Nitric oxide and prostaglandins interact to mediate arteriolar dilation during cortical spreading depression . Meng, Wei, David M. Colonna, Joseph R. Tobin, and David W. Busija. Departments of Physiology and Pharmacology, *Anesthesiology, and Neuroscience Program, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1083
APStracts 2:0030H, 1995.
We examined whether blockade of prostaglandin synthesis by indomethacin could attenuate the effect of nitric oxide synthase (NOS) inhibition on cerebral arteriolar dilation during cortical spreading depression (CSD). CSD was induced by microinjection of 5% (670 mM) KCl onto the cerebral cortex of anesthetized adult rabbits. A closed cranial window and intravital microscopy were used to measure pial arteriolar diameter, and NOS activity was determined by the conversion assay of [14C]arginine to [14C]citrulline. CSD dilated pial arterioles by 47+/-3% (baseline= 80-88 _m) (N=21, P<0.05), and inhibition of NOS by NG-nitro-L-arginine (L-NNA) (15 mg/kg, IV) reduced dilation during CSD by over one-half (N=8, P<0.05) without altering the onset latency to CSD. After indomethacin administration (15 mg/kg, IV), CSD dilated arterioles from 73+/-2 _m to 152+/-6 _m (N=4, p<0.05). However, following administration of both indomethacin and L-NNA (N=5), CSD-induced arteriolar dilation was not different from the situation where indomethacin alone was given. Thus, indomethacin completely abolished L-NNA's inhibitory effect upon CSD-induced dilation. Administration of L-NNA inhibited NOS activity in brain cortex almost completely (N=8, P<0.05), while indomethacin itself had no effect (N=8). In addition, L-NNA inhibited topical acetylcholine (10-5M)-induced arteriolar dilation (N=3, P<0.05) and this effect was not altered by indomethacin (N=4). In summary, L-NNA reduced arteriolar dilation during CSD. However, following administration of indomethacin, L-NNA does not reduce CSD -induced arteriolar dilation. 

Received 12 October 1994; accepted in final form 2 February 1995.
APS Manuscript Number H913-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.