Effect of l-nmma, cromakalim and glibenclamide on cerebral blood flow in hypercapnia and hypoxia. Reid, John M., Alun G. Davies, Frances M. Ashcroft & David J. Paterson. University Laboratory of Physiology, Parks Road, Oxford, OX1 3PT, United Kingdom
APStracts 2:0148H, 1995.
John M. Reid, Alun G. Davies, Frances M. Ashcroft and David J. Paterson. Effect of L-NMMA, glibenclamide and cromakalim on cerebral blood flow during hypoxia and hypercapnia. Sulphonylureas reduce cerebral blood flow (CBF) during hypoxia, but not during hypercapnia, whereas blockers of nitric oxide (NO) synthesis reduce hypercapnic CBF. However, the effect of NO blockers on hypoxic CBF is uncertain. CBF was measured in the cortex of 51 enflurane-anesthetized rats using the hydrogen clearance technique during eucapnia, hypercapnia (PaCO2 65 Torr) and hypoxia (PaO2 40 Torr). CBF increased two-fold in both hypercapnia and hypoxia from eucapnia. Intra-cortical (i.c.) N -monomethyl L-arginine (L-NMMA, 100 M - 5 mM) attenuated both the hypercapnic and hypoxic dilations by 60-70% and L-arginine (300 mg/kg i.v.) partially reversed these effects. Glibenclamide (10 M i.c.) and L-NMMA gave no further attenuation of the hypoxic dilation than L -NMMA alone. Cromakalim (10 M, i.c.) increased CBF in eucapnia, but this was not seen in the presence of glibenclamide. The adenosine antagonist 8-phenyltheophylline did not attenuate the hypoxic dilation. This suggests that NO synthesis plays a major role in the regulation of CBF in hypercapnia and hypoxia. But, the combined effect of glibenclamide and L-NMMA do not further attenuate CBF in hypoxia. 

Received 31 October 1994; accepted in final form 31 March 1995.
APS Manuscript Number H962-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.