RT Journal Article
SR Electronic
T1 Acute Myocardial Infarction Inhibits the Neurogenic Tachycardic and Vasopressor Response in Rats via Presynaptic Cannabinoid Type 1 Receptor
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 198
OP 205
DO 10.1124/jpet.112.196816
VO 343
IS 1
A1 Rudź, Radosław
A1 Schlicker, Eberhard
A1 Baranowska, Urszula
A1 Marciniak, Justyna
A1 Karabowicz, Piotr
A1 Malinowska, Barbara
YR 2012
UL http://jpet.aspetjournals.org/content/343/1/198.abstract
AB The present study was carried out to examine whether acute experimental myocardial infarction affects the sympathetic transmission to vessels and the heart of pithed rats via a presynaptic mechanism and, if so, to check whether inhibitory presynaptic cannabinoid (CB) receptors and endocannabinoids are involved in this response. In pithed and vagotomized rats, electrical stimulation (0.75 Hz; 1 ms; 50 V; 5 or 15 pulses for increases in heart rate or blood pressure, respectively) of the preganglionic sympathetic nerve fibers or intravenous injection of isoprenaline (0.1 nmol/kg) or noradrenaline (1 nmol/kg) increased heart rate and blood pressure by approximately 50 beats/min and 40 mm Hg, respectively. Ligation of the left coronary artery reduced the electrically (as opposed to the chemically) induced tachycardic and pressor responses by approximately 30 to 40%. The inhibitory effect of myocardial infarction was prevented by the CB1 receptor antagonist rimonabant but not by the CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethyl-bicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyra-zole-3-carboxamide (SR144528) and the transient receptor potential vanilloid 1 receptor antagonist capsazepine. The inhibitory effect of myocardial infarction was slightly enhanced by the inhibitors of anandamide and 2-arachidonyl glycerol degradation, 3′-(aminocarbonyl)[1,1′-biphenyl]-3-yl)-cyclohexylcarbamate (URB597) and 4-nitrophenyl-4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184), respectively. Rimonabant increased myocardial infarction-induced mortality. Our results demonstrate that during the early phase of myocardial infarction the activation of presynaptic CB1 receptors by endogenously formed cannabinoids contributes to the inhibition of the neurogenic tachycardic and vasopressor responses. Thus, the CB1 receptor-mediated inhibition of excessive noradrenaline release from the sympathetic nerve fibers innervating the heart and vessels might play a protective role in myocardial ischemia.