Abstract
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.
Footnotes
This work was supported by the Polish Ministry of Science and Higher Education [Grant 1339/POL/2006/30]; the Medical University of Białystok [Grant 3-13538F] (to B.M.); and the Copernicus Award from the Foundation for Polish Science (to B.M.) and the German Research Foundation (to E.S.).
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
ABBREVIATIONS:
- MI
- myocardial infarction
- AEA
- anandamide
- 2-AG
- 2-arachidonyl glycerol
- BP
- blood pressure
- DBP
- diastolic BP
- MBP
- mean BP
- SBP
- systolic BP
- CB
- cannabinoid
- DMSO
- dimethyl sulfoxide
- ES
- electrical stimulation
- FAAH
- fatty acid amide hydrolase
- HR
- heart rate
- ISO
- isoprenaline
- JZL184
- 4-nitrophenyl-4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate
- MAGL
- monoacylglycerol lipase
- NA
- noradrenaline
- PGF2α
- prostaglandin F2α
- S
- stimuli
- SR144528
- 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
- TRPV
- transient receptor potential vanilloid
- URB597
- 3′-(aminocarbonyl)[1,1′-biphenyl]-3-yl)-cyclohexylcarbamate
- VP
- vasopressin.
- Received May 28, 2012.
- Accepted July 12, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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