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 alpha(1)-adrenoceptor agonist-induced oscillatory vasomotion and in limiting vasoconstrictor response to the agonists; however, contribution of EDHF to the alpha(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 degrees 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 Ca2+-activated K+ (K(Ca)) channels by charybdotoxin and apamin caused a further leftward shift in the concentration-response relation in the vessels pretreated with Nomega-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.