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

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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
Issue number3
Publication statusPublished - 1993
Externally publishedYes



  • 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

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