Importance of nitric oxide synthase inhibition to the attenuated vascular responses induced by topical L-nitroarginine during vibrissal stimulation.
We assessed the regional cerebral blood flow (rCBF) response to vibrissal stimulation before and after nitric oxide synthase (NOS) inhibitors were topically applied through a closed cranial window placed over the cortical barrel fields in anesthetized Sprague-Dawley rats. In the presence of L-nitroarginine (1 mM), both the maximum and total responses became reduced, but only in those animals demonstrating > 50% inhibition of NOS activity as determined by the conversion of [3H]arginine to [3H]citrulline within homogenates taken from cortical gray matter under the cranial window. The degree of enzyme inhibition depended in part, upon duration after topical application of NOS inhibitor. When > 50%, enzyme inhibition correlated with the decrease in maximum and total rCBF response (p < 0.01). These findings emphasize the merits of assessing enzyme activity after administering NOS inhibitors, and suggest that NO generated from parenchymal NOS activity plays an important role in the cerebrovascular response to physiologic somatosensory stimulation under the stated conditions.
Irikura
K
K
Stroke Research Laboratory, Neurosurgery and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Maynard
K I
KI
Moskowitz
M A
MA
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000201:enzymology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014738:Vibrissae / Q000502:physiology*
D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases