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 CB(1) receptor antagonist
rimonabant but not by the CB(2) 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 CB(1) receptors by endogenously formed
cannabinoids contributes to the inhibition of the neurogenic tachycardic and vasopressor responses. Thus, the CB(1) 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.