Varying extracellular [K+]: a functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed

J Cardiovasc Pharmacol. 1993 Mar;21(3):423-9.


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 histamine-induced vasodilations of cirazoline-preconstricted mesenteric arterial bed were only partially attenuated by 50 microM Nw-nitro-L-arginine methyl ester (L-NAME). The L-NAME-resistant component was abolished by 0.5 microM apamin but not by 250 nM dendrotoxin or 10 microM 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-fluorohexahydro-siladifenidol (p-F-HHSiD), but not pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Biological Factors / physiology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Histamine / pharmacology
  • In Vitro Techniques
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / physiology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase
  • Potassium / physiology*
  • Potassium Channels / drug effects
  • Rats
  • Receptors, Muscarinic / physiology
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects


  • Biological Factors
  • Potassium Channels
  • Receptors, Muscarinic
  • endothelium-dependent hyperpolarization factor
  • Nitric Oxide
  • Histamine
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Acetylcholine
  • Potassium
  • NG-Nitroarginine Methyl Ester