BRAIN-CELL MEMBRANE NA-ATPASE ACTIVITY ALTER INHIBITION OF CEREBRAL NITRIC-OXIDE SYNTHASE BY INTRAVENOUS N-G-NITRO-L-ARGININE IN NEWBORN PIGLETS(,K+)

This study investigated the effects of in vivo inhibition of cerebral nitric oxide synthase by intravenous administration of N-G-nitro-L-arg inine (NNLA) on the cell membrane Na+,K+-ATPase activity in the cerebr al cortex of newborn piglets. NNLA was administered intravenously to 2 2 piglets at doses of 5 mg/kg (n = 3), 25 (n = 3), 50 (n = 4), 75 (n = 4), and 100 mg/kg (n = 2). Control animals (n = 6) received normal sa line only. 90 min after infusion the cerebrum was obtained. The cerebr al nitric oxide synthase activity, determined by measuring the convers ion of [H-3]-L-arginine into [H-3]-L-citrulline in the brain homogenat e, decreased from 9.1 + 2.0 pmol/mg protein/min in controls to 1.7 +/- 0.6 pmol/mg protein/min after the administration of 75 and 100 mg/kg NNLA. The Na+,K+-ATPase activity was measured in the P2 fraction of co rtical tissue homogenate. The Na+,K+-ATPase activity was within the no rmal range (48.3 +/- 4.9 mu mol/mg protein/h) up to 75 mg/kg of NNLA. At a dose of NNLA of 100 mg/kg, the Na+,K+-ATPase activity decreased t o 31.5 +/- 0.7 mu mol/mg protein/h (p < 0.05). Four animals developed hypoxemia and lactic acidosis. The results demonstrate that inhibition of the cerebral nitric oxide synthase activity in vivo in newborn pig lets by intravenous administration of NNLA did not affect the cortical cell membrane Na+,K+-ATPase activity up to a dose of 75 mg/kg. Doses of 100 mg/kg decreased the Na+,K+-ATPase activity, probably by inducin g cerebral hypoxia-ischemia.