Nitric oxide synthase inhibition with N(G)-mono-methyl-L-arginine reversibly decreases cerebral blood flow in piglets

R. S. Greenberg, M. A. Helfaer, J. R. Kirsch, L. E. Moore, R. J. Traystman

Research output: Contribution to journalReview article

21 Scopus citations

Abstract

Objective: We tested the hypothesis that, in piglets, the intravenous administration of the reversible inhibitor of nitric oxide synthase, N(G)- mono-methyl-L-arginine, decreases cerebral blood flow via a mechanism unrelated to cerebral oxygen consumption. Design: Prospective, randomized, controlled animal study. Setting: Animal laboratory at a university. Subjects: Pentobarbital-anesthetized piglets (1 to 2 wks of age; 2.6 to 4.0 kg). Interventions: Piglets were treated with either 50 mg of N(G)-mono- methyl-L-arginine, 100 mg of N(G)-mono-methyl-L-arginine, or an equal volume of saline by intravenous infusion over 10 mins. Measurements and Main Results: Mean arterial pressure increased after N(G)-mono-methyl-L-arginine (50 mg dose: 84 ± 6 to 100 ± 7 mm Hg; 100 mg dose: 82 ± 4 to 107 ± 4 mm Hg; p < .001). Forebrain blood flow (microspheres) decreased (37 ± 2 to 30 ± 2 mL/min/100 g; p < .05) and cerebrovascular resistance increased (2.1 ± 0.2 to 3.5 ± 0.3 mm Hg/mL/min/100 g; p < .05) only after 100 mg of N(G)- mono-methyl-L-arginine. Neurohypophysis blood flow decreased to 56 ± 9% of the control value, while forebrain blood flow decreased only to 81 ± 4% of the control value after 100 mg of N(G)-mono-methyl-L-arginine administration. Blood flow returned to control values by 30 mins after infusion. N(G)-mono- methyl-L-arginine administration had no effect on cerebral oxygen consumption at either dose. Intravenous administration of L-arginine (300 mg) immediately after the infusion of 100 mg of N(G)-mono-methyl-L-arginine was associated with prompt (by 3 mins) recovery of blood flow to all brain regions that were affected by N(G)-mono-methyl-L-arginine. Conclusions: These data suggest that nitric oxide and/or a nitric oxide-containing substance is an important mediator of cerebrovascular tone in piglets, acting via a mechanism unrelated to altering cerebral oxygen consumption.

Original languageEnglish (US)
Pages (from-to)384-392
Number of pages9
JournalCritical care medicine
Volume22
Issue number3
DOIs
StatePublished - Jan 1 1994

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Keywords

  • blood gas analysis
  • cerebral blood flow
  • critical illness
  • endothelium-derived relaxant factor
  • microspheres
  • neurologic emergencies
  • nitric oxide
  • oxygen consumption
  • vascular biology
  • vascular resistance

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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