N omega-nitro-L-arginine influences cerebral metabolism in awake sheep.
Cerebral vasodilation in hypoxia may involve endothelium-derived relaxing factor-nitric oxide (NO). An inhibitor of NO formation, N omega-nitro-L-arginine (LNA, 100 micrograms/kg i.v.), was given to conscious sheep (n = 6) during normoxia and again in hypocapnic hypoxia (arterial PO2 approximately 38 Torr). Blood samples were obtained from the aorta and sagittal sinus, and cerebral blood flow (CBF) was measured with 15-microns radiolabeled microspheres. During normoxia, LNA elevated (P < 0.05) mean arterial pressure from 82 +/- 3 to 88 +/- 2 (SE) mmHg and cerebral perfusion pressure (CPP) from 72 +/- 3 to 79 +/- 3 mmHg, CBF was unchanged, and cerebral lactate release (CLR) rose temporarily from 0.0 +/- 1.9 to 13.3 +/- 8.7 mumol.min-1 x 100 g-1 (P < 0.05). The glucose-O2 index declined (P < 0.05) from 1.67 +/- 0.16 to 1.03 +/- 0.4 mumol.min-1 x 100 g-1. Hypoxia increased CBF from 59.9 +/- 5.4 to 122.5 +/- 17.5 ml.min-1 x 100 g-1 and the glucose-O2 index from 1.75 +/- 0.43 to 2.49 +/- 0.52 mumol.min-1 x 100 g-1 and decreased brain CO2 output, brain respiratory quotient, and CPP (all P < 0.05), while cerebral O2 uptake, CLR, and CPP were unchanged. LNA given during hypoxia decreased CBF to 77.7 +/- 11.8 ml.min-1 x 100 g-1 and cerebral O2 uptake from 154 +/- 22 to 105.2 +/- 12.4 mumol.min-1 x 100 g-1 and further elevated mean arterial pressure to 98 +/- 2 mmHg (all P < 0.05), CLR was unchanged, and, surprisingly, brain CO2 output and respiratory quotient were reduced dramatically to negative values (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, School of Medicine and Biomedical Sciences, University, Buffalo, New York 14214.
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Iwamoto
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Yang
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Yoshinaga
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Krasney
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Krasney
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000097:blood; D019335:Nitroarginine; D010101:Oxygen Consumption / Q000187:drug effects; D012756:Sheep
D001786:Blood Glucose; D007773:Lactates; D002245:Carbon Dioxide; D019335:Nitroarginine; D001120:Arginine; D006162:Guanylate Cyclase