Varying extracellular [K+]

A functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed

Ayotunde S O Adeagbo, Christopher Triggle

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

We describe a simple, functional approach to defining the relative contribution of endothelium-dependent hyperpolarization (presumably mediated by a factor, EDHF) and endothelium-derived nitric oxide (EDNO) to acetylcholine (ACh) and histamine relaxations of isolated perfused rat mesenteric resistance arterial bed. In physiologic salt solution (PSS), ACh- and his-tamine-induced vasodilations of cirazoline-preconstricted mesenteric arterial bed were only partially attenuated by 50 µM Nw-nitro-L-arginine methyl ester (L-NAME). The L-NAME-resistant component was abolished by 0.5 µM apamin but not by 250 nM dendrotoxin or 10 µM glyburide, thus indicating a role for apamin-sensitive K+ channels in mediating the effects of the putative EDHF. Changing membrane potential by varying [K+] decreased L-NAME-resistant vasodilation, and showed a modest L-NAME-induced increase in the basal perfusion pressure that was not observable in normal PSS. Vasodilator responses during cirazoline-induced tonus in 20 mM K+ and normal PSS were superimposable, but responses to ACh and histamine in 20 mM K+ were profoundly more sensitive to L-NAME than were those in normal PSS media. ACh responses during 20-mM K + PSS perfusion and presumably mediated by EDNO and those resistant to L-NAME and putatively mediated by EDHF were antagonized by graded concentrations of p-fluoro-hexahydro-siladifenidol (p-F-HHSiD), but not pirenzepine. Therefore, we concluded that (a) perfused rat mesenteric arterial bed releases both EDHF and EDNO in response to ACh and histamine, (b) EDHF plays a dominant role in maintenance of the basal perfusion pressure in this vascular bed, and (c) both EDHF and EDNO relaxations are mediated by activation of M3 muscarinic cholinoceptors.

Original languageEnglish
Pages (from-to)423-429
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume21
Issue number3
Publication statusPublished - 1993
Externally publishedYes

Fingerprint

NG-Nitroarginine Methyl Ester
Nitric Oxide
Acetylcholine
Salts
Histamine
Apamin
Perfusion
Vasodilation
Pirenzepine
Pressure
Glyburide
Cholinergic Receptors
Vasodilator Agents
Membrane Potentials
Cholinergic Agents
Endothelium
Blood Vessels
endothelium-dependent hyperpolarization factor
Maintenance

Keywords

  • Endothelium-derived hyperpolarizing factor
  • Endothelium-derived nitric oxide
  • Extracellular K
  • L-NAME
  • Perfused rat mesenteric bed

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

@article{8855042435be4ec8acab02dc2af5486d,
title = "Varying extracellular [K+]: A functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed",
abstract = "We describe a simple, functional approach to defining the relative contribution of endothelium-dependent hyperpolarization (presumably mediated by a factor, EDHF) and endothelium-derived nitric oxide (EDNO) to acetylcholine (ACh) and histamine relaxations of isolated perfused rat mesenteric resistance arterial bed. In physiologic salt solution (PSS), ACh- and his-tamine-induced vasodilations of cirazoline-preconstricted mesenteric arterial bed were only partially attenuated by 50 µM Nw-nitro-L-arginine methyl ester (L-NAME). The L-NAME-resistant component was abolished by 0.5 µM apamin but not by 250 nM dendrotoxin or 10 µM glyburide, thus indicating a role for apamin-sensitive K+ channels in mediating the effects of the putative EDHF. Changing membrane potential by varying [K+] decreased L-NAME-resistant vasodilation, and showed a modest L-NAME-induced increase in the basal perfusion pressure that was not observable in normal PSS. Vasodilator responses during cirazoline-induced tonus in 20 mM K+ and normal PSS were superimposable, but responses to ACh and histamine in 20 mM K+ were profoundly more sensitive to L-NAME than were those in normal PSS media. ACh responses during 20-mM K + PSS perfusion and presumably mediated by EDNO and those resistant to L-NAME and putatively mediated by EDHF were antagonized by graded concentrations of p-fluoro-hexahydro-siladifenidol (p-F-HHSiD), but not pirenzepine. Therefore, we concluded that (a) perfused rat mesenteric arterial bed releases both EDHF and EDNO in response to ACh and histamine, (b) EDHF plays a dominant role in maintenance of the basal perfusion pressure in this vascular bed, and (c) both EDHF and EDNO relaxations are mediated by activation of M3 muscarinic cholinoceptors.",
keywords = "Endothelium-derived hyperpolarizing factor, Endothelium-derived nitric oxide, Extracellular K, L-NAME, Perfused rat mesenteric bed",
author = "Adeagbo, {Ayotunde S O} and Christopher Triggle",
year = "1993",
language = "English",
volume = "21",
pages = "423--429",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Varying extracellular [K+]

