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Background and Purpose: Instability of the vascular tone (vasomotion) develops in several cerebrovascular diseases associated with endothelial dysfunction. The aim of the present study was to characterize cerebral vasomotion induced by diminished NO production with quantitative evaluation and chaos analysis. 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 middle cerebral arteries. The extent of vasomotion was characterized by tension instability, whereas vasomotion complexity was assessed by chaos analysis., Results: Blocking the basal NO release by N(omega)-nitro-L-arginine (L-NA) induced 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 cyclase inhibitor 1H-(1,2,4)oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) or coapplication of ODQ and L-NA had an effect identical to that of L-NA alone. Vasoconstriction by K(+) failed to induce vasomotion in intact vessels or in the presence of L-NA or ODQ. The thromboxane receptor antagonist ICI 192605 dose-dependently attenuated the vasomotion induced by L-NA and UTP, and the thromboxane-receptor agonist U-46619 induced significant vasomotion in intact vessels., Conclusions: The lack of NO in cerebral vessels provokes vulnerability to chaotic vasomotion, which can be triggered by the administration of UTP, whereas excess NO reverses it to stable conditions. The vasomotion after blockade of the NO-cGMP pathway is mediated by activation of thromboxane receptors.

The interaction between uridine-5'-triphosphate (UTP) and prostanoids was studied in isolated rat middle cerebral arteries (MCAs). The strong contractions in MCA segments induced by UTP were weakened significantly by indomethacin and more markedly by the thromboxane receptor antagonist ICI 192605. Thromboxane A(2) (TXA(2)) release by MCAs was below the detection limit of the chemiluminescence enzyme immunoassay, but increased TXA(2) formation was detected in basilar arteries in the presence of UTP. Prostacyclin (PGI(2)) formation by MCAs also increased in the presence of UTP. These results suggest that UTP stimulates the release of both TXA(2) and PGI(2) from the rat MCA but the vascular effect of TXA(2) is dominant.

The role of the neuronal isoform of the nitric oxide (NO) synthase (nNOS) in the regulation of the cerebrovascular tone was studied in vitro. Selective inhibition of nNOS by 7-nitro indazole monosodium salt (7-NINA) failed to alter the resting tension and the relaxant effect of bradykinin in isolated rat middle cerebral arteries. These results indicate that 1./ 7-NINA is selective for nNOS and 2./ cerebrovascular nNOS is involved neither in the resting NO production nor in the mediation of the relaxant effect of bradykinin. Therefore, nNOS-derived NO that contributes to the maintenance of the resting cerebral blood flow in vivo appears to be released from neurons and/or glial cells.