Z D Ge1, X H Zhang, P C Fung, G W He. 1. Grantham Hospital, Department of Surgery, The University of Hong Kong, Aberdeen, Hong Kong SAR, China.
Abstract
OBJECTIVE: It is controversial whether endothelium-dependent relaxation resistance to inhibitors of nitric oxide (NO) and prostacyclin synthases is completely attributed to endothelium-derived hyperpolarizing factor (EDHF). This study examined NO release and K+ channels involved in endothelium-dependent relaxation and hyperpolarization resistance to N(G)-nitro-L-arginine (L-NNA) and indomethacin in coronary arteries with emphasis on the microarteries. METHODS: NO release, isometric force, and membrane potential of porcine coronary arteries were measured using a NO-specific electrode, wire myograph, and microelectrode, respectively. RESULTS: In large arteries pretreated with indomethacin, bradykinin (BK) evoked a rise in [NO] from 5.5+/-2.4 nM to 105.0+/-19.6 nM and hyperpolarization. L-NNA treatment significantly reduced the BK-stimulated rise in [NO] to 32.1+/-11.3 nM but did not affect the hyperpolarization. In the presence of indomethacin and L-NNA, U46619 contracted and depolarized (from -51+/-3 mV to -30+/-4 mV) vascular smooth muscle in microarteries. The addition of BK produced dose-dependent relaxation (maximal: 70.2+/-5.7%) and repolarization (membrane potential: -50+/-4 mV). Oxyhemoglobin eliminated indomethacin and L-NNA-resistance rise in [NO] but not relaxation (42.3+/-4.4%) and repolarization (-40+/-2 mV) by BK. Tetraethylammonium, charybdotoxin, and iberiotoxin partially decreased the BK-induced responses. Apamin alone did not affect the relaxation by BK; however, in combination with charybdotoxin it almost completely abolished the BK-induced relaxation and hyperpolarization. CONCLUSIONS: In porcine coronary arteries, both EDHF and NO contribute to BK-induced relaxation resistance to indomethacin and L-NNA. Large conductance Ca2+-activated K+ channels (BK(Ca)) may play an important role in mediating the BK-induced responses and small conductance Ca2+-activated K+ channels might function as 'backup' mechanisms when BK(Ca) is curtailed.
OBJECTIVE: It is controversial whether endothelium-dependent relaxation resistance to inhibitors of nitric oxide (NO) and prostacyclin synthases is completely attributed to endothelium-derived hyperpolarizing factor (EDHF). This study examined NO release and K+ channels involved in endothelium-dependent relaxation and hyperpolarization resistance to N(G)-nitro-L-arginine (L-NNA) and indomethacin in coronary arteries with emphasis on the microarteries. METHODS: NO release, isometric force, and membrane potential of porcine coronary arteries were measured using a NO-specific electrode, wire myograph, and microelectrode, respectively. RESULTS: In large arteries pretreated with indomethacin, bradykinin (BK) evoked a rise in [NO] from 5.5+/-2.4 nM to 105.0+/-19.6 nM and hyperpolarization. L-NNA treatment significantly reduced the BK-stimulated rise in [NO] to 32.1+/-11.3 nM but did not affect the hyperpolarization. In the presence of indomethacin and L-NNA, U46619 contracted and depolarized (from -51+/-3 mV to -30+/-4 mV) vascular smooth muscle in microarteries. The addition of BK produced dose-dependent relaxation (maximal: 70.2+/-5.7%) and repolarization (membrane potential: -50+/-4 mV). Oxyhemoglobin eliminated indomethacin and L-NNA-resistance rise in [NO] but not relaxation (42.3+/-4.4%) and repolarization (-40+/-2 mV) by BK. Tetraethylammonium, charybdotoxin, and iberiotoxin partially decreased the BK-induced responses. Apamin alone did not affect the relaxation by BK; however, in combination with charybdotoxin it almost completely abolished the BK-induced relaxation and hyperpolarization. CONCLUSIONS: In porcine coronary arteries, both EDHF and NO contribute to BK-induced relaxation resistance to indomethacin and L-NNA. Large conductance Ca2+-activated K+ channels (BK(Ca)) may play an important role in mediating the BK-induced responses and small conductance Ca2+-activated K+ channels might function as 'backup' mechanisms when BK(Ca) is curtailed.
Authors: Q Yang; A R Hohimer; G D Giraud; D M Van Winkle; M J Underwood; G-W He; L E Davis Journal: Acta Physiol (Oxf) Date: 2008-09-20 Impact factor: 6.311
Authors: Shelley L Baumgardt; Mark Paterson; Thorsten M Leucker; Juan Fang; David X Zhang; Zeljko J Bosnjak; David C Warltier; Judy R Kersten; Zhi-Dong Ge Journal: Circ Heart Fail Date: 2016-01 Impact factor: 8.790
Authors: David C Ellinsworth; Shaun L Sandow; Nilima Shukla; Yanping Liu; Jamie Y Jeremy; David D Gutterman Journal: Microcirculation Date: 2016-01 Impact factor: 2.628