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Endothelial mediators of the acetylcholine-induced relaxation of the rat femoral artery.
Vascul Pharmacol. 2006 May; 44(5):299-308.VP

Abstract

This study examined endothelium-derived mediators of acetylcholine-induced relaxation in male rat femoral arteries. Arterial rings were suspended in a myograph for the measurement of isometric force. The generation of hydrogen peroxide (H2O2) in endothelial cells was detected using the fluorescent probe, 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester. N(G)-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor) and 1H-[1,2,4]oxadiazolo[4,2-alpha]quinoxalin-1-one (ODQ, guanylate cyclase inhibitor) alone or in combination with indomethacin (cycloxygenase inhibitor) diminished acetylcholine-induced endothelium-dependent relaxation to a similar extent. A small relaxation to acetylcholine in 60 mM KCl-constricted rings was abolished by L-NAME. Acetylcholine-induced relaxation was reduced by charybdotoxin plus apamin (intermediate- and small-conductance Ca2+-activated K+ channel blockers, respectively) or by 30 mM KCl. Both ouabain (Na+/K+ ATPase inhibitor) and BaCl2 (K(IR) channel blocker) also inhibited the relaxation albeit to a lesser degree. In the presence of L-NAME, ODQ plus indomethacin, charybdotoxin plus apamin or ouabain plus BaCl2 produced further inhibition. Catalase attenuated acetylcholine-induced relaxations and this attenuation was prevented by 3-amino-1,2,4-triazole (catalase inhibitor). Catalase did not affect acetylcholine-induced relaxations in rings treated with L-NAME or ODQ. Acetylcholine increased the dichlorofluorescein fluorescence intensity in native endothelial cells and this effect was abolished by catalase and by L-NAME. Exogenous H2O2 caused endothelium-independent relaxation that was slightly inhibited by iberiotoxin, ODQ or significantly reduced by elevated KCl, and abolished by catalase. The present results indicate that in addition to nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF, sensitive to charybdotoxin plus apamin, ouabain, and BaCl2), the endothelium of rat femoral artery can release H2O2 in response to acetylcholine, which was sensitive to L-NAME. Thus, the eNOS-dependent H2O2 is likely to be the third mediator of acetylcholine-mediated relaxations in rat femoral arteries.

Authors+Show Affiliations

Li Ka Shing Institute of Health Sciences and Department of Physiology, Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16527547

Citation

Leung, Hok Sum, et al. "Endothelial Mediators of the Acetylcholine-induced Relaxation of the Rat Femoral Artery." Vascular Pharmacology, vol. 44, no. 5, 2006, pp. 299-308.
Leung HS, Leung FP, Yao X, et al. Endothelial mediators of the acetylcholine-induced relaxation of the rat femoral artery. Vascul Pharmacol. 2006;44(5):299-308.
Leung, H. S., Leung, F. P., Yao, X., Ko, W. H., Chen, Z. Y., Vanhoutte, P. M., & Huang, Y. (2006). Endothelial mediators of the acetylcholine-induced relaxation of the rat femoral artery. Vascular Pharmacology, 44(5), 299-308.
Leung HS, et al. Endothelial Mediators of the Acetylcholine-induced Relaxation of the Rat Femoral Artery. Vascul Pharmacol. 2006;44(5):299-308. PubMed PMID: 16527547.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelial mediators of the acetylcholine-induced relaxation of the rat femoral artery. AU - Leung,Hok Sum, AU - Leung,Fung Ping, AU - Yao,Xiaoqiang, AU - Ko,Wing Hung, AU - Chen,Zhen-Yu, AU - Vanhoutte,Paul M, AU - Huang,Yu, Y1 - 2006/03/09/ PY - 2005/10/01/received PY - 2006/01/01/accepted PY - 2006/3/11/pubmed PY - 2006/12/12/medline PY - 2006/3/11/entrez SP - 299 EP - 308 JF - Vascular pharmacology JO - Vascul Pharmacol VL - 44 IS - 5 N2 - This study examined endothelium-derived mediators of acetylcholine-induced relaxation in male rat femoral arteries. Arterial rings were suspended in a myograph for the measurement of isometric force. The generation of hydrogen peroxide (H2O2) in endothelial cells was detected using the fluorescent probe, 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester. N(G)-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor) and 1H-[1,2,4]oxadiazolo[4,2-alpha]quinoxalin-1-one (ODQ, guanylate cyclase inhibitor) alone or in combination with indomethacin (cycloxygenase inhibitor) diminished acetylcholine-induced endothelium-dependent relaxation to a similar extent. A small relaxation to acetylcholine in 60 mM KCl-constricted rings was abolished by L-NAME. Acetylcholine-induced relaxation was reduced by charybdotoxin plus apamin (intermediate- and small-conductance Ca2+-activated K+ channel blockers, respectively) or by 30 mM KCl. Both ouabain (Na+/K+ ATPase inhibitor) and BaCl2 (K(IR) channel blocker) also inhibited the relaxation albeit to a lesser degree. In the presence of L-NAME, ODQ plus indomethacin, charybdotoxin plus apamin or ouabain plus BaCl2 produced further inhibition. Catalase attenuated acetylcholine-induced relaxations and this attenuation was prevented by 3-amino-1,2,4-triazole (catalase inhibitor). Catalase did not affect acetylcholine-induced relaxations in rings treated with L-NAME or ODQ. Acetylcholine increased the dichlorofluorescein fluorescence intensity in native endothelial cells and this effect was abolished by catalase and by L-NAME. Exogenous H2O2 caused endothelium-independent relaxation that was slightly inhibited by iberiotoxin, ODQ or significantly reduced by elevated KCl, and abolished by catalase. The present results indicate that in addition to nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF, sensitive to charybdotoxin plus apamin, ouabain, and BaCl2), the endothelium of rat femoral artery can release H2O2 in response to acetylcholine, which was sensitive to L-NAME. Thus, the eNOS-dependent H2O2 is likely to be the third mediator of acetylcholine-mediated relaxations in rat femoral arteries. SN - 1537-1891 UR - https://www.unboundmedicine.com/medline/citation/16527547/Endothelial_mediators_of_the_acetylcholine_induced_relaxation_of_the_rat_femoral_artery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1537-1891(06)00043-7 DB - PRIME DP - Unbound Medicine ER -