Role of Endothelium-derived Hyperpolarizing Factor in Phenylephrine-induced Oscillatory Vasomotion in Rat Small Mesenteric Artery

Background: In small mesenteric arteries, endothelium-derived hyperpolarizing factor (EDHF) in addition to endothelium-derived relaxing factors (EDRFs) including NO plays an important role in acetylcholine-induced vasodilation. It has been reported that EDRFs play an important role in at -adrenoceptor agonist-induced oscillatory vasomotion and in limiting vasoconstrictor response to the agonist; however, contribution of EDHF to the α 1 -agonist-induced oscillation is unknown. Methods: Rat small mesenteric arteries were isolated and cannulated at each end with a glass micropipette. The vessels were immersed in a bath (37°C) containing physiologic saline solution. Changes in vessel diameter were measured using an optical density video detection system. Results: Denudation of the endothelium and inhibition of NO synthesis caused a leftward shift in the concentration-response relation for phenylephrine in the mesenteric arteries, whereas inhibition of cyclooxygenase by indomethacin had no effect. Blockade of Ca 2+ -activated K + (K Ca ) channels by charybdotoxin and apamin caused a further leftward shift in the concentration-response relation in the vessels pretreated with N ω -nitro-L-arginine methylester and indomethacin. Phenylephrine at concentrations higher than 10 -6 M caused endothelium-dependent oscillatory vasomotion, which was reduced but not abolished after combined inhibition of the cyclooxygenase and NO synthase pathways. However, the K Ca channel blockers completely abolished the remaining component of oscillation. Conclusions: Endothelially-derived NO is an important modulator of sustained agonist-induced vasoconstriction. NO, as well as endothelially-derived cyclooxygenase products and EDHF, also contribute significantly to phenylephrine-induced oscillatory vasomotion.