contrary to indomethacin, l-NAME alone showed negative inotropic effects (72.1 +/- 3.54%, P < 0.001). The R-methanandamide (1 microM: 50.4 +/- 3.5%, P < 0.001) and HU-210 (1 microM: 60.1 +/- 3.8%, P < 0.001) had similar negative inotropic effects. The existence of CB(1) receptors on heart muscle was verified using Western blot analysis and immunofluorescence staining. The conclusion is that anandamide, R-methanandamide, and HU-210 decrease contractile performance in human atrial muscle via CB(1) receptors.
Bonz
Andreas
A
Medizinische Klinik, Abteilung für Herz und Thoraxchirurgie der Universität Würzburg, Würzburg, Germany.
Laser
Martin
M
Küllmer
Sina
S
Kniesch
Silke
S
Babin-Ebell
Jörg
J
Popp
Verena
V
Ertl
Georg
G
Wagner
Jens Andreas
JA
D016275:Atrial Function / Q000187:drug effects* / Q000502:physiology; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology*; D003864:Depression, Chemical; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000378:metabolism*
D002186:Cannabinoids; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug