Abstract
An endogenous cannabinoid anandamide (N-arachidonoylethanolamide) has been shown to cause vasodilatation in vitro and a brief vasoconstriction followed by prolonged depressor response in vivo. This study investigated the vascular effects of anandamide and underlying mechanisms in rat mesenteric vascular beds. In preparations with an intact endothelium and active tone, anandamide at low concentrations (0.1 - 1 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation, but at high concentrations (10 nM - 1 μM) elicited an initial and sharp increase in perfusion pressure due to vasoconstriction followed by long-lasting vasodilatation in a concentration-dependent manner. Treatment with SR141716A [cannabinoid-1 (CB 1)-receptor antagonist] blunted both the vasoconstrictor and vasodilator responses. Also, removal of the endothelium and indomethacin (cyclooxygenase inhibitor), but not adrenergic denervation with 6-hydoxydopamine (adrenergic neurotoxin), markedly inhibited the vasoconstrictor response to anandamide, while these treatments did not affect vasodilatation. The vasodilatation, but not vasoconstriction, in response to anandamide was markedly attenuated by capsazepine [ selective antagonist for transient receptor potential vanilloid-1 (TRPV1)], pretreatment with capsaicin [calcitonin gene-related peptide (CGRP)ergic-nerve depletor], or cold-storage denervation. These results suggest that in rat mesenteric vascular beds, anandamide causes CB1-receptor- and prostanoid-mediated endothelium-dependent vasoconstriction and perivascular capsaicin-sensitive CGRPergic nerve-mediated vasodilatation.
| Original language | English |
|---|---|
| Pages (from-to) | 496-505 |
| Number of pages | 10 |
| Journal | Journal of Pharmacological Sciences |
| Volume | 118 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2012 |
Fingerprint
Keywords
- Anandamide
- Cannabinoid-1 receptor
- CGRPergic nerve
- Prostanoid
- Transient receptor potential vanilloid-1
ASJC Scopus subject areas
- Pharmacology
- Molecular Medicine
Cite this
Anandamide induces endothelium-dependent vasoconstriction and CGRPergic nerve-mediated vasodilatation in the rat mesenteric vascular bed. / Tamaki, Chihiro; Nawa, Hideki; Takatori, Shingo; Oda, Sakiko; Sendo, Toshiaki; Zamami, Yoshito; Kawasaki, Hiromu.
In: Journal of Pharmacological Sciences, Vol. 118, No. 4, 2012, p. 496-505.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anandamide induces endothelium-dependent vasoconstriction and CGRPergic nerve-mediated vasodilatation in the rat mesenteric vascular bed
AU - Tamaki, Chihiro
AU - Nawa, Hideki
AU - Takatori, Shingo
AU - Oda, Sakiko
AU - Sendo, Toshiaki
AU - Zamami, Yoshito
AU - Kawasaki, Hiromu
PY - 2012
Y1 - 2012
N2 - An endogenous cannabinoid anandamide (N-arachidonoylethanolamide) has been shown to cause vasodilatation in vitro and a brief vasoconstriction followed by prolonged depressor response in vivo. This study investigated the vascular effects of anandamide and underlying mechanisms in rat mesenteric vascular beds. In preparations with an intact endothelium and active tone, anandamide at low concentrations (0.1 - 1 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation, but at high concentrations (10 nM - 1 μM) elicited an initial and sharp increase in perfusion pressure due to vasoconstriction followed by long-lasting vasodilatation in a concentration-dependent manner. Treatment with SR141716A [cannabinoid-1 (CB 1)-receptor antagonist] blunted both the vasoconstrictor and vasodilator responses. Also, removal of the endothelium and indomethacin (cyclooxygenase inhibitor), but not adrenergic denervation with 6-hydoxydopamine (adrenergic neurotoxin), markedly inhibited the vasoconstrictor response to anandamide, while these treatments did not affect vasodilatation. The vasodilatation, but not vasoconstriction, in response to anandamide was markedly attenuated by capsazepine [ selective antagonist for transient receptor potential vanilloid-1 (TRPV1)], pretreatment with capsaicin [calcitonin gene-related peptide (CGRP)ergic-nerve depletor], or cold-storage denervation. These results suggest that in rat mesenteric vascular beds, anandamide causes CB1-receptor- and prostanoid-mediated endothelium-dependent vasoconstriction and perivascular capsaicin-sensitive CGRPergic nerve-mediated vasodilatation.
AB - An endogenous cannabinoid anandamide (N-arachidonoylethanolamide) has been shown to cause vasodilatation in vitro and a brief vasoconstriction followed by prolonged depressor response in vivo. This study investigated the vascular effects of anandamide and underlying mechanisms in rat mesenteric vascular beds. In preparations with an intact endothelium and active tone, anandamide at low concentrations (0.1 - 1 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation, but at high concentrations (10 nM - 1 μM) elicited an initial and sharp increase in perfusion pressure due to vasoconstriction followed by long-lasting vasodilatation in a concentration-dependent manner. Treatment with SR141716A [cannabinoid-1 (CB 1)-receptor antagonist] blunted both the vasoconstrictor and vasodilator responses. Also, removal of the endothelium and indomethacin (cyclooxygenase inhibitor), but not adrenergic denervation with 6-hydoxydopamine (adrenergic neurotoxin), markedly inhibited the vasoconstrictor response to anandamide, while these treatments did not affect vasodilatation. The vasodilatation, but not vasoconstriction, in response to anandamide was markedly attenuated by capsazepine [ selective antagonist for transient receptor potential vanilloid-1 (TRPV1)], pretreatment with capsaicin [calcitonin gene-related peptide (CGRP)ergic-nerve depletor], or cold-storage denervation. These results suggest that in rat mesenteric vascular beds, anandamide causes CB1-receptor- and prostanoid-mediated endothelium-dependent vasoconstriction and perivascular capsaicin-sensitive CGRPergic nerve-mediated vasodilatation.
KW - Anandamide
KW - Cannabinoid-1 receptor
KW - CGRPergic nerve
KW - Prostanoid
KW - Transient receptor potential vanilloid-1
UR - http://www.scopus.com/inward/record.url?scp=84867192990&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867192990&partnerID=8YFLogxK
U2 - 10.1254/jphs.11236FP
DO - 10.1254/jphs.11236FP
M3 - Article
C2 - 22510966
AN - SCOPUS:84867192990
VL - 118
SP - 496
EP - 505
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 4
ER -