Nitric oxide synthase inhibition with NG-mono-methyl-L-arginine reversibly decreases cerebral blood flow in piglets

Crit Care Med. 1994 Mar;22(3):384-92. doi: 10.1097/00003246-199403000-00006.

Abstract

Objective: We tested the hypothesis that, in piglets, the intravenous administration of the reversible inhibitor of nitric oxide synthase, NG-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 NG-mono-methyl-L-arginine, 100 mg of NG-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 NG-mono-methyl-L-arginine (50 mg dose: 84 +/- 6 to 100 +/- 7 mmHg; 100 mg dose: 82 +/- 4 to 107 +/- 4 mmHg; 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 mmHg/mL/min/100 g; p < .05) only after 100 mg of NG-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 NG-mono-methyl-L-arginine administration. Blood flow returned to control values by 30 mins after infusion. NG-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 NG-mono-methyl-L-arginine was associated with prompt (by 3 mins) recovery of blood flow to all brain regions that were affected by NG-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Analysis of Variance
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / antagonists & inhibitors
  • Arginine / pharmacology
  • Cerebrovascular Circulation / drug effects*
  • Dose-Response Relationship, Drug
  • Infusions, Intravenous
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide Synthase
  • Prospective Studies
  • Random Allocation
  • Swine
  • Time Factors
  • omega-N-Methylarginine

Substances

  • omega-N-Methylarginine
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases