NO synthase blockade induces chaotic cerebral vasomotion via activation ofthromboxane receptors

Background and Purpose-Instability of the vascular tone (vasomotion) develo ps in several cerebrovascular diseases associated with endothelial dysfunct ion. The aim of the present study was to characterize cerebral vasomotion i nduced by diminished NO production with quantitative evaluation and chaos a nalysis. We tested the hypothesis that activation of thromboxane receptors mediates chaotic vasomotion after NO synthase (NOS) inhibition. Methods-Measurements of vascular tension were carried out in isolated rat m iddle cerebral arteries. The extent of vasomotion was characterized by tens ion instability, whereas vasomotion complexity was assessed by chaos analys is. Results-Blocking the basal NO release byN(omega)-nitro-L-arginine (L-NA) in duced vasomotion, which was further enhanced and became irregular after UTP administration. The NO donor sodium nitroprusside was able to reverse this effect, and stable steady-state conditions reappeared. The guanylyl cyclas e inhibitor 1H-(1,2,4)oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) or coapplica tion of ODQ and L-NA had an effect identical to that of L-NA alone. Vasocon striction by K+ failed to induce vasomotion in intact vessels or in the pre sence of L-NA or ODQ. The thromboxane receptor antagonist ICI 192605 dose-d ependently attenuated the vasomotion induced by L-NA and UTP, and the throm boxane-receptor agonist U-46619 induced significant vasomotion in intact ve ssels. Conclusions-The lack of NO in cerebral vessels provokes vulnerability to ch aotic vasomotion, which can be triggered by the administration of UTP, wher eas excess NO reverses it to stable conditions. The vasomotion after blocka de of the NO-cGMP pathway is mediated by activation of thromboxane receptor s.