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(Stroke. 2001;32:2609.)
© 2001 American Heart Association, Inc.

Original Contributions

NO Synthase Blockade Induces Chaotic Cerebral Vasomotion via Activation of Thromboxane Receptors

Zsombor Lacza, MD; Péter Hermán, MD; Christoph Görlach, PhD; Tibor Hortobágyi, MD, PhD; Péter Sándor, MD, PhD; Michael Wahl, MD, PhD Zoltán Benyó, MD, PhD

From the Department of Physiology (Z.L., C.G., T.H., M.W., Z.B.), Ludwig-Maximilians University, Munich, Germany, and the Institute of Human Physiology and Clinical Experimental Research (Z.L., P.H., P.S., Z.B.), Semmelweis University, Budapest, Hungary.

Reprint requests to Dr Zoltán Benyó, Semmelweis University, Institute of Human Physiology and Clinical Experimental Research, POB 448, H-1446 Budapest, Hungary. E-mail benyo{at}elet2.sote.hu

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-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.

Key Words: cerebral circulation • nitric oxide • thromboxanes • vasomotor system • rats

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