TY - JOUR
T1 - The endogenous lipid N-arachidonoyl glycine is hypotensive and nitric oxide-cGMP-dependent vasorelaxant
AU - Al Suleimani, Yousuf M.
AU - Al Mahruqi, Ahmed S.
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2017
Y1 - 2017
N2 - N-arachidonoyl glycine (NAGLY), is the endogenous lipid that activates the G protein-couple receptor 18 (GPR18) with vasodilatory activity in resistance arteries. This study investigates its hemodynamic effects and mechanisms of vasorelaxation. Hemodynamic effects of NAGLY in rats were assessed using a Biopac system and its vascular responses were assessed using a wire myograph. NAGLY (1 mg/kg) decreased blood pressure by 69.4±5.5% and reduced renal blood flow by 88±12% and the effects were not sensitive to inhibition by O-1918 (3 mg/kg). In resistant vessels, NAGLY (1–30 µM) induced concentration- and endothelium-dependent vasorelaxation and the effect was inhibited by the nitric oxide synthase inhibitor, L-NAME (300 µM), a cGMP synthase inhibitor, ODQ (10 µM), the antagonists of “endothelial anandamide” receptor, rimonabant (3 µM) and O-1918 (10 µM) and the inhibitor of Na+/Ca2+exchanger (NCX), KB-R7943 (10 µM). On the other hand, NAGLY-induced vasorelaxation was not affected by CID 16020046 (GPR55 antagonist), AM 251 (cannabinoid CB1receptor antagonist), AM 630 (cannabinoid CB2receptor antagonist), capsazepine (TRPV1 antagonist), indomethacin (cyclooxygenase inhibitor), TRAM34 (IKCa channel blocker), iberiotoxin (BKCa channel blocker) and GW9662 (PPARɤ antagonist). At low concentrations of carbachol, NAGLY potentiated carbachol-induced vasorelaxation. NAGLY is an endothelium-dependent vasodilator and hypotensive lipid. The vasorelaxation is predominantly via activation of nitric oxide-cGMP pathway and NCX and probably mediated by the "endothelial anandamide” receptor, while the hypotensive effect of NAGLY appears not to involve the anandamide receptor. NAGLY also potentiates carbachol-induced vasorelaxation, the mechanism of which might involve stimulation of NO release.
AB - N-arachidonoyl glycine (NAGLY), is the endogenous lipid that activates the G protein-couple receptor 18 (GPR18) with vasodilatory activity in resistance arteries. This study investigates its hemodynamic effects and mechanisms of vasorelaxation. Hemodynamic effects of NAGLY in rats were assessed using a Biopac system and its vascular responses were assessed using a wire myograph. NAGLY (1 mg/kg) decreased blood pressure by 69.4±5.5% and reduced renal blood flow by 88±12% and the effects were not sensitive to inhibition by O-1918 (3 mg/kg). In resistant vessels, NAGLY (1–30 µM) induced concentration- and endothelium-dependent vasorelaxation and the effect was inhibited by the nitric oxide synthase inhibitor, L-NAME (300 µM), a cGMP synthase inhibitor, ODQ (10 µM), the antagonists of “endothelial anandamide” receptor, rimonabant (3 µM) and O-1918 (10 µM) and the inhibitor of Na+/Ca2+exchanger (NCX), KB-R7943 (10 µM). On the other hand, NAGLY-induced vasorelaxation was not affected by CID 16020046 (GPR55 antagonist), AM 251 (cannabinoid CB1receptor antagonist), AM 630 (cannabinoid CB2receptor antagonist), capsazepine (TRPV1 antagonist), indomethacin (cyclooxygenase inhibitor), TRAM34 (IKCa channel blocker), iberiotoxin (BKCa channel blocker) and GW9662 (PPARɤ antagonist). At low concentrations of carbachol, NAGLY potentiated carbachol-induced vasorelaxation. NAGLY is an endothelium-dependent vasodilator and hypotensive lipid. The vasorelaxation is predominantly via activation of nitric oxide-cGMP pathway and NCX and probably mediated by the "endothelial anandamide” receptor, while the hypotensive effect of NAGLY appears not to involve the anandamide receptor. NAGLY also potentiates carbachol-induced vasorelaxation, the mechanism of which might involve stimulation of NO release.
KW - Hypotensive
KW - N-arachidonoyl glycine
KW - Na/Caexchanger
KW - Nitric oxide
KW - Vasorelaxation
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U2 - 10.1016/j.ejphar.2016.11.040
DO - 10.1016/j.ejphar.2016.11.040
M3 - Article
C2 - 27890711
AN - SCOPUS:85000716805
SN - 0014-2999
VL - 794
SP - 209
EP - 215
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -