Varying extracellular [K+]: a functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed.
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)
Adeagbo
A S
AS
Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada.
Triggle
C R
CR
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011976:Receptors, Muscarinic / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001685:Biological Factors; D015221:Potassium Channels; D011976:Receptors, Muscarinic; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D006632:Histamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester