Ethanol dilates coronary arteries and increases coronary flow via transient receptor potential vanilloid 1 and calcitonin gene-related peptide.
OBJECTIVE
Consumption of alcoholic beverages reduces the risk of coronary artery disease (CAD), and epidemiological studies have shown that ethanol per se is protective. However, the mechanism by which ethanol exerts protection is not fully known. Ethanol can stimulate neuropeptide-containing primary sensory neurons via the activation of transient receptor potential vanilloid 1 (TRPV1). Here, we have studied whether ethanol-mediated TRPV1 activation causes the release of calcitonin gene-related peptide (CGRP) that, via dilatation of coronary arteries and other mechanisms, may protect the heart from CAD.


RESULTS
Ethanol caused a marked relaxation of small-sized porcine isolated coronary (0.008-2.37%, w/v) and human isolated gastro-epiploic (0.0008-2.37%, w/v) arteries in vitro, an effect that was abolished by capsaicin-desensitization, the TRPV1 antagonist capsazepine, and the CGRP receptor antagonist, CGRP(8-37). In guinea-pig isolated and perfused hearts, ethanol (0.079-0.79%, w/v) increased baseline coronary flow in a concentration-dependent manner: 0.237% ethanol doubled baseline coronary flow. This effect was also abolished by capsaicin-desensitization, capsazepine, and CGRP((8-37)). Finally, the ethanol-induced increase in CGRP release from guinea-pig isolated and perfused hearts and from slices of porcine coronary arteries was abolished by capsaicin-desensitization and by capsazepine. Similar functional and neurochemical results were obtained in all preparations with capsaicin.


CONCLUSIONS
Ethanol, at low concentrations not dissimilar from those found in blood following low to moderate consumption of alcoholic beverages, releases CGRP within coronary arteries via stimulation of TRPV1 on perivascular sensory nerve terminals. Ethanol-induced release of CGRP may contribute to the reduction in the risk of CAD associated with alcohol consumption by various mechanisms, including the increase in coronary flow and arterial dilatation.
Center of Excellence for the Study of Inflammation, University of Ferrara, Italy.
David
D
Gazzieri
Marcello
M
Trevisani
Francesca
F
Tarantini
Paolo
P
Bechi
Giulio
G
Masotti
Gian Franco
GF
Gensini
Sergio
S
Castellani
Niccolo'
N
Marchionni
Pierangelo
P
Geppetti
Selena
S
Harrison
D000818:Animals; D001158:Arteries; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D050916:TRPV Cation Channels / Q000378:metabolism*; D046509:Tissue Culture Techniques; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D014665:Vasodilator Agents; C058636:calcitonin gene-related peptide (8-37); D000431:Ethanol; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin