Bioassay of endothelium-derived hyperpolarizing factor with abolishment of nitric oxide and the role of gap junctions in the porcine coronary circulation

Qin Yang; Zhi-Dong Ge; Cheng-Qin Yang; Yu Huang; Guo-Wei He

doi:10.1002/ddr.10137

Bioassay of endothelium-derived hyperpolarizing factor with abolishment of nitric oxide and the role of gap junctions in the porcine coronary circulation

Qin Yang
, Zhi-Dong Ge
, Cheng-Qin Yang
, Yu Huang
, Guo-Wei He

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

21 Citations (Scopus)

Abstract

Previous bioassays of endothelium-derived hyperpolarizing factor (EDHF) were partially related to the residual nitric oxide (NO) resistant to NO synthase inhibitors. Further, the role of gap junctions in EDHF is controversial. We performed a bioassay of EDHF with abolishment of NO production by using the NOS inhibitor N^G-nitro-L-arginine (L-NNA) plus the NO scavenger hemoglobin (Hb) and examined the role of gap junctions/K⁺ channels related to EDHF in porcine coronary large and microarteries in an organ chamber/myograph. Bradykinin (BK)-induced EDHF-mediated relaxation and hyperpolarization (by a microelectrode) were studied with indomethacin (7 μM), L-NNA (300 μM), and Hb (20 μM). NO concentrations ([NO]) were measured electrochemically. In large coronary arteries, BK increased [NO] (9.3±1.7 nM vs. 166.7±18.3 nM, P<0.01) that was significantly reduced by L-NNA (49.3±7.8 nM, P<0.01) and eliminated by Hb, and hyperpolarized the downstream endothelium-denuded artery by 9.0±1.4 mV (P<0.01) that was reduced but not abolished by L-NNA and Hb (5.6±0.7 mV, P<0.01). In microarteries, elimination of NO decreased but did not abolish the hyperpolarization (-63.8±1.5 mV vs. -56.9±1.6 mV, P=0.01) and relaxation (70.2±5.7% vs. 42.3±4.4%, P<0.01). Charybdotoxin (0.1 μM) and apamin (0.5 μM), but neither glybenclimide (3 μM) nor gap junction inhibitors (18α-glycyrrhetinic acid, 1-heptanol, and gap 27) reduced the EDHF-mediated response. We conclude that in porcine coronary arteries, with the abolishment of NO by NOS inhibitors plus the NO scavenger Hb, the non-NO EDHF exists and is transferable from an endothelium-intact artery to an endothelium-denuded artery. Compared with the significant involvement of calcium-activated K⁺ channels, the gap junctions may only play a minimal role in the EDHF-mediated response even in the microcirculation of the porcine coronary artery. © 2003 Wiley-Liss, Inc.

Original language	English
Pages (from-to)	99-110
Journal	Drug Development Research
Volume	58
Issue number	1
DOIs	https://doi.org/10.1002/ddr.10137
Publication status	Published - 1 Jan 2003
Externally published	Yes

Bibliographical note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

Research Keywords

Circulatory physiology
Coronary circulation
EDHF
Endothelial factors
Gap junctions
K-channel
Nitric oxide

Access Output

10.1002/ddr.10137

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

Cite this

@article{07b945fc4db0466693a3860d61dd6a7a,

title = "Bioassay of endothelium-derived hyperpolarizing factor with abolishment of nitric oxide and the role of gap junctions in the porcine coronary circulation",

