The endothelium-derived hyperpolarising factor (EDHF) in isolated bovine choroidal arteries.
The present study reports of an endothelium-dependent and NO- and prostanoid-independent relaxation in isolated choroidal arteries, and evaluates the hypothesis of an endothelium-derived hyperpolarising factor (EDHF) playing a role in the choroidal circulation. Choroidal arteries were isolated from bovine eyes and mounted in a small vessel wire-myograph for isometric tension recording. Concentration-response curves for acetylcholine (0.1nM-10microM) were constructed in isolated choroidal arteries contracted with 10microM norepinephrine. Acetylcholine induced a concentration-dependent relaxation in the choroidal arteries. The presence of the NO-synthase inhibitor L-NA and the cyclo-oxygenase inhibitor indomethacin only had a limited effect on this relaxation. All further experiments were performed in the presence of L-NA and indomethacin, in order to study the NO- and prostanoid-independent part of the acetylcholine-relaxations. Both removal of the vascular endothelium or the presence of an increased K(+) concentration in the organ bath abolished the NO- and prostanoid-independent part of the acetylcholine-relaxations. The presence of TEA, a rather non-specific K(+) channel blocker, significantly reduced the acetylcholine-relaxations. Simultaneous application of apamin (an inhibitor of small-conductance Ca(2+)-activated K(+) channels) and charybdotoxin (an inhibitor of intermediate- and large-conductance Ca(2+)-activated K(+) channels) abolished the acetylcholine-induced relaxation and even resulted in a concentration-dependent contraction. Transmembrane potential recordings in isolated choroidal arteries revealed a clear membrane hyperpolarisation in the vascular smooth muscle cells of isolated choroidal arteries. It was therefore concluded that the acetylcholine-induced relaxation of choroidal arteries in the presence of NO-synthase and cyclo-oxygenase inhibitors is mediated by an endothelium-derived hyperpolarising factor. This EDHF seems to be of more importance than endothelium-derived NO or prostanoids.
Delaey
Christophe
C
Department of Physiology and Pathophysiology, Ghent University, De Pintelaan 185, Blok B, B-9000 Ghent, Belgium.
Boussery
Koen
K
Breyne
Joke
J
Vanheel
Bert
B
Van de Voorde
Johan
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001685:Biological Factors / Q000378:metabolism*; D002417:Cattle; D002829:Choroid / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; D026902:Potassium Channel Blockers; C067410:endothelium-dependent hyperpolarization factor; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D011188:Potassium