Brain cell membrane Na+,K(+)-ATPase activity after inhibition of cerebral nitric oxide synthase by intravenous NG-nitro-L-arginine in newborn piglets.
This study investigated the effects of in vivo inhibition of cerebral nitric oxide synthase by intravenous administration of NG-nitro-L-arginine (NNLA) on the cell membrane Na+,K(+)-ATPase activity in the cerebral cortex of newborn piglets. NNLA was administered intravenously to 22 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 saline only. 90 min after infusion the cerebrum was obtained. The cerebral nitric oxide synthase activity, determined by measuring the conversion of [3H]-L-arginine into [3H]-L-citrulline in the brain homogenate, 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 cortical tissue homogenate. The Na+,K(+)-ATPase activity was within the normal range (48.3 +/- 4.9 mumol/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 to 31.5 +/- 0.7 mumol/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 piglets 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 inducing cerebral hypoxia-ischemia.
Groenendaal
F
F
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, USA.
Mishra
O P
OP
McGowan
J E
JE
Delivoria-Papadopoulos
M
M
D000140:Acidosis, Lactic / Q000139:chemically induced; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006439:Hemodynamics / Q000502:physiology; D000860:Hypoxia / Q000139:chemically induced; D007275:Injections, Intravenous; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase