Effects of moderate, central fluid percussion traumatic brain injury on nitric oxide synthase activity in rats.
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.
Alagarsamy
S
S
Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston, USA.
DeWitt
D S
DS
Johnson
K M
KM
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
D018690:Excitatory Amino Acid Agonists; D007476:Ionophores; D015759:Ionomycin; D016202:N-Methylaspartate; D011189:Potassium Chloride; D001120:Arginine; D019001:Nitric Oxide Synthase