Heterogeneous populations of K+ channels mediate EDRF release to flow but not agonists in rabbit aorta.
We have investigated the role of Ca(2+)- and ATP-sensitive K+ channels (KCa and KATP, respectively) in flow- and agonist-stimulated release of endothelium-derived relaxing factor (EDRF). Segments of rabbit abdominal aorta, perfused at constant flow with buffer containing indomethacin, were used as a source of EDRF in cascade bioassay, and responses to endothelium-dependent agonists were studied isometrically in rings of the same tissue in the absence of flow. Apamin, charybdotoxin (ChTX), and tetraethylammonium (TEA) were used to block a variety of low, medium, and high conductance KCa channels, and glibenclamide was used to block KATP channels. The effects of flow pulsatility were studied at pulse frequencies ranging from 0.15 to 9.75 Hz, and time-averaged shear stress was manipulated by adding dextran (80,000 mol wt) to the perfusate to increase its viscosity. Frequency-related EDRF release was maximal at approximately 5 Hz and attenuated by apamin, TEA, and ChTX, but not by glibenclamide. EDRF release stimulated by increased viscosity was attenuated by TEA, ChTX, and glibenclamide, but not by apamin. In marked contrast, EDRF release stimulated by acetylcholine and ATP was unaffected by blockade of either KCa or KATP channels. We conclude that a spectrum of KCa channel subtypes mediates endothelial transduction of the oscillatory component of pulsatile flow and that KATP channels may be additionally involved in the transduction of time-averaged shear stress. In contrast, agonist-stimulated endothelium-dependent relaxation is independent of K+ channel activation in rabbit aorta.
Hutcheson
I R
IR
Department of Diagnostic Radiology, University of Wales College of Medicine, Cardiff, United Kingdom.
Griffith
T M
TM
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000502:physiology*; D001030:Apamin / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001681:Biological Assay; D001920:Bradykinin / Q000494:pharmacology; D018999:Charybdotoxin; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D012604:Scorpion Venoms / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D001030:Apamin; D009569:Nitric Oxide; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D001120:Arginine; D000109:Acetylcholine; D001920:Bradykinin; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester