title: Effects of moderate, central fluid percussion traumatic brain injury on nitric oxide synthase activity in rats.
abstract: Experimental traumatic brain injury (TBI) damages cerebral vascular endothelium and reduces cerebral blood flow (CBF). The nitric oxide synthase (NOS) substrate, L-arginine, prevents CBF reductions after TBI, but the mechanism is not known. This study examined the possibility that post-traumatic hypoperfusion is due to reductions in the substrate sensitivity of NOS which are overcome by L-arginine. Isoflurane-anesthetized rats were prepared for TBI (midline fluid-percussion, 2.2 atm), sham-TBI, or no surgery (control), and were decapitated 30 min after injury or sham injury. The brains were removed and homogenized or minced for measurements of crude soluble or cell-dependent stimulated NOS activity, respectively. Baseline arterial oxygen, carbon dioxide, pH, or hemoglobin levels did not differ among control, sham, or TBI groups. Total cortical soluble NOS activity in TBI-treated rats was not significantly different from either untreated or sham groups when 0.45 microM or 1.5 microM L-arginine was added. Also, there were no differences in cell-dependent NOS activity among the three groups stimulated by 300 microM N-methyl-D-aspartate, 50 mM K+, or 10 microM ionomycin. These data suggest that TBI reduces CBF by a mechanism other than altering the substrate specificity or activation of nNOS.
authors.affiliation: Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Alagarsamy
authors.forename: D S
authors.initials: DS
authors.lastname: DeWitt
authors.forename: K M
authors.initials: KM
authors.lastname: Johnson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D001930:Brain Injuries / Q000201:enzymology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists; D015759:Ionomycin; D007476:Ionophores; D008297:Male; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018690:Excitatory Amino Acid Agonists; D007476:Ionophores; D015759:Ionomycin; D016202:N-Methylaspartate; D011189:Potassium Chloride; D001120:Arginine; D019001:Nitric Oxide Synthase