T2 - A functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed

AU - Adeagbo, Ayotunde S O

AU - Triggle, Christopher

PY - 1993

Y1 - 1993

N2 - We describe a simple, functional approach to defining the relative contribution of endothelium-dependent hyperpolarization (presumably mediated by a factor, EDHF) and endothelium-derived nitric oxide (EDNO) to acetylcholine (ACh) and histamine relaxations of isolated perfused rat mesenteric resistance arterial bed. In physiologic salt solution (PSS), ACh- and his-tamine-induced vasodilations of cirazoline-preconstricted mesenteric arterial bed were only partially attenuated by 50 µM Nw-nitro-L-arginine methyl ester (L-NAME). The L-NAME-resistant component was abolished by 0.5 µM apamin but not by 250 nM dendrotoxin or 10 µM glyburide, thus indicating a role for apamin-sensitive K+ channels in mediating the effects of the putative EDHF. Changing membrane potential by varying [K+] decreased L-NAME-resistant vasodilation, and showed a modest L-NAME-induced increase in the basal perfusion pressure that was not observable in normal PSS. Vasodilator responses during cirazoline-induced tonus in 20 mM K+ and normal PSS were superimposable, but responses to ACh and histamine in 20 mM K+ were profoundly more sensitive to L-NAME than were those in normal PSS media. ACh responses during 20-mM K + PSS perfusion and presumably mediated by EDNO and those resistant to L-NAME and putatively mediated by EDHF were antagonized by graded concentrations of p-fluoro-hexahydro-siladifenidol (p-F-HHSiD), but not pirenzepine. Therefore, we concluded that (a) perfused rat mesenteric arterial bed releases both EDHF and EDNO in response to ACh and histamine, (b) EDHF plays a dominant role in maintenance of the basal perfusion pressure in this vascular bed, and (c) both EDHF and EDNO relaxations are mediated by activation of M3 muscarinic cholinoceptors.

AB - We describe a simple, functional approach to defining the relative contribution of endothelium-dependent hyperpolarization (presumably mediated by a factor, EDHF) and endothelium-derived nitric oxide (EDNO) to acetylcholine (ACh) and histamine relaxations of isolated perfused rat mesenteric resistance arterial bed. In physiologic salt solution (PSS), ACh- and his-tamine-induced vasodilations of cirazoline-preconstricted mesenteric arterial bed were only partially attenuated by 50 µM Nw-nitro-L-arginine methyl ester (L-NAME). The L-NAME-resistant component was abolished by 0.5 µM apamin but not by 250 nM dendrotoxin or 10 µM glyburide, thus indicating a role for apamin-sensitive K+ channels in mediating the effects of the putative EDHF. Changing membrane potential by varying [K+] decreased L-NAME-resistant vasodilation, and showed a modest L-NAME-induced increase in the basal perfusion pressure that was not observable in normal PSS. Vasodilator responses during cirazoline-induced tonus in 20 mM K+ and normal PSS were superimposable, but responses to ACh and histamine in 20 mM K+ were profoundly more sensitive to L-NAME than were those in normal PSS media. ACh responses during 20-mM K + PSS perfusion and presumably mediated by EDNO and those resistant to L-NAME and putatively mediated by EDHF were antagonized by graded concentrations of p-fluoro-hexahydro-siladifenidol (p-F-HHSiD), but not pirenzepine. Therefore, we concluded that (a) perfused rat mesenteric arterial bed releases both EDHF and EDNO in response to ACh and histamine, (b) EDHF plays a dominant role in maintenance of the basal perfusion pressure in this vascular bed, and (c) both EDHF and EDNO relaxations are mediated by activation of M3 muscarinic cholinoceptors.

KW - Endothelium-derived hyperpolarizing factor

KW - Endothelium-derived nitric oxide

KW - Extracellular K

KW - L-NAME

KW - Perfused rat mesenteric bed

UR - http://www.scopus.com/inward/record.url?scp=0027478677&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027478677&partnerID=8YFLogxK

M3 - Article

VL - 21

SP - 423

EP - 429

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 3

ER -