APStracts 3:0228H, 1996.

Nitric oxide synthase activity in brain and endothelium: relation to hypercapnic rise of cerebral blood flow in rats. Fabricius, Martin, Inger Rubin, Magnus Bundgaard, and Martin Lauritzen. Department of Medical Physiology, University of Copenhagen, Laboratory of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Department of Medical Biochemistry, University of Copenhagen, Department of Clinical Neurophysiology, Glostrup Hospital, Glostrup, Denmark

APStracts 3:0228H, 1996.

We examined whether attenuation of the hypercapnic increase of cerebral blood flow (CBF) associated with nitric oxide synthase (NOS) inhibition was related to local neuronal or aortic endothelial NOS activity, or local endothelial/neuronal NOS-dependent vasodilation. Halothane anaesthetized rats were ventilated, and CBF was measured by laser-Doppler flowmetry over the parietal and cerebellar cortex. I.v. NG-nitro-L-arginine (L-NNA) (30 mg/kg) inhibited brain and aortic NOS activity by 67-70%. Topical L-NNA (1mM) inhibited brain NOS activity by 91-94%, while aortic NOS activity remained constant. In contrast i.v. L-NNA attenuated the hypercapnic CBF rise much more efficiently than topical L-NNA. 7-nitroindazole, another NOS inhibitor, attenuated endothelial and neuronal NOS activity equally well, and inhibited the hypercapnic CBF increase as effectively as L -NNA.Topical L-NNA and 7-nitroindazole abolished local eNOS dependent vasodilation after 15 min, while hypercapnic CBF was only slightly reduced. L-NNA injected into the tissue abolished nNOS dependent vasodilation while hypercapnic CBF was unchanged. The findings suggest that local NOS activity, whether neuronal or endothelial, is unimportant for the hypercapnic rise of CBF.

Received 19 December 1995; accepted in final form 14 May 1996.
APS Manuscript Number H1185-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96