abstract = "Previous bioassays of endothelium-derived hyperpolarizing factor (EDHF) were partially related to the residual nitric oxide (NO) resistant to NO synthase inhibitors. Further, the role of gap junctions in EDHF is controversial. We performed a bioassay of EDHF with abolishment of NO production by using the NOS inhibitor NG-nitro-L-arginine (L-NNA) plus the NO scavenger hemoglobin (Hb) and examined the role of gap junctions/K+ channels related to EDHF in porcine coronary large and microarteries in an organ chamber/myograph. Bradykinin (BK)-induced EDHF-mediated relaxation and hyperpolarization (by a microelectrode) were studied with indomethacin (7 μM), L-NNA (300 μM), and Hb (20 μM). NO concentrations ([NO]) were measured electrochemically. In large coronary arteries, BK increased [NO] (9.3±1.7 nM vs. 166.7±18.3 nM, P<0.01) that was significantly reduced by L-NNA (49.3±7.8 nM, P<0.01) and eliminated by Hb, and hyperpolarized the downstream endothelium-denuded artery by 9.0±1.4 mV (P<0.01) that was reduced but not abolished by L-NNA and Hb (5.6±0.7 mV, P<0.01). In microarteries, elimination of NO decreased but did not abolish the hyperpolarization (-63.8±1.5 mV vs. -56.9±1.6 mV, P=0.01) and relaxation (70.2±5.7\% vs. 42.3±4.4\%, P<0.01). Charybdotoxin (0.1 μM) and apamin (0.5 μM), but neither glybenclimide (3 μM) nor gap junction inhibitors (18α-glycyrrhetinic acid, 1-heptanol, and gap 27) reduced the EDHF-mediated response. We conclude that in porcine coronary arteries, with the abolishment of NO by NOS inhibitors plus the NO scavenger Hb, the non-NO EDHF exists and is transferable from an endothelium-intact artery to an endothelium-denuded artery. Compared with the significant involvement of calcium-activated K+ channels, the gap junctions may only play a minimal role in the EDHF-mediated response even in the microcirculation of the porcine coronary artery. {\textcopyright} 2003 Wiley-Liss, Inc.",

keywords = "Circulatory physiology, Coronary circulation, EDHF, Endothelial factors, Gap junctions, K-channel, Nitric oxide",

author = "Qin Yang and Zhi-Dong Ge and Cheng-Qin Yang and Yu Huang and Guo-Wei He",

note = "Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].",

year = "2003",

month = jan,

day = "1",

doi = "10.1002/ddr.10137",

language = "English",

volume = "58",

pages = "99--110",

journal = "Drug Development Research",

issn = "0272-4391",

publisher = "John Wiley \& Sons",

number = "1",

}

Bioassay of endothelium-derived hyperpolarizing factor with abolishment of nitric oxide and the role of gap junctions in the porcine coronary circulation. / Yang, Qin; Ge, Zhi-Dong; Yang, Cheng-Qin et al.
In: Drug Development Research, Vol. 58, No. 1, 01.01.2003, p. 99-110.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Bioassay of endothelium-derived hyperpolarizing factor with abolishment of nitric oxide and the role of gap junctions in the porcine coronary circulation

AU - Yang, Qin

AU - Ge, Zhi-Dong

AU - Yang, Cheng-Qin

AU - Huang, Yu

AU - He, Guo-Wei

N1 - Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Previous bioassays of endothelium-derived hyperpolarizing factor (EDHF) were partially related to the residual nitric oxide (NO) resistant to NO synthase inhibitors. Further, the role of gap junctions in EDHF is controversial. We performed a bioassay of EDHF with abolishment of NO production by using the NOS inhibitor NG-nitro-L-arginine (L-NNA) plus the NO scavenger hemoglobin (Hb) and examined the role of gap junctions/K+ channels related to EDHF in porcine coronary large and microarteries in an organ chamber/myograph. Bradykinin (BK)-induced EDHF-mediated relaxation and hyperpolarization (by a microelectrode) were studied with indomethacin (7 μM), L-NNA (300 μM), and Hb (20 μM). NO concentrations ([NO]) were measured electrochemically. In large coronary arteries, BK increased [NO] (9.3±1.7 nM vs. 166.7±18.3 nM, P<0.01) that was significantly reduced by L-NNA (49.3±7.8 nM, P<0.01) and eliminated by Hb, and hyperpolarized the downstream endothelium-denuded artery by 9.0±1.4 mV (P<0.01) that was reduced but not abolished by L-NNA and Hb (5.6±0.7 mV, P<0.01). In microarteries, elimination of NO decreased but did not abolish the hyperpolarization (-63.8±1.5 mV vs. -56.9±1.6 mV, P=0.01) and relaxation (70.2±5.7% vs. 42.3±4.4%, P<0.01). Charybdotoxin (0.1 μM) and apamin (0.5 μM), but neither glybenclimide (3 μM) nor gap junction inhibitors (18α-glycyrrhetinic acid, 1-heptanol, and gap 27) reduced the EDHF-mediated response. We conclude that in porcine coronary arteries, with the abolishment of NO by NOS inhibitors plus the NO scavenger Hb, the non-NO EDHF exists and is transferable from an endothelium-intact artery to an endothelium-denuded artery. Compared with the significant involvement of calcium-activated K+ channels, the gap junctions may only play a minimal role in the EDHF-mediated response even in the microcirculation of the porcine coronary artery. © 2003 Wiley-Liss, Inc.

