Does endothelium-derived hyperpolarizing factor play a role in endothelium-dependent component of electrical field stimulation-induced vasorelaxation of rat mesenteric arterial rings?
Electrical field stimulation (EFS)-induced, nonadrenergic, noncholinergic vasodilation was investigated in rat mesenteric arterial rings. Tetrodotoxin (10(-6) M), capsaicin (10(-5) M), or L-NAME (10(-4) M) failed to change the EFS-induced relaxations, whereas they were increased with indomethacin (10(-5) M). Removal of the endothelium caused approximately 20% reduction in the maximum response, whereas precontraction with 40 mM KCI abolished the relaxations at all frequencies. Iberiotoxin (3 x 10(-7) M) attenuated the relaxations in endothelium-intact tissues but blocked completely those in endothelium-denuded arteries. Combination of TRAM-34 (10(-5) M) with apamin (5 x 10(-7) M) and single administrations of NiCI2 (5 x 10(-4) M), ruthenium red (3 x 10(-5) M), and 18[alpha]-glycyrrhetinic acid (10(-4) M) significantly reduced the responses only in endothelium-intact tissues. These data indicate that in rat mesenteric arteries, EFS leads to vasodilation through both endothelium-dependent and endothelium-independent mechanisms. The major component of the relaxation is endothelium independent and seems to occur via BK(Ca) channels, whereas endothelium-dependent component is likely to be mediated by endothelium-derived hyperpolarizing factor rather than nitric oxide, prostacyclin, or a neural substance. We propose that Ca2+ entry into endothelial cells via nonspecific cation channels in response to EFS induces hyperpolarization by activating endothelial IK(Ca) and SK(Ca) channels, which is spread to the smooth muscle via gap junctions to produce relaxation.
Ozkan
Melike Hacer
MH
Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Uma
Serdar
S
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D004558:Electric Stimulation; D004727:Endothelium / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D011464:Epoprostenol; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D008643:Mesentery / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D011720:Pyrazoles; C411671:TRAM 34; D001030:Apamin; D009569:Nitric Oxide; D011464:Epoprostenol; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin