In vivo production of nitric oxide correlates with NMDA-induced cerebral hyperemia in newborn sheep.
Stimulation of N-methyl-D-aspartate (NMDA) receptors in brain increases nitric oxide production in vitro. We tested the hypothesis that nitric oxide participates in the increase in local cerebral blood flow (CBF) caused by infusion of NMDA in anesthetized newborn sheep. We used the combined hydrogen clearance and microdialysis technique for simultaneous measurement of local CBF, infusion of drugs, and measurement of interstitial levels of L-[14C]citrulline in the parietal cortex. Release of L-[14C]citrulline into the dialysate during continuous infusion of L-[14C]arginine was used as a marker of nitric oxide production in vivo. Citrulline recovery and CBF were measured hourly during a 4-h infusion of cerebrospinal fluid containing either 1) no additional drugs, 2) 1 mM NMDA, 3) 1 mM NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor), 4) 1 mM NMDA + 1 mM L-NAME, 5) 0.1 mM 2-chloroadenosine (adenosine receptor agonist), or 6) 0.1 mM 2-chloroadenosine + 1 mM L-NAME. At 240 min of perfusion, CBF (ml.min-1.100 g-1; means +/- SE) was as follows: control 52 +/- 3, NMDA 116 +/- 11, L-NAME 32 +/- 5, NMDA+L-NAME 40 +/- 4,2-chloroadenosine 201 +/- 63, and 2-chloroadenosine+L-NAME 129 +/- 18. Citrulline recovery (fmol/min) at 240 min of perfusion was as follows: control 38 +/- 12, NMDA 149 +/- 21, L-NAME 9 +/- 1, NMDA+L-NAME 39 +/- 5, 2-chloroadenosine 13 +/- 5, and 2-chloroadenosine+L-NAME 17 +/- 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Northington
F J
FJ
Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Tobin
J R
JR
Koehler
R C
RC
Traystman
R J
RJ
D015762:2-Chloroadenosine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001810:Blood Volume / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002956:Citrulline / Q000378:metabolism; D004338:Drug Combinations; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010296:Parietal Lobe / Q000378:metabolism; D012756:Sheep
D004338:Drug Combinations; D015762:2-Chloroadenosine; D002956:Citrulline; D009569:Nitric Oxide; D016202:N-Methylaspartate; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester