ABSTRACT
Vasomotor reactions upon focal stimulation of arterioles are conducted along the vascular wall. This study aimed to identify which endothelial autacoid(s) act as mediators of the local and conducted dilator responses. Hitherto, arterioles in the hamster cremaster microcirculation were locally stimulated with acetylcholine or sodium nitroprusside and the resulting changes in diameter were measured using videomicroscopy at the site of application and up to 1.4mm upstream at distant sites. Experiments were also performed after blockade of NO-synthase, cyclooxygenase, P450-monooxygenase or K-channels. Dilatations in response to acetylcholine, but not sodium nitroprusside, were conducted rapidly to upstream sites with diminished amplitude. Maximal amplitudes of acetylcholine-induced dilatations were not attenuated by inhibition of NO-synthase and cyclooxygenase. However, P450-monooxygenase blockers (sulfaphenazole or ODYA) attenuated dilatations at local and distant sites. Charybdotoxin or iberiotoxin attenuated dilatations at the local and remote site after focal application at the stimulation site. In contrast, treatment of the upstream site with these blockers was without any effect. It is concluded that upon local stimulation with acetylcholine a P450monooxygenase product is generated, which induces local dilatation via the activation of Ca2-dependent K-channels and initiates conduction of the dilatation. In contrast to the local site, neither activation of these K-channels nor the synthesis of nitric oxide (NO) or prostaglandins are necessary to dilate the arterioles at remote, distant sites. This suggests that endothelium-derived hyperpolarizing factor (EDHF) serves as an important mediator to initiate conducted dilatations and may act as a key player in the coordination of arteriolar behaviour in the microcirculatory network.