AB - Previous bioassays of endothelium-derived hyperpolarizing factor (EDHF) were partially related to the residual nitric oxide (NO) resistant to NO synthase inhibitors. Further, the role of gap junctions in EDHF is controversial. We performed a bioassay of EDHF with abolishment of NO production by using the NOS inhibitor NG-nitro-L-arginine (L-NNA) plus the NO scavenger hemoglobin (Hb) and examined the role of gap junctions/K+ channels related to EDHF in porcine coronary large and microarteries in an organ chamber/myograph. Bradykinin (BK)-induced EDHF-mediated relaxation and hyperpolarization (by a microelectrode) were studied with indomethacin (7 μM), L-NNA (300 μM), and Hb (20 μM). NO concentrations ([NO]) were measured electrochemically. In large coronary arteries, BK increased [NO] (9.3±1.7 nM vs. 166.7±18.3 nM, P<0.01) that was significantly reduced by L-NNA (49.3±7.8 nM, P<0.01) and eliminated by Hb, and hyperpolarized the downstream endothelium-denuded artery by 9.0±1.4 mV (P<0.01) that was reduced but not abolished by L-NNA and Hb (5.6±0.7 mV, P<0.01). In microarteries, elimination of NO decreased but did not abolish the hyperpolarization (-63.8±1.5 mV vs. -56.9±1.6 mV, P=0.01) and relaxation (70.2±5.7% vs. 42.3±4.4%, P<0.01). Charybdotoxin (0.1 μM) and apamin (0.5 μM), but neither glybenclimide (3 μM) nor gap junction inhibitors (18α-glycyrrhetinic acid, 1-heptanol, and gap 27) reduced the EDHF-mediated response. We conclude that in porcine coronary arteries, with the abolishment of NO by NOS inhibitors plus the NO scavenger Hb, the non-NO EDHF exists and is transferable from an endothelium-intact artery to an endothelium-denuded artery. Compared with the significant involvement of calcium-activated K+ channels, the gap junctions may only play a minimal role in the EDHF-mediated response even in the microcirculation of the porcine coronary artery. © 2003 Wiley-Liss, Inc.

KW - Circulatory physiology

KW - Coronary circulation

KW - EDHF

KW - Endothelial factors

KW - Gap junctions

KW - K-channel

KW - Nitric oxide

UR - https://www.scopus.com/pages/publications/0037282441

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-0037282441&origin=recordpage

U2 - 10.1002/ddr.10137

DO - 10.1002/ddr.10137

M3 - RGC 21 - Publication in refereed journal

SN - 0272-4391

VL - 58

SP - 99

EP - 110

JO - Drug Development Research

JF - Drug Development Research

IS - 1

ER -

Bioassay of endothelium-derived hyperpolarizing factor with abolishment of nitric oxide and the role of gap junctions in the porcine coronary circulation

Abstract

Bibliographical note

Research Keywords

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Cite this