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


METHODS
Prospective, randomized, controlled animal study.


METHODS
Animal laboratory at a university.


METHODS
Pentobarbital-anesthetized piglets (1 to 2 wks of age; 2.6 to 4.0 kg).


METHODS
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.


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.
Greenberg
R S
RS
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD.
Helfaer
M A
MA
Kirsch
J R
JR
Moore
L E
LE
Traystman
R J
RJ
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase; D011446:Prospective Studies; D011897:Random Allocation; D013552:Swine; D013997:Time Factors; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases