The role of neuronal nitric oxide synthase in regulation of cerebral blood flow in normocapnia and hypercapnia in rats.
The nitric oxide synthase (NOS) inhibitors, nitro-L-arginine, its methyl ester, and N-monomethyl-L-arginine, have been shown to attenuate resting CBF and hypercapnia-induced cerebrovasodilation. Those agents nonspecifically inhibit the endothelial and neuronal NOS (eNOS and nNOS). In the present study, we used a novel nNOS inhibitor, 7-nitroindazole (7-NI) to examine the role of nNOS in CBF during normocapnia and hypercapnia in fentanyl/N2O-anesthetized rats. CBF was monitored using laser-Doppler flowmetry. Administration of 7-NI (80 mg kg-1 i.p.) reduced cortical brain NOS activity by 57%, the resting CBF by 19-27%, and the CBF response to hypercapnia by 60%. The 60% reduction was similar in magnitude to the CBF reductions observed in previous studies in which nonspecific NOS inhibitors were used. In the present study, 7-NI did not increase the MABP. Furthermore, the CBF response to oxotremorine, a blood-brain barrier permeant muscarinic agonist that induces cerebrovasodilation via endothelium-derived NO, was unaffected by 7-NI. These results confirmed that 7-NI does not influence eNOS; they also indicated that the effects of 7-NI on the resting CBF and on the CBF response to hypercapnia in this study were solely related to its inhibitory action on nNOS. The results further suggest that the NO synthesized by the action of nNOS participates in regulation of basal CBF and is the major, if not the only, category of NO contributing to the hypercapnic CBF response.
Wang
Q
Q
Department of Anesthesiology, University of Illinois-Chicago, USA.
Pelligrino
D A
DA
Baughman
V L
VL
Koenig
H M
HM
Albrecht
R F
RF
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006935:Hypercapnia / Q000503:physiopathology*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007191:Indazoles; D002245:Carbon Dioxide; D010095:Oxotremorine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C080122:7-nitroindazole